A cross-sectional analysis was performed among patients who have been followed in a large PsA clinic. Demographic, clinical and radiographic data as well as information about quality of life and function were retrieved from the clinic database. Radiographic damage was assessed according to modified Steinbrocker score (mSS). The association between gender and the following outcome variables, radiographic joint damage, axial involvement and measures of quality of life and function, was assessed by multivariate regression analysis after adjustment for potential confounders.

Three hundred and forty-five men and 245 women were included in the study. Axial involvement was more frequent in men (42.9% vs 31%, p=0.003). In multivariate analysis, adjusting for potential confounders, men were more likely to develop axial involvement (OR 1.8, p=0.003). Men were also more likely to develop more severe radiographic damage in the peripheral joints as evident by mSS. Men were more likely to be in a higher mSS damage category compared with women after adjusting for potential confounders in multivariate analysis (OR 1.6, p=0.007). Women suffered from more severe limitations in function and worse quality of life compared with men based on several patients' reported outcomes.

Men with PsA are more likely to develop axial involvement and radiographic joint damage, while women are more likely to report about limitation in function and impaired quality of life.

Women with SLE aged 18–35 years who had stable disease were recruited to receive GARDASIL vaccination and an equal number of age-matched healthy women were also vaccinated. Seroconversion rates of antibodies to HPV serotypes 6, 11, 16 and 18 at months 7 and 12 and adverse events (AEs) were compared between patients and controls. The rate of disease flares in SLE participants was compared with matched SLE controls.

50 patients with SLE and 50 healthy controls were studied. The mean age and disease duration of the patients was 25.8±3.9 years and 6.6±4.5 years, respectively. At month 12 the seroconversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. In patients with SLE there were no significant changes in the titres of anti-dsDNA, complements, anti-C1q and SLE Disease Activity Index scores from baseline to months 2, 7 and 12. There was one mild/moderate SLE flare at months 0–2, two mild/moderate flares at months 3–6 and six mild/moderate and two severe flares at months 7–12. Disease flares in patients with SLE occurred at a similar frequency to that of 50 matched SLE controls (0.22/patient/year vs 0.20/patient/year, p=0.81). Injection site reaction was the commonest AE (5%), and the incidence of AEs was comparable between patients with SLE and controls.

The quadrivalent HPV vaccine is well tolerated and reasonably effective in patients with stable SLE and does not induce an increase in lupus activity or flares.

The 2nd–5th MCP joints of 49 patients with RA were examined by CT and US, and evaluated for the presence of bone erosion in each MCP joint quadrant. On CT, erosion volume was scored according to the OMERACT-RAMRIS score (bone volume loss in 10% increments of original bone volume). US erosions were scored 0–3 according to the Szkudlarek and Scoring by UltraSound Structural erosion (ScUSSe) systems, respectively.

Seven hundred and eighty-four MCP joint quadrants were examined. Erosions were detected by CT in 259 quadrants and by US in 142 quadrants. Sensitivity/specificity/accuracy of US was overall 44%/95%/78% compared with 71%/95%/90% in areas with good US accessibility (radial 2nd MCP, ulnar 5th MCP and all dorsal/palmar aspects). US detected 95% of erosions with bone volume loss >20%. In US accessible areas, 63% of erosions with 1–10% bone volume loss and 94% of erosions with >10% bone loss were detected. The two US scoring systems agreed well on large erosions, whereas the smallest erosions (Szkudlarek grade 1, of which 86% were confirmed by CT) were not scored by ScUSSe.

In accessible areas, US was highly accurate for detection and semiquantitative assessment of RA bone erosion. Even the smallest erosions, only detected in one plane, were generally confirmed by CT.

In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time.

In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (~9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (~9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients.

This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.

CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score–CRP, individual ACR components, as well as soluble bone turnover markers.

CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (–14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (–5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (–5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits.

CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.

A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years.

134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β₂ glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mother's antibodies before 6 months of age (p<0.05).

Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

To evaluate whether LUS is reliable in the screening of ILD in patients with SSc.

Fifty-eight consecutive patients with SSc (54 women, mean age 51±14 years) who underwent a high resolution CT (HRCT) scan of the chest were also evaluated by LUS for detection of B-lines. Of these, 32 patients (29 women, mean age 51±15 years) fulfilled the criteria for a diagnosis of very early SSc.

At HRCT, ILD was detected in 88% of the SSc population and in 41% of the very early SSc population. A significant difference in the number of B-lines was found in patients with and without ILD on HRCT (57±53 vs 9±9; p<0.0001), with a concordance rate of 83%. All discordant cases were false positive at LUS, providing a sensitivity and negative predictive value of 100% in both SSc and very early SSc.

ILD may be detected in patients with very early SSc. The presence of B-lines at LUS examination correlates with ILD at HRCT. LUS is very sensitive for detecting ILD even in patients with a diagnosis of very early SSc. The use of LUS as a screening tool for ILD may be feasible to guide further investigation with HRCT.

The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years.

After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate <60 ml/min and age >65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001). The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS, indicating a better performance of the CVS (p=0.052).

In patients with non-infectious mixed CryoVas, the main prognostic factors are age >65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.

Using joint tissues from 156 patients with OA, and control cartilage from 25 patients who had neck of the femur fractures, the authors measured the overall gene expression by quantitative PCR and the allelic expression of the genes, using an assay that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism.

Five of the genes were expressed in joint tissues, the exception being GPR22, which the authors could not detect. In OA cartilage compared with control cartilage, significantly reduced expression levels were observed for these five genes. Carriers of the OA-associated alleles showed a significant reduction in expression of HBP1 in cartilage (p=0.0002) and synovium (p=0.02), and of DUS4L in fat pad (p=0.04). HBP1 and DUS4L also demonstrated allelic expression imbalance across a range of different joint tissues, with carriers of the associated allele showing an HBP1 allelic expression imbalance profile that was significantly different from non-carriers (p=0.008).

Cis-acting regulatory polymorphisms acting on HBP1 contribute to the OA association signal at chromosome 7q22. HBP1 codes for a transcription factor and studies by the authors have enabled them to prioritise this gene for further investigation.

To evaluate the association between body mass index (BMI) and the risk of PsA among patients with psoriasis from the general population.

The authors conducted a cohort study using data from The Health Improvement Network, an electronic medical records database representative of the UK general population, collected between 1995 and 2010. The exposure of interest was the first BMI measured after psoriasis diagnosis and endpoints were incident cases of physician-diagnosed PsA. The authors estimated the RR of PsA after adjusting for age, sex, and histories of trauma, smoking and alcohol consumption.

Among 75 395 individuals with psoriasis (43% male, mean follow-up of 5 years, and mean age of 52 years), 976 developed PsA (incidence rate, 26.5 per 10 000 person-years). The PsA incidence rates increased with increasing BMI. Compared with psoriasis patients with BMI <25 kg/m², the RRs for developing PsA were 1.09 (0.93–1.28) for BMIs from 25.0 to 29.9, 1.22 (1.02–1.47) for BMIs from 30.0 to 34.9 and 1.48 (1.20–1.81) for BMIs ≥35.0. In our secondary analysis among all individuals, regardless of psoriasis (~2 million), the corresponding multivariate RRs tended to be stronger (1.0, 1.17, 1.57, 1.96; p for trend <0.001).

This general population study suggests that obesity is associated with an increased risk of incident PsA and supports the importance of weight reduction among psoriasis patients who often suffer from the metabolic syndrome and obesity.

Monocytes/monocyte-derived macrophages from healthy volunteers homozygous for either wild type (WT) or 77H CD11b were studied. The genotype-specific expression of CD11b, and CD11b activation using conformation-specific antibodies were measured. Genotype-specific differences in iC3b-mediated phagocytosis, adhesion to a range of ligands and the secretion of cytokines following CR3 ligation were studied. The functionality of R77H was confirmed by replicating findings in COS7 cells expressing variant-specific CD11b.

No genotype-specific difference in CD11b expression or in the expression of CD11b activation epitopes was observed. A 31% reduction was observed in the phagocytosis of iC3b opsonised sheep erythrocytes (sRBC_iC3b) by 77H cells (p=0.003) and reduced adhesion to a range of ligands: notably a 24% reduction in adhesion to iC3b (p=0.014). In transfected COS7 cells, a 42% reduction was observed in phagocytosis by CD11b (77H)-expressing cells (p=0.004). A significant inhibition was seen in the release of Toll-like receptor 7/8-induced pro-inflammatory cytokines from WT monocytes when CR3 was pre-engaged using sRBC_iC3b, but no inhibition in 77H monocytes resulting in a significant difference between genotypes (interleukin (IL)-1β p=0.030; IL-6 p=0.029; tumour necrosis factor alpha p=0.027).

The R77H variant impairs a broad range of CR3 effector functions in human monocytes. This study discusses how perturbation of this pathway may predispose to SLE.

PsA probands, psoriasis probands and their first-degree family members were included. All participants were evaluated for the presence of psoriasis and inflammatory arthritis. HLA-B and -C genotyping was performed. The family-based association test was used to test for differences between PsA and psoriasis patients in transmission of candidate alleles from parents to offspring.

A total of 178 PsA and 30 psoriasis probands and 561 first degree family members were analysed. The following HLA alleles were over-transmitted to PsA compared with psoriasis: HLA-C*12 (p=0.005), HLA-B*38 (p=0.04), HLA-B*39 (p=0.03), HLA-B*27 (p=0.002).

HLA-B*27, HLA-B*38, HLA-B*39 and HLA-C*12 alleles are potential PsA-specific genetic markers among patients with psoriasis.

To examine childhood SES measures, SES trajectory and other perinatal factors in relation to RA.

The sample included 50 884 women, aged 35–74 (84% non-Hispanic white) enrolled 2004–9 in a US national cohort study. In baseline questionnaires, cases (N=424, 0.8%) reported RA diagnosis after age 16, ever use of disease-modifying antirheumatic drugs or steroids for RA and ≥6 weeks bilateral joint swelling. Childhood SES measures are presented as OR and 95% CI adjusted for age and race/ethnicity. Analyses of perinatal factors also adjusted for childhood SES, and joint effects of childhood and adult SES and smoking exposures were evaluated.

Patients with RA reported lower childhood household education (<12 years vs college degree; OR=1.7; 95% CI 1.1 to 2.5), food insecurity (OR=1.5, 95% CI 1.1 to 2.0) and young maternal age (<20 vs 20–34 years; OR=1.7, 95% CI 1.2 to 2.5), with a trend (p<0.0001) for increasing number of adverse factors (OR=3.0; 95% CI 1.3 to 7.0; 4 vs 0 factors) compared with non-cases. High birth weight (>4000 g) and preconception paternal smoking were independently associated with RA. Together, lower childhood SES and adult education (<college degree) were associated with RA (interaction p=0.03), with a joint effect magnitude similar to a history of paternal and adult smoking.

RA was associated with low childhood SES sustained into adulthood, with cumulative effects across multiple measures, suggesting the importance of other unmeasured factors linking SES and RA.

Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)).

82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, –10.7 mm; 95% CI –15.4 to –6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count.

Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

MSC were tested both in an induced (adjuvant-induced) and a spontaneous (K/BxN) arthritis model. Arthritis was assessed clinically and histologically. The proliferation of splenocytes and fibroblast-like synoviocytes (FLS) in the presence of MSC was measured by radioactivity incorporation. Toll-like receptor (TLR) expression was measured by real-time PCR. T-regulatory cell (Treg) frequency, T-cell apoptosis and cytokine secretion were monitored by flow cytometry.

MSC, in vitro, strongly inhibited critical cell populations; splenocytes and FLS. In contrast, MSC proved ineffective in vivo, unless they were administered before disease onset, an effect implying that the inflammatory arthritic milieu potentially abrogates MSC immunomodulatory properties. In order to alleviate inflammation before MSC infusion, the authors administered, at arthritis onset, a short course with a proteasome inhibitor, bortezomib, whereas MSC were infused when established disease was expected. The bortezomib plus MSC group demonstrated a significantly decreased arthritis score over arthritic, MSC-only, bortezomib-only groups, also confirmed by histology and immunohistochemistry. The bortezomib plus MSC combination restored TLR expression and Treg frequency in blood and normalised FLS and splenocyte proliferation, apoptosis and cytokine secretion.

MSC lose their immunomodulatory properties when infused in the inflammatory micromilieu of autoimmune arthritis. Conditioning of the recipient with bortezomib alters the disease microenvironment enabling MSC to modulate arthritis. Should milieu limitations also operate in human disease, this approach could serve as a strategy to treat RA by MSC.

This study examined bone erosions in the metacarpophalangeal joints of 20 patients receiving treatment with the IL-6R blocker tocilizumab using micro CT (µCT). The maximal width and depth of individual bone erosions was measured at baseline and after 1 year of treatment.

133 bone erosions were identified at baseline with a mean (±SD) size of 2.23±1.26 mm and depth of 2.16±1.50 mm. Distribution analysis showed predominant involvement of the second compared with the third and fourth metacarpophalangeal joints, the metacarpal heads compared with the phalangeal bases and the radial quadrants compared with all other surfaces. Repair of bone erosions during tocilizumab treatment was confined to those lesions showing sclerosis at baseline and/or at follow-up and those with a width larger than 1.6 mm. The mean decrease in width of sclerosed erosions was thus 0.14±0.05 mm (p=0.0086) and 0.20±0.08 mm (p=0.019) for sclerosing lesions after 1 year of treatment.

Blockade of IL-6R by tocilizumab can induce limited repair in a subset of erosions, particularly in large lesions with sclerosis. Repair of erosions during tocilizumab treatment reflects the favourable impact of IL-6R blockade on local bone remodelling in patients with RA.

Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon- release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT).

A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease.

LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.

A population-based cohort of parent–offspring triads from Denmark (1977–2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history.

Among 3 513 817 parent–offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6–2.9; p=NS).

The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.

Serum IL-6 and soluble IL-6 receptor levels were measured in patients with SSc (n=68) and healthy controls (n=15). Associations between serum IL-6 level and C reactive protein, platelet count and key clinical outcomes in SSc were explored. Expression of IL-6 in skin biopsies was also examined and western blot and reverse transcription PCRanalysis were performed using cultured dermal fibroblasts. The effect of IL-6 trans-signalling on production of extracellular matrix proteins was assessed and downstream signalling pathways were examined using pharmacological inhibitors.

Serum IL-6 level was frequently elevated in patients with SSc, particularly in those with diffuse cutaneous SSc (dcSSc) with thrombocytosis and elevated acute phase markers. Prominent expression in the skin was observed in dermal fibroblasts, mononuclear cells and endothelial cells in patients with early dcSSc. In vitro experiments supported a potent profibrotic effect of IL-6 trans-signalling via the JAK2/STAT3 and ERK pathways. High IL-6 expression early in dcSSc appears to be associated with more severe skin involvement at 3 years and worse long-term survival than in those without elevated IL-6 levels.

Our results confirm the overexpression of IL-6 in dcSSc and support the potential of IL-6 as a surrogate marker for clinical outcome in this disease. The data also provide rationale for clinical studies targeting IL-6 trans-signalling as a potential antifibrotic therapy for SSc.

Within a cost–utility framework, the base-case analysis estimated the incremental healthcare cost per additional quality-adjusted life year (QALY), using the EQ-5D to generate QALYs, for each risk-defined subgroup. Uncertainty was explored with cost–utility planes and acceptability curves. Sensitivity analyses were performed to consider alternative costing methodologies, including the assessment of societal loss relating to work absence and the incorporation of generic (ie, non-back pain) healthcare utilisation.

The stratified management approach was a cost-effective treatment strategy compared with current best practice within each risk-defined subgroup, exhibiting dominance (greater benefit and lower costs) for medium-risk patients and acceptable incremental cost to utility ratios for low-risk and high-risk patients. The likelihood that stratified care provides a cost-effective use of resources exceeds 90% at willingness-to-pay thresholds of £4000 ( 4500; $6500) per additional QALY for the medium-risk and high-risk groups. Patients receiving stratified care also reported fewer back pain-related days off work in all three subgroups.

Compared with current best practice, stratified primary care management for low back pain provides a highly cost-effective use of resources across all risk-defined subgroups.

Technical details of spinal MRI and the description of spinal lesions of both inflammation and structural changes were discussed in consecutive meetings of 10 experts of the Assessment in SpondyloArthritis international Society (ASAS). The discussions aimed at a broad consensus on definitions of ‘a positive spinal MRI’ for both types of lesions and were backed up by a systematic literature search.

A total of six different types of lesions were described for inflammation—anterior/posterior spondylitis, spondylodiscitis, arthritis of costovertebral joints, arthritis of zygoapophyseal joints and enthesitis of spinal ligaments—and another four for structural changes—fatty deposition, erosions, syndesmophytes and ankylosis. In the literature review, four relevant papers were identified. Anterior/posterior spondylitis and fat depositions at vertebral edges were considered as the most typical findings in SpA. Based on expert consensus and taking the literature review into consideration, a positive spinal MRI for inflammation was defined as the presence of anterior/posterior spondylitis in ≥3 sites. Evidence of fatty deposition at several vertebral corners was found to be suggestive of axial SpA, especially in younger adults. ASAS members (n=56) approved these definitions by voting in January 2010.

This consensus statement gives clear descriptions of disease-related spinal lesions and of definitions of a positive spinal MRI for inflammatory lesions (spondylitis) and structural changes (fat deposition). These definitions can be used to describe findings of spinal MRI in patients with SpA in daily practice and clinical studies.

6261 sets of hands and feet x-rays of 2193 RA patients from Leiden, Groningen (both from The Netherlands) and North America were studied. Correlations between joint damage at different regions were compared (unilateral vs bilateral and hands vs feet). Analyses were done at single time points (cross-sectional) and for progression over time (longitudinal), both for continuous severity measures (Sharp/van der Heijde score; SHS) and binomial measures of erosiveness.

When studying single time points, the severity of joint damage (SHS) is highly correlated between left and right, but weakly correlated between hands and feet. Correlation coefficients were higher in advanced than early RA. These findings were comparable in the three datasets. When evaluating erosiveness using only unilateral x-rays or hands without feet, 19.3% and 24.0–40.4% are incorrectly classified as non-erosiveness. Similarly, when evaluating disease progression by imaging only unilateral x-rays or only hand x-rays, progression would have been missed in 11.6–16.2% and 21.2–31.0% of patients.

Performing x-rays of both hands and feet yields additive information compared with imaging only a part of these.

Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY^– sex chromosome complement, with each genotype being ovary bearing.

Mice with XX sex chromosome complement compared with XY^– exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice.

These data show that the XX sex chromosome complement, compared with XY^–, is associated with accelerated spontaneous lupus.

DIP and PIP joints were obtained from post mortem specimens (n=40). Plain x-rays of the DIP and PIP joints were taken and radiographic OA was determined by the Kellgren and Lawrence classification. Individual radiographic features were scored according to the method described by Altman. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. Spearman's correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups (bony swelling vs no bony swelling) were determined by Student t test.

A highly significant correlation was found between histological (Mankin score) and radiographic (Kellgren/Lawrence score) changes in the investigated DIP (r_s=0.87, p<0.0001) and PIP (r_s=0.79, p<0.0001) joints. A subgroup of patients (37.5% for DIP and 18.8% for PIP joints) showed advanced radiographic changes (Kellgren/Lawrence score ≥2) in joints without clinical bony swelling. Histologically, the mean Mankin scores accounted for 11±1.66 for DIP and 9.67±2.4 for PIP joints.

On the basis of histopathological changes of DIP and PIP joints, this investigation demonstrates the validity of x-ray examinations and supports the use of plain radiography in the diagnosis of hand OA and in the classification of hand OA in clinical trials.

113 children carrying MEFV mutations (44 with mutations in two alleles, 69 heterozygous) and 205 children negative for mutations in genes associated with periodic fevers were analysed. The following groups of patients were considered: patients carrying two high penetrance mutations (M694V, M694I, M680I); one high, one low penetrance mutation; two low penetrance mutations; one high penetrance mutation; one low penetrance mutation; genetically negative patients.

Patients with two MEFV mutations displayed a shorter duration of fever attacks and higher prevalence of a positive family history than patients carrying one MEFV mutation and genetically negative patients. Severe abdominal pain, chest pain and pleurisy were also more frequent in patients with two MEFV mutations compared with children with one MEFV mutation and genetically negative patients. Conversely, a higher frequency of exudative and erythematous pharyngitis, enlargement of cervical lymph nodes, aphthous stomatitis and non-specific skin rash was observed in genetically negative patients and, to a lesser extent, in patients with one MEFV mutation. The frequency of ‘familial Mediterranean fever (FMF)-like symptoms’ decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with an opposite trend for ‘periodic fever, aphthous stomatitis, pharyngitis, adenitis-like symptoms’.

This clinical observation supports recent findings contrasting the notion of FMF being a pure autosomal recessive disorder associated with recurrence of mutations leading to loss of protein function. A dosage effect could be invoked, giving rise to symptom onset even in the presence of one wild-type allele.

A total of 149 randomly selected subjects (mean 63 years, range 52–78; 46% female) was studied. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF–α) and interleukin (IL)-6 were measured at baseline and 2.7 years later. Knee pain was recorded using the Western Ontario and McMasters osteoarthritis index questionnaire at baseline and 5 years later. Knee radiographic osteoarthritis of both knees was assessed at baseline, and knee bone marrow lesions, joint effusion and cartilage defects were determined using T1 or T2-weighted fat saturated MRI.

After adjustment for confounding variables, baseline hs-CRP was positively associated with change in total knee pain (β=0.33 per mg/l, p=0.032), as well as change in the pain at night in bed (β=0.12 per ml/pg, p=0.010) and while sitting/lying (β=0.12 per ml/pg, p=0.002). Change in hs-CRP was also associated with change in knee pain at night and when sitting/lying (both p<0.05). Baseline TNFα and IL-6 were associated with change in pain while standing (β=0.06 per ml/pg, p=0.033; β=0.16 per ml/pg, p=0.035, respectively), and change in TNFα was positively associated with change in total knee pain (β=0.66 ml/pg, p=0.020) and change in pain while standing (β=0.26 ml/pg, p=0.002). Adjustment for radiographic osteoarthritis or MRI-detected structural abnormalities led to no or minor attenuation of these associations.

Systemic inflammation is an independent predictor of worsening knee pain over 5 years.

A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed.

At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47–48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria.

In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.

Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) organ domain scores.

At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA–SLEDAI, and immunological by SELENA–SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA–SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA–SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA–SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains.

Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.

In a cohort of 183 JIA patients, clinical variables and single nucleotide polymorphisms (SNPs) in genes involved in the mechanism of action of MTX were determined at the start of MTX treatment. These variables were used to construct a prediction model for non-response to MTX treatment during the first year of treatment. Non-response to MTX was defined according the American College of Rheumatology paediatric 70 criteria. The prediction model was validated in a cohort of 104 JIA patients.

The prediction model included: erythrocyte sedimentation rate and SNPs in genes coding for methionine synthase reductase, multidrug resistance 1 (MDR-1/ABCB1), multidrug resistance protein 1 (MRP-1/ABCC1) and proton-coupled folate transporter (PCFT). The area under the receiver operating characteristics curve (AUC) was 0.72 (95% CI: 0.63 to 0.81). In the validation cohort, the AUC was 0.65 (95% CI: 0.54 to 0.77). The prediction model was transformed into a total risk score (range 0–11). At a cut-off of ≥3, sensitivity was 78%, specificity 49%, positive predictive value was 83% and negative predictive value 41%.

The prediction model that we developed and validated combines clinical and genetic variables to identify JIA patients not responding to MTX treatment. This model could assist clinicians in making individualised treatment decisions.

A web-based registry collecting baseline and clinical information on autoinflammatory diseases and related conditions is available in the member area of the PRINTO web-site. Anonymised data were collected with standardised forms.

1880 (M:F=916:964) individuals from 67 centers in 31 countries have been entered in the Eurofever registry. Most of the patients (1388; 74%), reside in western Europe, 294 (16%) in the eastern and southern Mediterranean region (Turkey, Israel, North Africa), 106 (6%) in eastern Europe, 54 in Asia, 27 in South America and 11 in Australia. In total 1049 patients with a clinical diagnosis of a monogenic autoinflammatory diseases have been enrolled; genetic analysis was performed in 993 patients (95%): 703 patients have genetically confirmed disease and 197 patients are heterozygous carriers of mutations in genes that are mutated in patients with recessively inherited autoinflammatory diseases. The median diagnosis delay was 7.3 years (range 0.3–76), with a clear reduction in patients born after the identification of the first gene associated with autoinflammatory diseases in 1997.

A shared online registry for patients with autoinflammatory diseases is available and enrollment is ongoing. Currently, there are data available for analysis on clinical presentation, disease course, and response to treatment, and to perform large scale comparative studies between different conditions.

The peptide used is a heat shock protein 60 epitope (p1) that elicits tolerogenic peptide-specific immune responses in human arthritis patients and was recently shown to have protective capacity as a bystander antigen in the rat adjuvant arthritis model. Rats were treated with three nasal doses of p1, CpG or a combination of p1 and CpG. Antigen-presenting cells were studied in nose-draining lymph nodes (mandibular lymph nodes; MLN) after nasal treatment, and T-cell responses were analysed in joint-draining lymph nodes after arthritis induction.

Nasal co-administration of p1/CpG significantly augmented the arthritis-protective effect of p1, while CpG treatment alone did not. Co-treatment of p1/CpG increased both the number and activation status of pDC in draining MLN, which was accompanied by amplified p1-specific T-cell proliferation and interleukin (IL)-10 production. During early arthritis, p1-specific IL-10 production was identified at the site of inflammation. P1 and p1/CpG-treated rats showed a greater amount of CD4+FoxP3+ regulatory T cells in the joint-draining lymph nodes, which correlated with lower arthritis scores.

These clinical and immunological data suggest the use of CpG as a potent adjuvant for mucosal peptide-specific immune therapy in arthritis.

89 049 participants were included from the Nurses Health Study II over a 14-year period (1991–2005). Information on body mass index (BMI), weight change and measures of central obesity (waist circumference, hip circumference and waist–hip ratio) was collected during the follow-up. The incidence of clinician-diagnosed PsA was ascertained and confirmed by supplementary questionnaires.

146 incident PsA cases were identified during 1 231 693 person-years of follow-up. Among all participants, BMI was monotonically associated with an increased risk of incident PsA. Compared with BMI less than 25.0, the RR was 1.83 for BMI 25.0–29.9 (95% CI 1.15 to 2.89), 3.12 for BMI 30.0–34.9 (95% CI 1.90 to 5.11) and 6.46 for BMI over 35.0 (95% CI 4.11 to 10.16). There was a graded positive association between weight change from age 18 years, measures of central obesity and risk of PsA (p for trend <0.001). The analysis among participants developing psoriasis during follow-up revealed a similar association (p for trend <0.01), indicating an increased risk of PsA associated with obesity among patients with psoriasis.

This study provides further evidence linking obesity with the risk of incident PsA among US women.

Using PAR₂ gene deletion and other approaches to inhibit or prevent PAR₂ activation, the development and progression of CIA were assessed via clinical and histological scores together with ex vivo immune analyses.

The progression of CIA, assessed by arthritic score and histological assessment of joint damage, was significantly (p<0.0001) abrogated in PAR₂ deficient mice or in wild-type mice administered either a PAR₂ antagonist (ENMD-1068) or a PAR₂ neutralising antibody (SAM11). Lymph node derived cell suspensions from PAR₂ deficient mice were found to produce significantly less interleukin (IL)-17 and IFN in ex vivo recall collagen stimulation assays compared with wild-type littermates. In addition, substantial inhibition of TNFα, IL-6, IL-1β and IL-12 along with GM-CSF and MIP-1α was observed. However, spleen and lymph node histology did not differ between groups nor was any difference detected in draining lymph node cell subsets. Anticollagen antibody titres were significantly lower in PAR₂ deficient mice.

These data support an important role for PAR₂ in the pathogenesis of CIA and suggest an immunomodulatory role for this receptor in an adaptive model of inflammatory arthritis. PAR₂ antagonism may offer future potential for the management of inflammatory arthritides in which a proteinase rich environment prevails.

A detailed document reporting on a qualitative analysis of interviews of patients with knee OA was sent to experts and a Delphi procedure was adopted for item generation. Eighty physicians (64 general practitioners, 16 rheumatologists) recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. The reliability of the questionnaire was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and the Bland–Altman technique.

Sixty items were extracted from analysis of the interview data. The experts needed three Delphi rounds to obtain consensus on a 33-item provisional questionnaire. The item reduction process resulted in an 18-item questionnaire. Exploratory factor analysis extracted three main factors: factor 1 represented expectations for education, factor 2 expectations for information on technical and human support, and factor 3 expectations for physician empathy. The Cronbach α coefficient was 0.91 (95% CI 0.89 to 0.92). Expected divergent validity was observed. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good with an ICC of 0.79, and Bland–Altman analysis did not reveal a systematic trend.

A new 18-item questionnaire assessing patient expectations of management of knee OA by their physicians is proposed. The questionnaire has good content and construct validity.

In this population-based study involving participants aged 55 years and older (Rotterdam Study I), men (n=2372) and women (n=3278) were analysed separately. x-Rays of the knee, hip and hand were scored using the Kellgren and Lawrence score for osteoarthritis at baseline, after 6.6 years and 10 years. Measures of atherosclerosis (carotid intima media thickness (IMT) and carotid plaque) and data on covariates (age, body mass index, hypertension, cholesterol ratio, diabetes mellitus and smoking) were collected at baseline. Multivariate logistic regression models with generalised estimated equations were used to calculate OR and corresponding 95% CI. Secondary multiple comparison adjustment resulted in a significance level of p<0.0021.

In women, IMT showed an independent association with the prevalence of knee osteoarthritis (adjusted OR (aOR) 1.7, 1.1 to 2.7), and carotid plaque with distal interphalangeal (DIP) osteoarthritis (aOR 1.4, 1.2 to 1.7) and with metacarpophalangeal osteoarthritis (aOR 1.5, 1.1 to 2.2). An independent association for IMT with progression of metacarpophalangeal osteoarthritis was found in women (aOR 2.9, 1.18 to 6.93). Additional adjustment for multiple testing yielded a significant association between carotid plaque and DIP osteoarthritis in women (p<0.001).

This study showed independent associations of atherosclerosis with osteoarthritis of the knee and hand joints in women. The evidence was most solid for a relation with DIP osteoarthritis. More research is needed to confirm the associations and examine the differential association with various joints.

To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period.

94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1–≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years).

ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853–82 437) vs median 2454 AU/ml, IQR 449–7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011).

In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.

Peripheral blood mononuclear cells from 13 primary SS patients were obtained at baseline and after 24 weeks of leflunomide treatment. Ex-vivo production of interleukin (IL) 1β and tumour necrosis factor α (TNFα) and of interferon (IFN), IL-4, as well as TNFα ELISA measured production on T-cell and monocyte stimulation. In addition, the authors investigated the ability of leflunomide to influence systemic levels of inflammatory cytokines, as well as T-cell activation markers and the expression of IL-7 receptor α by flow cytometry. Correlations between changes in cytokine levels and changes in clinical response parameters were studied.

Ex-vivo production of IL-1β and TNFα was decreased at 24 weeks in the whole patient group, whereas IFN and IL-4 production were not significantly changed. However, a significant decrease in T-cell-stimulated IFN and TNFα production was observed in clinical responders, but not in non-responders. Moreover, significant correlations were found between increased sialometry values and decreased IFN and TNFα production. In addition, leflunomide reduced levels of inflammatory serum cytokines and CD40L expression, whereas it upregulated IL-7Rα expression on CD4 T cells with persistent serum IL-7 concentrations.

Leflunomide treatment suppressed cytokine release from circulating immune cells. Inhibition of T-helper 1 cell cytokine production was related to clinical efficacy. This suggests that selective T-cell targeting might be a relevant therapeutic strategy in primary SS, possibly enhancing clinical efficacy and safety.

The authors conducted a prospective population-based cohort study. The ESPOIR cohort was a French cohort of 813 patients with early arthritis not receiving disease-modifying antirheumatic drugs (DMARDs). Adherence to the 2007 EULAR recommendations was defined by measuring adherence to three of the recommendations concerning the initiation and early adjustment of DMARDs. The study endpoints were radiographic progression, defined as the presence of at least one new erosion between baseline and 1 year, and disability as a heath assessment questionnaire score ≥1 at 2 years. A propensity score of being treated according to the recommendations was developed.

After adjustment for propensity score, treatment centre and the main confounding factors, patients without recommendation adherence were at increased risk of radiographic progression at 1 year, and of functional impairment at 2 years (OR 1.98, (95% CI: 1.08 to 3.62 and OR: 2.36, (95% CI: 1.17 to 4.67), respectively).

Early arthritis patients whose treatment adhered to the 2007 EULAR recommendations seemed to benefit from such treatment in terms of risk of clinical and radiographic progression. Using a propensity score of being treated according to recommendations in observational studies may be useful in assessing the potential impact of these recommendations on outcome.

Post-hoc analyses were performed in a randomized trial comparing continuous and on-demand NSAID treatment. Relevant high/elevated subgroups were created based on time-averaged (ta) CRP (>5mg/L), ta-ESR (>12mm/hr), ta-BASDAI (>4), ta-ASDAS-CRP (>2.1) and ta-ASDAS-ESR (>2.1). Subgroups were further split according to NSAID-use (continuous vs. on-demand). Radiological progression was presented in probability plots. Statistical interactions were tested using multiple and logistic regression analysis. Differences in radiological progression were analysed using the Chi-square and Mann-Whitney U test.

150 participants randomized to either the continuous-treatment group (n=76), or the on-demand group (n=74) had complete radiographs and were included. The effect of slowing radiological progression with continuous NSAID therapy was more pronounced in patients with elevated ta-CRP-levels, elevated ta-ESR, high ta-ASDAS-CRP or high ta-ASDAS-ESR versus patients with low/normal values. No such effect was found for participants with high vs. low BASDAI. Also, in participants with elevated ta-ESR (irrespective of treatment), there appeared to be a higher rate of structural progression than in participants with normal ta-ESR. Regression analyses showed that continuous NSAID treatment neutralizes the negative effect of inflammation (high ta-ESR).

Patients with elevated acute phase reactants seem to benefit most from continuous treatment with NSAIDs. Continuous NSAID-therapy in patients with elevated acute phase reactants may lead to an improved benefit-risk-ratio of these drugs.

miR expression in SF from TghuTNF and wild-type (WT) control mice were determined by miR deep sequencing (miR-seq) and the arthritic profile was established by pairwise comparisons. Quantitative PCR analysis was utilised for profile validation, miR and gene quantitation in patient SF. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms and validated using gain-of-function coupled with reporter assay experiments.

miR-seq demonstrated that TghuTNF-SF exhibit a distinct pathogenic profile with 22 significantly upregulated and 30 significantly downregulated miR. Validation assays confirmed the dysregulation of miR-223, miR-146a and miR-155 previously associated with human rheumatoid arthritis (RA) pathology, as well as that of miR-221/222 and miR-323-3p. Notably, the latter were also found significantly upregulated in patient RA SF, suggesting for the first time their association with RA pathology. Bioinformatic analysis suggested Wnt/cadherin signalling as a putative pathway target. miR-323-3p overexpression was shown to enhance Wnt pathway activation and decrease the levels of its predicted target β-transducin repeat containing, an inhibitor of β-catenin.

Using miR-seq-based profiling in SF from the TghuTNF mouse model and validations in RA patient biopsies, the authors identified miR-221/222 and miR-323-3p as novel dysregulated miR in RA SF. Furthermore, the authors show that miR-323-3p is a positive regulator of WNT/cadherin signalling in RA SF suggesting its potential pathogenic involvement and future use as a therapeutic target in RA.

Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28–erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage.

Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28–ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant–Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively.

No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.

Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis.

COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009).

Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity.

MRI scans were performed at baseline, 12 and 52 weeks in 76 ankylosing spondylitis patients recruited to a placebo-controlled trial of adalimumab therapy. New syndesmophytes were assessed on lateral radiographs of the cervical and lumbar spine at baseline and 104 weeks. Anonymised MRI scans were read independently by two readers who recorded the presence/absence of acute (type A) and advanced (type B) vertebral corner inflammatory lesions (CIL) and fat lesions. The authors used generalised linear latent and mixed models analysis to adjust for the extent of syndesmophytes/ankylosis at baseline.

New syndesmophytes developed significantly more frequently from type B CIL (16.7%) compared with type A CIL (2.9%) (p=0.002) or no CIL (2.5%) (p<0.0001). This was also observed for both baseline and new vertebral corner fat lesions evolving over 52 weeks (11.1% (p<0.001) and 6.8% (p=0.03), respectively). The association with type B CIL (OR (95% CI 3.88, 1.20 to –12.57) and fat (OR 95% CI 4.83, 2.38– to 9.80), p<0.0001) was significant after adjustment for the extent of syndesmophytes/ankylosis at baseline.

Our data supports the hypothesis that new bone formation is more likely in advanced inflammatory lesions and proceeds through a process of fat metaplasia, supporting a window of opportunity for disease modification.

Ankle joint mRNA and protein expression of AnxA1 and its receptors were analysed in naive and arthritic mice by real-time PCR and immunohistochemistry. Inflammatory arthritis was induced with the K/BxN arthritogenic serum in AnxA1^+/+ and AnxA1^–/– mice; in some experiments, animals were treated with dexamethasone (Dex) or with human recombinant AnxA1 or a protease-resistant mutant (termed SuperAnxA1). Readouts were arthritic score, disease incidence, paw oedema and histopathology, together with pro-inflammatory gene expression.

All elements of the AnxA1 pathway could be detected in naive joints, with augmentation during ongoing disease, due to the infiltration of immune cells. No difference in arthritis intensity of profile could be observed between AnxA1^+/+ and AnxA1^–/– mice. Treatment of mice with Dex (10 µg intraperitoneally daily from day 2) afforded potent antiarthritic effects highly attenuated in the knockouts: macroscopic changes were mirrored by histopathological findings and pro-inflammatory gene (eg, Nos2) expression. Presence of proteinase 3 mRNA in the arthritic joints led the authors to test AnxA1 and the mutant SuperAnxA1 (1 µg intraperitoneally daily in both cases from day 2), with the latter one being able to accelerate the resolving phase of the disease.

AnxA1 is an endogenous determinant for the therapeutic efficacy of Dex in inflammatory arthritis. Such an effect can be partially mimicked by application of SuperAnxA1 which may represent the starting point for novel antiarthritic therapeutic strategies.

In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed.

MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p<0.001) and ACR50 (22% vs 10%, p<0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p<0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28) (p<0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p<0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%).

Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms.

NCT00650078

1032 patients with active RA were randomly assigned 1:1 to ADA+MTX or placebo plus methotrexate (PBO+MTX) for 26 weeks. Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP) <3.2 at weeks 22 and 26. Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission.

Among patients completing 6 months, 44% (207/466) ADA+MTX versus 24% (112/460) PBO+MTX patients achieved stable LDA at weeks 22 and 26 (p<0.001). Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses, more clinical remissions, greater mean reductions in DAS28(CRP), no radiographic progression, and normal functional status at week 26 (p<0.001 for all). The only factor predicting stable LDA was disease activity at week 12. Patients achieving ACR/EULAR remission, particularly in the PBO+MTX group, had some advantage in radiographic outcomes compared with patients who only achieved LDA (but not remission). The overall frequency of adverse events was comparable between groups. There were more serious infections and deaths in the ADA+MTX group, with a possible age effect.

Treatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical, radiographic and functional outcomes in patients with early active RA. Before initiating treatment with adalimumab, individual patient evaluation of the benefit/risk ratio should be carefully considered.

To analyse the long-term safety of adalimumab treatment.

This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data.

The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population.

Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.

To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort.

126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society.

All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years' follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p<0.01).

Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.

A longitudinal study of two independent cohorts (cohort 1, n=24; cohort 2, n=19) of patients with RA treated with anti-TNFα biological agents was carried out to assess their Th17/IL-17 levels before and after the start of anti-TNFα therapy. IL-12/23p40 production was assessed in plasma Peripheral blood lymphocytes (PBLs) and monocytes. Mice with collagen-induced arthritis (CIA) were treated with anti-TNFα alone, anti-IL17 alone or a combination of the two. Efficacy of treatment and response was assessed from changes in Disease Activity Score 28–erythrocyte sedimentation rate scores in patients, and in clinical scores and histological analysis in CIA.

Significant increases in circulating Th17 cells were observed in patients after anti-TNFα therapy and this was accompanied by increased production of IL-12/23p40. There was an inverse relationship between baseline Th17 levels and the subsequent response of patients with RA to anti-TNFα therapy. In addition, PBLs from non-responder patients showed evidence of increased IL-17 production. Similarly, in anti-TNFα-treated mice, there was a strong correlation between IL-17 production and clinical score. Finally combined blockade of TNFα and IL-17 in CIA was more effective than monotherapy, particularly with respect to the duration of the therapeutic effect.

These findings, which need to be confirmed in a larger cohort, suggest that a Th17-targeted therapeutic approach may be useful for anti-TNFα non-responder patients or as an adjunct to anti-TNFα therapy, provided that safety concerns can be addressed.

In MOST, a prospective study of persons at risk of or with knee osteoarthritis, baseline full-limb x-rays and baseline and 30-month MRI were acquired. In knees with normal baseline cartilage morphology in all tibiofemoral subregions, logistic regression was used with generalised estimating equations to examine the association between alignment and incident cartilage damage adjusting for age, gender, body mass index, laxity, meniscal tear and extrusion.

Of 1881 knees, 293 from 256 persons met the criteria. Varus versus non-varus was associated with incident medial damage (adjusted OR 3.59, 95% CI 1.59 to 8.10), as was varus versus neutral, with evidence of a dose effect (adjusted OR 1.38/1° varus, 95% CI 1.19 to 1.59). The findings held even excluding knees with medial meniscal damage. Valgus was not associated with incident lateral damage. Varus and valgus were associated with a reduced risk of incident lateral and medial damage, respectively.

In knees with normal cartilage morphology, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment. These results support that varus increases the risk of the initial development of knee osteoarthritis.

In the Boston OA of the Knee, Framingham OA and Multicenter OA studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥2 (any cartilage defect), ≥3 (areas of partial thickness loss), ≥4 (diffuse partial thickness loss) and ≥5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (<–2°), neutral (-2° to 2°) and valgus (>2°) knees were identified.

The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥4 or ≥5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus alignment, the prevalence of lateral PF cartilage damage equalled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.

Medial PF cartilage damage is at least as prevalent within these older adult populations as lateral PF cartilage damage.

Conventional radiographs (x-rays) of hands and wrists were obtained ~2 years before start (prebaseline), at baseline and ~2 years after start (follow-up) of TNF-I. Clinical data were obtained from the DANBIO registry and the patient files. x-Rays were scored blinded to chronology according to the Sharp/van der Heijde method. Annual radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated.

517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21–86), median disease duration 5 years (range 0–57)) were included. Patients were treated with infliximab (61%), etanercept (15%) or adalimumab (24%). During the DMARD period 85% of patients received methotrexate, 51% sulphasalazine and 78% prednisolone. The median DMARD period was 733 days (IQR 484–1002) and the median TNF-I period was 562 days (IQR 405–766). The median radiographic progression rate decreased from 0.7 (IQR 0–2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0–0.9) units/year in the TNF-I period (p<0.0001, Wilcoxon). Corresponding mean dTSS values were 2.1 (SD 3.7) versus 0.7 (SD 2.3) units/year (p<0.0001, paired t test). 305 patients progressed (dTSS >0) in the DMARD period compared with 158 patients in the TNF-I period (p<0.0001, ²).

This nationwide observational study of RA patients documented significantly reduced radiographic progression during TNF-I treatment compared with the previous period of DMARD treatment.

To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce.

The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007–2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature.

(1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems.

This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lin's coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using statistics.

Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of –4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95–0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement ( statistics 0.75–0.84) in RA activity state classification for all three indices.

PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.

Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit.

Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression.

Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

Total RNA was isolated from highly purified peripheral blood CD4 T cells of 173 early arthritis clinic patients. Paired serum samples were also stored. Microarray analysis of RNA samples was performed and differential transcript expression among 111 ‘training cohort’ patients confirmed using real-time quantitative PCR. Machine learning approaches tested the utility of a classification model among an independent validation cohort presenting with UA (62 patients). Cytokine measurements were performed using a highly sensitive electrochemiluminescence detection system.

A 12-gene transcriptional ‘signature’ identified RA patients in the training cohort and predicted the subsequent development of RA among UA patients in the validation cohort (sensitivity 68%, specificity 70%). STAT3-inducible genes were over-represented in the signature, particularly in anti-citrullinated peptide antibody-negative disease, providing a risk metric of similar predictive value to the Leiden score in seronegative UA (sensitivity 85%, specificity 75%). Baseline levels of serum interleukin 6 (IL-6) (which signals via STAT3) were highest in anti-citrullinated peptide antibodies-negative RA and distinguished this subgroup from non-RA inflammatory synovitis (corrected p<0.05).Paired serum IL-6 measurements correlated strongly with STAT3-inducible gene expression.

The authors have identified IL-6-mediated STAT-3 signalling in CD4 T cells during the earliest clinical phase of RA, which is most prominent in seronegative disease. While highlighting potential biomarker(s) for early RA, the role of this pathway in disease pathogenesis awaits clarification.

A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses.

The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)).

A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.

Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay.

In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes.

The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.

IL-17A and tumour necrosis factor α (TNFα)-induced messenger RNA expression in RA synoviocytes was analysed using Affymetrix U133A microarrays. The capacity of IL-17 alone or in combination with TNFα to induce synoviocyte migration and invasion was tested using Boyden and transwell Matrigel invasion chambers. A functional DNA binding assay was used to evaluate the regulation of the key hypoxia-related gene hypoxia-inducible factor 1 (HIF-1α) expression and activation. The role of metalloproteinase 2 (MMP2) in IL-17-induced invasiveness was assessed using small interfering RNA. Hypoxia pathway gene expression was measured in the blood of RA patients and healthy volunteers using Affymetrix microarrays.

Among the genes induced by IL-17A in RA synoviocytes, a molecular pattern of inflammation hypoxia-related genes, including CXC chemokine receptor 4 (CXCR4) and MMP2 was identified. Using immunofluorescence microscopy, the expression of CXCR4 was confirmed on synoviocytes. IL-17A and TNFα induced synoviocyte migration and invasion through a CXCR4-dependent mechanism with a synergistic effect. Their combination activated HIF-1α through the nuclear factor B pathway. IL-17 enhanced invasion through MMP2 induction as demonstrated using siRNA. Finally, hypoxia genes were overexpressed in the blood of RA patients.

IL-17A, specifically when combined with TNFα may contribute to the progression of RA, notably through their effect on synoviocyte aggressiveness. Part of this effect results from activation of the CXCR4/stromal cell-derived factor 1 and hypoxia-mediated pathways.

Patients from the BeSt cohort were used. RRP was defined as an increase of ≥5 points in the Sharp/van der Heijde score (SHS) in year 1. Functional ability over 8 years, measured with the health assessment questionnaire (HAQ), was compared for patients with and without RRP using linear mixed models. Joint damage progression from years 1 to 8 was compared using logistic regression analyses.

RRP was observed in 102/465 patients. Over 8 years, patients with RRP had worse functional ability: difference in HAQ score 0.21 (0.14 after adjustment for disease activity score (over time)). RRP was associated with joint damage progression ≥25 points in SHS in years 1–8: OR 4.6.

RRP in year 1 is a predictor of worse functional ability over 8 years, independent of baseline joint damage and disease activity. Patients with RRP have more joint damage progression in subsequent years. RRP is thus a relevant outcome on which to base the initial treatment decision.

Medline, EMBASE and the Cochrane library were searched from January 1966 to April 2011 for English language articles on data concerning cardiovascular diseases and cardiovascular risk factors in PsA. Review articles, case reports and studies on psoriasis alone were excluded.

Twenty-eight articles were included in this review. Studies on all-cause mortality revealed mixed results. Available data on cardiovascular disease appeared more consistent, indicating an increased cardiovascular mortality and morbidity in PsA. Commensurate with this, surrogate markers of subclinical atherosclerosis, arterial stiffness and cardiovascular risk factors, for example hypertension, dyslipidaemia, obesity and metabolic-related factors, were more prominent in PsA compared with controls. Suppression of inflammation was linked with a favourable effect on cardiovascular surrogate markers, for example carotid intima media thickness and endothelial dysfunction, in several (un)controlled studies.

Most studies point towards an increased cardiovascular risk in PsA, broadly on a par with the risk level in rheumatoid arthritis, emphasising the need for similar cardiovascular risk management in both conditions. Further studies are needed to indicate whether inflammatory suppression or modification of traditional cardiovascular risk factors, or both, will reduce cardiovascular risk.

A cross-sectional study of the prevalence of CHD and cardiovascular risk factors in participants in the Australian Scleroderma Cohort Study was performed. Controls were drawn from the 2007–8 National Health Survey (NHS) and the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). OR and 95% CI were calculated to determine the prevalence of CHD and cardiovascular risk factors in SSc patients compared with controls.

Data were available for 850 SSc patients (86% female), 15 787 NHS participants (53% female) and 8802 AusDiab participants (56% female). Adjusted for age and gender, the OR of CHD in SSc patients was 1.9 (95% CI 1.4 to 2.4) compared with controls from AusDiab and 2.0 (95% CI 1.5 to 2.5) compared with controls from the NHS. The OR of CHD increased to 3.2 (95% CI 2.3 to 4.5) for SSc patients compared with controls from AusDiab after further adjustment for cardiovascular risk factors. Hypercholesterolaemia, diabetes mellitus and obesity were significantly less prevalent in the SSc cohort than in AusDiab. Within the SSc cohort, the presence of pulmonary arterial hypertension was associated with CHD.

This is the first report of an increased prevalence of CHD in SSc patients. Further studies are required to determine the relative contribution of scleroderma-specific factors such as microvascular disease to the development of CHD.

Lung sections of Fra-2 transgenic (n=12) and wild-type mice (n=6) were analysed at 16 weeks by histology using Dana Point criteria. Cellular and molecular key players were assessed by immunohistochemistry. To test the model's sensitivity to change over treatment, a subgroup of Fra-2 transgenic mice (n=6) was treated with the tyrosine kinase inhibitor nilotinib twice daily 37.5 mg orally from 8 weeks of age.

Fra-2 transgenic mice developed severe vascular remodelling of pulmonary arteries and non-specific interstitial pneumonia-like interstitial lung disease resembling human systemic sclerosis-associated pulmonary hypertension. Histological features typical for systemic sclerosis-associated pulmonary arterial hypertension, such as intimal thickening with concentric laminar lesions, medial hypertrophy, perivascular inflammatory infiltrates, adventitial fibrosis, but not pulmonary occlusive venopathy were frequently detected. Platelet-derived growth factor signalling pathways were activated in pulmonary vessels of Fra-2 transgenic compared with wild-type mice. Since treatment with nilotinib strongly prevented the development of proliferative vasculopathy and lung fibrosis, the model proved to be sensitive to treatment.

This study suggests that Fra-2 transgenic mice as an animal model of systemic sclerosis-associated pulmonary arterial hypertension display main characteristic features of the human disease. It therefore allows studying pathophysiological aspects and might serve as a preclinical model for interventional proof-of-concept studies.

To systematically compare the clinical, laboratory and imaging data of patients with axSpA with respect to their BASDAI level.

A total of 100 consecutive patients with axSpA who had never been treated with TNF blockers were included. Laboratory parameters, spinal MRI and x-rays were quantified. Data were stratified according to BASDAI ≥4.

44 patients were diagnosed as non-radiographic axSpA (nraxSpA) and 56 patients as ankylosing spondylitis (AS): median age 40.3±10.4 years; 57% male, mean disease duration since diagnosis 6.4±8.4 years, 88% HLA-B27+, mean modified Stokes Ankylosing Spondylitis Spinal Score 8.3±16.4. 60% of patients had spinal inflammation by MRI. The stratification based on BASDAI ≥4 disclosed significant differences in most clinical parameters but not for inflammation: patients with nraxSpA and BASDAI <4 versus ≥4 had 0.9±1.4 and 0.5±0.6 inflammatory lesions/patient, respectively (p=0.6), while patients with AS had 3.6±3.7 and 2.7±3.0 inflammatory lesions/patient, respectively (p=0.4).

The burden of inflammation is quite comparable in patients with axSpA—regardless of disease activity. These data clearly challenge the concept of the recommended cut-off point of BASDAI ≥4.

At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000–2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure.

Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02).

Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.

The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR_meta=1.16, 95% CI 1.11 to 1.22; p=4.88x10^–10 and OR_meta=1.67, 95% CI 1.55 to 1.79; p=3.32x10^–46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91x10^–5).

These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.

The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0–3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination.

Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2–3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA >88%, PCA 100% and weighted kappa >0.91).

Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.

A yeast two-hybrid cDNA library was constructed from ST obtained by arthroscopy from patients with RA and screened using the extracellular domains of TLR2 and TLR4 as the bait. Interactions between TLRs and Snapin were demonstrated by reciprocal co-immunoprecipitation. ST was examined by histology, and single- and two-colour immunohistochemistry and quantitative reverse transcriptase PCR. Snapin (SNAP – associated protein) expression in macrophages was examined by Western Blot analysis and confocal microscopy. The ability of Snapin to activate through TLR2 was examined.

Employing a yeast two-hybrid system, Snapin was the most frequently identified molecule that interacted with TLR2. These results were confirmed by pull-down of in vitro-expressed Snapin together with TLR2. By immunohistochemistry and quantitative reverse transcriptase PCR, Snapin was highly expressed in RA ST, and it was readily detected in macrophages, where it co-localised in the late endosomes. ST Snapin expression correlated with inflammation and was not disease specific. Finally, Snapin was capable of activating through TLR2.

These observations identify Snapin as a novel endogenous TLR2 ligand in RA, and thus support a role for persistent TLR2 signalling in the pathogenesis of RA.

mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was analysed by F18-positron emission tomography-scanning and µCT in ttw/ttw mice. Ttw/ttw mice are mice carrying a loss-of-function mutation in NPP1. Calcification of articular cartilage was assessed using von Kossa staining and OA severity using the Mankin score. Cartilage remodelling was investigated by type X collagen immunohistochemistry.

Expression of NPP1, but not the other members of this pathway, inversely correlated with cartilage calcification and OA severity in mouse and humans. Proinflammatory cytokines downregulated the expression of NPP1, demonstrating an influence of inflammation on matrix calcification. Ttw/ttw mutant mice, carrying a loss-of-function mutation in NPP1, exhibit increased bone formation process in joints compared with wild types. Ttw/ttw mice also developed spontaneous OA-like changes, evaluated by histological analysis and in vivo imaging. Ectopic calcifications were associated with increased expression of collagen X in the cartilage.

The authors conclude that OA is characterised by the reactivation of molecular signalling cascades involving proinflammatory cytokines, thereby regulating the pyrophosphate pathway which consequently leads to cartilage ossification, at least in part resembling endochondral ossification.

Data from the Swedish national biologics registry ARTIS were used to analyse characteristics of patients' disease at the start of the first anti-TNF treatment. Means for men and women were compared using t-tests, and non-normally distributed covariates were compared using the Wilcoxon rank-sum test. Linear regression models, adjusted for age and calendar year, were used to investigate the association between sex and each disease activity measurement.

Women were younger and had longer disease duration at treatment start than men. Tender joint count, erythrocyte sedimentation rate, patient's global assessment, patient-reported pain and health assessment questionnaire scores were significantly higher in women, whereas men had a higher level of C-reactive protein (p<0.05 for all comparisons). Swollen joint count and physician's global assessment did not differ by sex.

For women with rheumatoid arthritis, treatment with anti-TNF therapy was initiated at a higher level of subjective disease activity than for men, but at the same level of physician-reported disease activity. These data imply that patients' subjectively experienced disease activity may be discounted in the treatment decision.

Fourteen patients with persistent knee arthritis despite at least two previous injections in an outpatient setting received an intra-articular injection with glucocorticoids, followed by 3 days of admission with bed rest. Clinical efficacy was assessed at 6 and 12 weeks. ST biopsies were performed 2 weeks before and 12 weeks after the injection. The presence of different cell types (T cells, macrophages, fibroblast-like synoviocytes) and numbers of glucocorticoid, androgen and oestrogen α and β receptor positive cells were evaluated by histochemistry.

Patients showed, despite previous failures, good clinical response to glucocorticoid injection, with significant improvement in erythrocyte sedimentation rate, visual analogue scale (VAS) for pain, and joint disability score. The number of steroid hormone receptor positive cells decreased markedly (p<0.05 for all four receptors). The decrease in oestrogen receptor α positive cells correlated significantly with the improvement in VAS for pain and joint disability score. The number of glucocorticoid, androgen and oestrogen α and β receptor positive cells before injection did not predict the effect of treatment.

Intra-articular glucocorticoid injections followed by bed rest for persistent arthritis are clinically effective and significantly decrease the number of steroid hormone receptor positive cells in ST. The relevance of the latter needs further study.

The authors identified all SpA and psoriatic arthritis (PsA) patients in the EAC cohort according to the diagnosis of the treating rheumatologist. A control group consisting of arthritis patients with other diagnoses was matched to the SpA and PsA patients on gender, age and symptom duration. The authors assessed the fulfilment of SpA criteria in all three groups.

Of the patients in the EAC cohort (n=2011), 7.5% was diagnosed with PsA and 3.8% with SpA. In the PsA group, the ClASsification criteria for Psoratic ARthritis (CASPAR) criteria had the highest sensitivity (88.7%). In the SpA group, the Assessment of SpondyloArthritis international Society (ASAS) peripheral SpA and European Spondylarthropathy Study Group (ESSG) criteria had the highest sensitivity (both 48.7%). Specificity of all criteria sets was good: ranging from 88.5% (ESSG) to 100% (Amor).

In early arthritis, sensitivity of SpA classification criteria is modest except for the CASPAR criteria in PsA. However, specificity of classification criteria, including the new ASAS-peripheral SpA criteria, is high.

The authors identified the first available set of consecutive summer and winter visits for every patient from the prospective cohort of PsA. Comparison between summer and winter visits, and comparison of the repeated summer/winter visits, from 1978 until 2011 for the same identified patients was conducted for demographics, disease activity outcomes, laboratory results and treatment. The authors categorised disease activity into high, moderate and low states, and improvement versus flare/worsening. Descriptive statistics were computed and multivariate analyses using logistic regression and generalised estimating equations were conducted.

The first available summer and winter visit were identified for 253 patients, and 1789 observations were analysed. There was no statistically significant difference in patients' demographics, disease activity outcomes, laboratory results and treatment between summer and winter visits. Bath Ankylosing Spondylitis Disease Activity Index scores were greater for summer visits and patients graded their disease as being worse in winter as compared with summer in the univariate analysis, but this difference did not hold in the multivariate analysis.

The change in season does not affect PsA patients' characteristics and disease activity outcomes as determined by the physicians and patients.

Infliximab was down-titrated with 25% of the original dose (3 mg/kg) every 8–12 weeks without interval change until discontinuation or flare in all RA patients with stable low 28-joint disease activity score (DAS28) and stable treatment for >6 months. During 1 year DAS28, RA medication, outpatient clinic visits, RA related absenteeism and EuroQoL5D (European QoL questionnaire, EQ5D) were documented. Prevalence of successful down-titration and changes in DAS28, QoL and costs were described.

In 16% (95% CI 6 to 26) and 45% (95% CI 31 to 59), respectively, infliximab could be discontinued or down-titrated. Mean infliximab dose decreased significantly from 224 mg (95% CI 212 to 236 mg) at start, to 130 mg (95% CI 105 to 154 mg) after 1 year. Median DAS28 increased from 2.5 (p25–75=2.0–2.9) to 2.8 (2.2–3.6) (p=0.002). Extra corticosteroids were given in 8% of the visits. Disease modifying antirheumatic drugs were seldom changed. There was no statistical difference in QoL after down-titration. Mean reduction in the costs was 3474 (95% CI 2457 to 4492) per patient.

In the majority of patients with stable low DAS28 and stable treatment, infliximab can be down-titrated or discontinued, which results in a considerable reduction in costs without influencing QoL.

This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan–Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied.

The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE.

Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.

The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect.

Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA–SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA–SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life.

These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline.

identifiers NCT00424476 and NCT00410384

The authors used 12 commercial ELISAs for ACPA detection in the reference serum and for testing the linearity of the assays by studying twofold serial dilutions. To test the effectiveness of the standardisation, sera from 20 RA patients with variable antibody concentrations were analysed, and the relative concentrations were calculated using both the kit's own curve and the six dilutions of the reference serum as a calibration curve. Fifty sera from normal healthy subjects were used to calculate cut-off values for the reference serum using each commercial kit.

The calibration curve obtained for each of the 12 methods using the reference sample dilutions as calibrator allowed harmonisation of the ACPA concentration of the 20 RA serum samples, significantly reducing the dispersion of the values. The mean coefficient of variation (CV) was reduced from 76.4% to 27.9% (p=0.018) and from 85.9% to 33.5% (p=0.028) for the medium/high and negative samples, respectively. Low positive sera CV was also reduced, but to a smaller degree, from 82.5% to 55.5% (p=0.043).

This first evaluation of the behaviour of the ACPA reference serum demonstrated that it tested positive in all the assays and that it may be used as a reference standard for establishing calibration curves, reducing the dispersion of antibody values and better comparing results obtained from different methods/laboratories.

Data from a previously performed randomised controlled trial were used to investigate the course of pain over 2 years in 222 patients with clinically and radiographically determined hip OA. Pain was measured with a visual analogue scale (0–100). Latent class growth analysis was used to determine the number of trajectories of patients with hip pain due to OA.

Analyses yielded five trajectories of pain due to hip OA. Trajectory 1 (‘mild pain’; n=69) consists of patients with stable mild pain. Patients in trajectory 2 (‘moderate pain’; n=31) fluctuated slightly between moderate and severe pain levels. Trajectory 3 (‘always pain’; n=32) consists of patients with severe pain. Patients in trajectory 4 (‘regularly progressing’; n=48) started with mild pain and progressed slowly to moderate pain. Trajectory 5 (‘highly progressing’; n=42) patients also started with mild pain but quickly progressed to severe pain over 2 years. Compared with the ‘mild pain’ group, patients in the ‘always pain’ group had more severe radiographic hip OA, morning stiffness and decreased range of motion. The ‘highly progressing’ group had more severe radiographic hip OA and morning stiffness.

Latent class growth analysis applied to longitudinal data of patients with hip OA identified five distinct trajectories of pain. More studies are needed to externally validate these findings.

To determine whether AjA can modulate fibrogenesis in murine models of scleroderma.

Bleomycin-induced experimental fibrosis was used to assess the antifibrotic effects of AjA in vivo. In addition, the efficacy of AjA in pre-established fibrosis was analysed in a modified model of bleomycin-induced dermal fibrosis and in mice overexpressing a constitutively active transforming growth factor β (TGFβ) receptor I. Skin fibrosis was evaluated by quantification of skin thickness and hydroxyproline content. As a marker of fibroblast activation, α-smooth muscle actin was examined. To study the direct effect of AjA in collagen neosynthesis, skin fibroblasts from patients with scleroderma were treated with increasing concentrations of AjA. Protein expression of PPAR-, and its endogenous ligand 15d-PGJ2, and TGFβ were assessed before and after AjA treatment.

AjA significantly prevented experimental bleomycin-induced dermal fibrosis and modestly reduced its progression when started 3 weeks into the disease. AjA strongly reduced collagen neosynthesis by scleroderma fibroblasts in vitro, an action which was reversed completely by co-treatment with a selective PPAR- antagonist.

AjA prevents progression of fibrosis in vivo and inhibits fibrogenesis in vitro by stimulating PPAR- signalling. Since therapeutic doses of AjA are well tolerated in humans, it is suggested that AjA as an interesting molecule targeting fibrosis in patients with scleroderma.

Immunohistochemical staining of healthy and OA-affected cartilage was performed for D2. We then assessed allelic balance of DIO2 mRNA within OA-affected cartilage both at and away from the lesion, ligaments and subchondral bone. Allelic balance was measured by the amount of alleles ‘C’ and ‘T’ of the intragenic OA risk polymorphism rs225014 in heterozygous carriers.

A markedly higher amount of D2 positive cells and staining intensity was observed in OA cartilage. A significant, 1.3-fold higher presence was observed for the OA-associated rs225014 ‘C’ allele relative to the ‘T’ allele of DIO2, which was significant in 28 of 31 donors.

In OA cartilage, D2 protein presence is increased. The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele ‘C’ of rs225014 more abundant than the wild-type ‘T’ allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.

The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β₂ glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.

The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).

Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.

Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported.

459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70–73% and 75–81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively.

In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ~57–67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring.

164 patients with axial SpA (88 with AS and 76 with non-radiographic axial SpA) were selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and the data on NSAIDs intake. Spinal radiographs were scored by two trained readers in a concealed randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system. An index of the NSAID intake counting both dose and duration of drug intake was calculated.

High NSAIDs intake (NSAID index≥50) in AS was associated with lower likelihood of significant radiographic progression defined as an mSASSS worsening by ≥2 units: OR=0.15, 95% CI 0.02 to 0.96, p=0.045 (adjusted for baseline structural damage, elevated C reactive protein (CRP) and smoking status) in comparison with patients with low NSAIDs intake (NSAID index<50). This effect was most pronounced in patients with baseline syndesmophytes plus elevated CRP: mean mSASSS progression was 4.36±4.53 in patients with low NSAIDs intake versus 0.14±1.80 with high intake, p=0.02. In non-radiographic axial SpA, no significant differences regarding radiographic progression between patients with high and low NSAIDs intake were found.

A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS. In non-radiographic axial SpA this effect is less evident, probably due to a low grade of new bone formation in the spine at this stage.

The authors aimed to define minor, moderate and major response criteria for the SDAI.

The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD).

Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses.

These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.

BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up.

VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up.

Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.

The authors performed logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend Index.

Deprivation predicted RF but not ACPA positivity, independent of smoking. The ORs for trend across tertiles, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were 1.14 (95% CI 1.01 to 1.29) for RF and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles (HLA-DRB1 shared epitope and PTPN22 rs2476601) that have previously been shown to modify the effect of smoking on ACPA and RF positivity.

Among patients with RA, deprivation predicted RF positivity but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. Deprivation may be a marker for previously unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery.

1418 patients with 4885 x-ray sets of both hands and feet of four independent data sets were studied. First, explorative analyses were performed on 600 patients with early RA enrolled in the Leiden Early Arthritis Clinic. Twenty-five single-nucleotide polymorphisms (SNPs) tagging IL-15 were tested. Second, SNPs with significant associations in the explorative phase were genotyped in data sets from Groningen, Sheffield and Lund. In each data set, the relative increase of the progression rate per year in the presence of a genotype was assessed. Subsequently, data were summarised in an inverse weighting meta-analysis.

Five SNPs were significantly associated with rate of joint destruction in phase 1 and typed in the other data sets. Patients homozygous for rs7667746, rs7665842, rs2322182, rs6821171 and rs4371699 had respectively 0.94-, 1.04-, 1.09-, 1.09- and 1.09-fold rate of joint destruction compared to other patients (p=4.0x10^–6, p=3.8x10^–4, p=5.0x10^–3, p=5.0x10^–3 and p=9.4x10^–3).

Independent replication was not obtained, possibly due to insufficient power. Meta-analyses of all data sets combined resulted in significant results for four SNPs (rs7667746, p<0.001; rs7665842, p<0.001; rs4371699, p=0.01; rs6821171, p=0.01). These SNPs were also significant after correction for multiple testing.

Genetic variants in IL-15 are associated with progression of joint destruction in RA.

A qualitative study involving semistructured face-to-face interviews with patients and health professionals from 25 Nottinghamshire general practices and one central National Health Service hospital.

Twenty gout sufferers and 18 health professionals (six general practitioners, five hospital physicians, seven practice nurses).

A number of key themes emerged suggesting that several factors impact on patients' access to recommended treatments. The main barriers were patient experiences and lay beliefs of their condition which affected seeking advice and adherence to treatment. There was universal lack of knowledge and understanding of the causes and consequences of gout and that it can be treated effectively by lifestyle change and use of urate lowering therapy (ULT). All participants associated gout with negative stereotypical images portrayed in Victorian cartoons. Many viewed it as self-inflicted or part of ageing and only focused on managing acute attacks rather than treating the underlying cause. The main provider barriers that emerged related to health professionals' lack of knowledge of gout and management guidelines, reflected in the suboptimal information they gave patients and their reluctance to offer ULT as a ‘curative’ long-term management strategy.

There are widespread misconceptions and lack of knowledge among both patients and health professionals concerning the nature of gout and its recommended management, which leads to suboptimal care of the most common inflammatory joint disease and the only one for which we have ‘curative’ treatment.

Serum levels of adiponectin, leptin, resistin, visfatin, vaspin and lipids were determined in a well-defined cohort of patients with RA before and after 16 weeks of adalimumab treatment (adalimumab cohort). The same parameters were analysed in two other cohorts of patients with RA before and after 2 weeks of high-dose prednisolone (high GC cohort) and before and after 22 weeks of treatment with a combination regimen with tapered high-dose prednisolone (COBRA -GC cohort). Radiographs of hands and feet (adalimumab and COBRA-GC cohorts) were assessed at baseline and after treatment.

Treatment with adalimumab or GC showed opposing effects on vaspin and visfatin levels. Lipid levels improved after several months of adalimumab or GC treatment; in the adalimumab cohort, this was related to reduced visfatin levels, independent of C reactive protein levels. After long-term adalimumab or GC treatment, resistin levels declined, which was associated with a decrease in inflammation markers. In the adalimumab cohort, baseline resistin levels were predictive of baseline radiological damage, independent of anticitrullinated peptide antibodies status or C reactive protein levels.

Changes in serum adipocytokine levels were treatment specific, further strengthening the role of visfatin and resistin in several disease manifestations of RA.

The authors examined 1443 Caucasian SSc patients enrolled in the Genetics versus Environment In Scleroderma Outcome Study (GENISOS) and Scleroderma Family Registry (n = 914 – discovery cohort) and The Johns Hopkins Scleroderma Cohort (n = 529 – replication cohort). Forced vital capacity (FVC)% predicted was used as a surrogate for ILD severity. Five single nucleotide polymorphisms, IRF5 (rs10488631, rs12537284, rs4728142), STAT4 (rs3821236), CD247 (rs2056626) reached genome-wide significance in the SSc-GWAS and were examined in the current study.

Overall, 15.5% of the patients had died over the follow-up period of 5.5 years. The IRF5 rs4728142 minor allele was predictive of longer survival in the discovery cohort (p = 0.021) and in the independent replication cohort (p = 0.047) and combined group (HR: 0.75, 95% CI 0.62 to 0.90, p = 0.002). The association of this SNP with survival was independent of age at disease onset, disease type and autoantibody profile (anticentromere and antitopoisomerase antibodies). The minor allele frequency of IRF5 rs4728142 was 49.4%.

Moreover, IRF5 rs4728142 minor allele correlated with higher FVC% predicted at enrolment (p = 0.019). Finally, the IRF5 rs4728142 minor allele was associated with lower IRF5 transcript expression in patients and controls (p = 0.016 and p = 0.034, respectively), suggesting that the IRF5, rs4728142 SNP, may be functionally relevant.

An SNP in the IRF5 promoter region (rs4728142), associated with lower IRF5 transcript levels, was predictive of longer survival and milder ILD in patients with SSc.

At week 48, patients who reached study remission (Assessment of Spondyloarthritis international Society (ASAS) plus MRI remission) were followed up without active treatment up to 1 year. In case of a flare, patients were treated with ETA for another year. All patients who were not in ASAS plus MRI remission at week 48 were treated with ETA in year 2.

ASAS plus MRI remission at week 48 was reached significantly more often in ETA-treated compared to SSZ-treated patients (33% vs 11%, p=0.03). However, the flare rate was not different between these two groups: 69% in the ETA group versus 75% in the SSZ group. Only 8% of patients initially treated with ETA versus 3% of those initially treated with SSZ reached permanent drug-free remission (not significant). After treatment with ETA over 1 year, patients with flare showed an improvement in all clinical and imaging variables.

Patients with axial spondyloarthritis treated with ETA over 1 year did not reach drug-free remission in a higher percentage compared to patients from a control group treated with SSZ.

68 consecutive newly diagnosed pSLE patients prospectively followed in our lupus cohort with three annual dual energy x-ray absorptiometry (DEXA) examinations were studied. Low LS BMD was defined as z-score ≤–2.0. Baseline and longitudinal clinical features including disease activity, treatment and bone physiology markers were collected. Hierarchical linear modelling was used to model trajectory of LS BMD and identify predictors.

Women constituted 84% of the cohort and median age at diagnosis was 13.1 years. The mean LS BMD z-scores decreased over time (–0.42 at first, –1.02 at second and –1.11 at third DEXA). Initially 9% of patients had a low BMD, which increased to 19% by 3 years after diagnosis. 35% of patients deteriorated in BMD category from the first to third DEXA. LS BMD (adjusted by height-for-age z-score) followed a general deteriorating trajectory of –0.06 z-score/year from diagnosis. Increased rate of deterioration of BMD trajectory was predicted by pubertal status at diagnosis, increased interval cumulative steroid exposure and decreased weight z-scores.

The LS BMD of pSLE patients followed a general deteriorating trend over time and could be predicted by a combination of pubertal status at diagnosis, interval cumulative doses of steroids and weight z-scores. Interval cumulative steroid dose represents an important target that clinicians may modify to ameliorate deteriorating BMD trajectory over time.

The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic.

Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)).

Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.

To compare the effectiveness of RTX against anti-TNF agents in preventing joint damage in patients with RA who have experienced inadequate response to at least one prior anti-TNF agent.

This is a prospective cohort study within the Swiss registry of patients with RA who discontinued at least one anti-TNF agent and subsequently received either RTX or an alternative anti-TNF agent. The primary outcome, progression of radiographic joint erosions (Ratingen erosion score)over time, and the secondary outcome, functional disability (Health Assessment Questionnaire Disability Index), were analysed using regression models for longitudinal data and adjusted for potential confounders.

Of the 371 patients included, 104 received RTX and 267 received an alternative anti-TNF agent. During the 2.6-year median follow-up period, the rates of Ratingen erosion score progression were similar between patients taking RTX and patients taking an alternative anti-TNF agent (p=0.67). The evolution of the Health Assessment Questionnaire score was statistically significantly better in the RTX group (p=0.016), but the magnitude of the effect was probably not clinically relevant.

This observational study suggests that RTX is as effective as an alternative anti-TNF agent in preventing erosions in patients with RA who have previously experienced inadequate response to anti-TNF agents.

A case–control study was nested within a Finnish cohort of 36 000 adults who had neither arthritis nor a history of arthritis at baseline examination in 1966–1972. Among them, 151 subjects developed seropositive (ie, positive for rheumatoid factor) RA, and 67 subjects developed seronegative RA by late 1989. One or two control subjects were chosen for every case. Preillness serum specimens were analysed for antibodies against synthetic TELO-I, TELO-II, MCV and CCP.

The mean levels of anti-TELO-I, anti-TELO-II, anti-CCP and anti-MCV antibodies were higher in subjects who later developed seropositive or seronegative RA than in controls. In subjects who later developed seronegative RA, anti-TELO-I and anti-TELO-II antibodies were statistically significantly higher compared with controls (p=0.005 and p=0.013). In the highest tertiles of anti-MCVs and anti-TELO-I levels, the OR for rheumatoid-factor-positive RA were 2.66 (95% CI 1.48 to 4.77) or 2.51 (CI 1.48 - 4.28), respectively. The subjects ranked into the highest tertiles of both anti-TELO-I and anti-MCV antibodies had a 4.56 OR (95% CI 1.82 to 11.46) of developing seropositive RA compared with those in the lowest tertiles of these antibodies. For the co-occurrence for high anti-TELO-II and anti-MCV antibodies, the corresponding OR was 3.62 (95% CI 1.37 to 9.54).

Antibodies to TELO-I or TELO-II and MCV exert a synergistic effect on the risk of developing seropositive RA.

EQ-5D and SF-6D utility measures were assessed in 813 patients with EA over 2 years. Responsiveness was analysed by the standardised response mean (SRM) and effect size between baseline and 6, 12 and 24 months for the entire sample and subgroups by disease evolution (increase or decrease in Disease Activity Score for 28 joints). Bootstrap methods were used to estimate 95% CI.

The EQ-5D provided larger absolute mean change estimates with greater variance than the SF-6D, whatever the direction of change. At 12 months, the SF-6D was more sensitive to change with improved condition than the EQ-5D: SRM 0.83 (0.82 to 0.84) versus 0.57 (0.56 to 0.58). In contrast, the EQ-5D was more sensitive to change with deteriorated condition than the SF-6D: SRM –0.20 (–0.23 to –0.18) versus –0.11 (–0.14 to –0.08). Results were similar for 6 and 24 months.

The SF-6D was more responsive than the EQ-5D with improved EA condition. Confidence in the relative cost-effectiveness of two treatments would be better with the SF-6D because of its smaller variance. The SF-6D provided more conservative cost-effectiveness ratios than the EQ-5D and may be more appropriate for trials of biological treatments for patients with EA.

Data from the Netherlands Information Network of General Practice, a representative Dutch sample of 360 000 registered patients, were used. Prevalence rates of hypothyroidism were calculated, and multilevel logistic regression analyses were used to calculate CVD prevalence rates.

Hypothyroidism prevalence was 6.5% in female patients with arthritis compared to 3.9% in controls (p<0.001). CVD prevalence was 4.3% in patients with hypothyroidism, 5.9% in patients with inflammatory arthritis, 14.3% in patients with hypothyroid inflammatory arthritis and 2.1% in controls. Adjusted CVD prevalence rates were 1.2 (95% CI 0.99 to 1.4) for hypothyroidism, 1.5 (95% CI 1.1 to 2.0) for inflammatory arthritis and 3.7 (95% CI 1.7 to 8.0) for hypothyroid inflammatory arthritis as compared with controls.

These data raise awareness on the coexistence of hypothyroidism and inflammatory arthritis and emphasise the importance of cardiovascular risk management in these patients, particularly when hypothyroidism and inflammatory arthritis coexist.

Sixty-six consecutive patients with SSc according to the LeRoy and Medsger criteria underwent NVC assessment at baseline. Videocapillaroscopic images were classified into ‘normal’, ‘early’, ‘active’ or ‘late’ NVC pattern. Clinical evaluation was performed for nine organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart and kidney) according to the disease severity scale of Medsger (DSS) at 18–24 months of follow-up. Severe clinical involvement was defined as category 2–4 per organ of the DSS.

NVC patterns were significantly associated with future severe, peripheral vascular/lung involvement at 18–24 months. The OR rose steadily throughout the patterns. The OR for future severe peripheral disease based on simple/multiple (correcting for disease duration, subset and medication) logistic regression was 2.49/2.52 (95% CI 1.33 to 5.43, p=0.003/1.11 to 7.07, p=0.026) for early, 6.18/6.37 for active and 15.35/16.07 for late NVC scleroderma patterns versus the normal NVC pattern. The OR for future severe lung involvement based on simple/multiple regression was 2.54/2.33 (95% CI 1.40 to 5.22, p=0.001/1.13 to 5.52, p=0.021) for early, 6.43/5.44 for active and 16.30/12.68 for late NVC patterns.

This pilot study is the first demonstrating an association between baseline NVC patterns and future severe, peripheral vascular and lung involvement with stronger odds according to worsening scleroderma patterns. This may indicate a putative role of capillaroscopy as a biomarker.

610 recent onset RA or UA patients started with MTX 25 mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks. Percentage remissions after 4 months were compared between RA (1987 or 2010 criteria) and UA. Predictors for remission were identified.

With the 2010 criteria, 19% more patients were classified as RA than with the 1987 criteria, but similar remission rates were achieved: 291/479 (61%) 2010 classified RA and 211/264 (58%) 1987 classified RA patients (p=0.52), and 79/122 (65%) UA patients (p=0.46). Anticitrullinated protein antibodies (ACPA) positive RA patients achieved more remission (66%) than ACPA negative RA patients (51%, p=0.001), but also had a lower mean baseline Disease Activity Score (DAS) (3.2 vs 3.6, p<0.001). Independent predictors for remission were male sex, low joint counts, DAS and Health Assessment Questionnaire, low body mass index and ACPA positivity.

Initial treatment with MTX and a tapered high dose of prednisone results in similarly high remission percentages after 4 months (about 60%) in RA patients, regardless of fulfilling the 1987 or 2010 criteria, and in UA patients. Independent predictors indicate that initiating treatment while disease activity is relatively low results in more remission.

The authors identified all patients with first-time MI in the Danish National Patient Register from 2002 to 2009 and gathered individual level information including pharmacy records from nationwide registers. Initiation of standard care post-MI secondary prevention drugs, that is, aspirin, β-blockers, clopidogrel, renin angiotensin system (RAS) blockers and statins, was determined after discharge. In addition, adherence to each drug was evaluated as the proportion of patients on treatment during follow-up and time to first treatment gap.

A total of 66 107 MI patients (37% women) were discharged alive; 877 were identified as RA patients (59% women). Thirty days after discharge, RA was associated with significantly lower initiation of aspirin (OR 0.80 (0.67–0.96)), β-blockers (0.77 (0.65–0.92)) and statins (0.69 (0.58–0.82)), while initiation of RAS blockers (0.80 (0.57–1.11)) and clopidogrel (0.88 (0.75–1.02)) was non-significantly reduced. These estimates were virtually unchanged at day 180 and the results were corroborated by Cox regression analyses. Adherence to statins was lower in RA patients relative to non-RA patients (HR for treatment gap of 90 days: 1.26 (1.07–1.48)), while no significant differences were found in adherence to the other drugs.

In this nationwide study of unselected patients with first-time MI, a reduced initiation of secondary prevention pharmacotherapy was observed in RA patients. This undertreatment may contribute to the increased cardiovascular disease burden in RA and the underlying mechanisms warrant further study.

A single nucleotide polymorphism of STAT4, rs7574865, was genotyped using TaqMan assay in 1143 Japanese individuals. The first set comprised 138 polymyositis/dermatomyositis patients and 289 controls and the second set comprised 322 patients and 394 controls. 460 patients (273 polymyositis and 187 dermatomyositis patients) and 683 controls were genotyped.

rs7574865T conferred a risk of polymyositis/dermatomyositis with an OR of 1.37 (95% CI 1.16 to 1.64; p=4x10^–4; p_corr=0.0012). Both polymyositis and dermatomyositis exhibited high associations with the rs7574865T allele (polymyositis: OR=1.36, 95% CI 1.11 to 1.67; p=0.0039; p_corr=0.012; dermatomyositis: OR=1.40, 95% CI 1.10 to 1.78; p=0.0054; p_corr=0.016). The association between this STAT4 polymorphism and interstitial lung disease (ILD) was also investigated in the first set of polymyositis/dermatomyositis patients (n=138); those with ILD (n=79) bore rs7574865T more frequently compared with controls (OR 1.59, 95% CI 1.10 to 2.28; p=0.013; p_corr=0.039).

This is the first study to show a positive association between a STAT4 polymorphism and polymyositis/dermatomyositis, suggesting that polymyositis/dermatomyositis shares a gene commonly associated with the risk of other autoimmune diseases.

Forty crystal-proven gout patients (17 tophaceous) and 40 controls with other arthritic conditions prospectively underwent DECT scans of all peripheral joints using a gout protocol that color-codes the composition of tissues. A blinded radiologist identified urate deposition to calculate specificity and sensitivity of DECT for gout. Inter-rater volumetric reproducibility was determined by two independent radiologists on 40 index tophi from the 17 tophaceous gout patients using automated software.

The mean age of the 40 gout patients was 62 years, the mean gout duration was 13 years and 87% had a history of urate-lowering therapy (ULT). The specificity and sensitivity of DECT for gout were 0.93 (95% CI, 0.80 to 0.98) and 0.78 (0.62 to 0.89), respectively. When the authors excluded three gout cases with unreadable or incomplete scans, the sensitivity was 0.84 (95% CI, 0.68 to 0.94). The urate volumes of 40 index tophi ranged from 0.06 cm³ to 18.74 cm³ with a mean of 2.45 cm³. Interobserver and intraobserver intraclass correlation coefficients for DECT volume measurements were 1.00 (95% CI, 1.00 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) with corresponding bias estimates (SD) of 0.01 (0.00) cm³ and 0.01 (0.03) cm³.

These prospective data indicate high reproducibility of DECT urate volume measures. The specificity was high, but sensitivity was more moderate, potentially due to frequent ULT use in our patients.

The authors conducted a double-blind randomised crossover trial of a multi-modal realignment treatment for medial tibiofemoral OA. Trial participants met American College of Rheumatology criteria for OA, with knee pain, aching or stiffness on most days of the past month and radiographic evidence of a definite osteophyte with predominant medial tibiofemoral OA. The authors tested two different treatments: (A) control treatment consisting of a neutral knee brace (no valgus angulation), flat unsupportive foot orthoses and shoes with a flexible mid-sole; and (B) active treatment consisting of a valgus knee brace, customised neutral foot orthoses and shoes designed for motion control. For each subject, the trial lasted 30 weeks, including 12 weeks each of active treatment and control treatment separated by a 6-week washout period. The primary outcome of the linear regression model was change in knee pain and function, as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

80 participants with medial tibiofemoral OA were randomised. Their mean age was 62 years, their mean body mass index was 34 kg/m² and their mean WOMAC Pain score was 9.2 (0–20 scale). There was no evidence of a carryover effect. The regression model demonstrated that the mean difference in pain between the active treatment and the control treatment was –1.82 units (95% CI –3.05 to –0.60; p=0.004) on the WOMAC Pain scale, indicating a small but statistically significant decrease in pain with the multi-modal active treatment. For WOMAC Function, the realignment intervention had a non-significant effect on function, with a –2.90 unit decrease (95% CI –6.60 to 0.79) compared with the control condition (p=0.12).

Multi-modal realignment treatment decreases pain in persons with medial tibiofemoral OA.

Adults aged 50–80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale.

At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm². VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (–14.5 mm, 95% CI –28.1 to –0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (–175.7 mm², 95% CI –327.2 to –24.3) with a trend after 12 months (–146.5 mm², 95% CI –307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms.

ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach.

ACTRN 12609000399291.

Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification.

Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA.

Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.

To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate.

Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28).

Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p<0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p<0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score <2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity.

In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.

56 single nucleotide polymorphisms (SNPs) mapping to 41 genes previously reported as RA susceptibility loci were selected for investigation. PsA was defined as an inflammatory arthritis associated with psoriasis and subjects were recruited from the UK and Ireland. Genotyping was performed using the Sequenom MassArray platform and frequencies compared with data derived from large UK control collections.

Significant evidence for association with susceptibility to PsA was found toa SNP mapping to the REL (rs13017599, p_trend=5.2x10⁴) gene, while nominal evidence for association (p_trend<0.05) was found to seven other loci including PLCL2 (rs4535211, p=1.7x10^–3); STAT4 (rs10181656, p=3.0x10^–3) and the AFF3, CD28, CCL21, IL2 and KIF5A loci. Interestingly, three SNPs demonstrated opposite effects to those reported for RA.

The REL gene, a key modulator of the NFB pathway, is associated with PsA but the allele conferring risk to RA is protective in PsA suggesting that there are fundamental differences in the aetiological mechanisms underlying these two types of inflammatory arthritis.

PHAROS is a multicentre prospective longitudinal cohort of patients with SSc "at risk" or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups.

206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (≥30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS).

Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP ≥30 mm Hg.

In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mgx2+MTX (OCR 200; n=200) or OCR 500 mgx2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (mTSS) at week 104). Analyses are reported for week 52 outcomes.

At week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in mTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)).

OCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections.

Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.

Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.

A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.

Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800–1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500–730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0–100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates

The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>–9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated.

Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety.

RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy.

26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission.

The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.

The frequency of the enhancer HS1.2 alleles was determined in two cohorts of patients with SLE (n=293) and in 1185 controls. Electrophoretic mobility shift assays (EMSA) were carried out with B cell nuclear extracts with different probes of HS1.2 alleles *1 and *2 to map the consensus binding sites of the nuclear factors. A confirmatory cohort of 121 patients with SLE was also included.

The frequency of allele *2 of the HS1.2 enhancer was significantly increased in patients with SLE compared with controls (OR 1.60, 95% CI 1.33 to 1.92, p<0.001). EMSA experiments showed the presence of the Sp1 binding site in both alleles whereas only allele *2 carried the consensus for the NF-B factor. The presence versus absence of allele *2 in patients with SLE correlated with a higher concentration of IgM levels and with the expression of B cell activating factor receptor (BAFF-R).

The increased frequency of allele *2 in patients with SLE identifies a new genetic risk factor for SLE. A possible biological effect of the polymorphism could be the difference observed in the localisation of an NF-B binding site which is specific for allele *2 and absent in allele *1. These observations suggest a functional effect of the HS1.2 enhancer in this disease.

To compare the efficacy and safety of biological agents after TNFi-IR.

A systematic literature search was carried out using Medline and Cochrane databases, as well as http://www.clinicaltrials.gov, and bibliographies of the retrieved literature were searched by hand. Randomised, placebo-controlled trials that enrolled patients with RA with TNFi-IR were included and American College of Rheumatology (ACR) response as primary efficacy outcome and adverse events (AEs), serious adverse events (SAEs) and serious infections (SIs) as safety measures were extracted. An indirect meta-analysis with pairwise comparisons of efficacy and safety data was then carried out using ORs or risk differences (RDs) in a random effects model.

In four randomised controlled trials with 24 weeks' follow-up, direct comparisons of abatacept, golimumab, rituximab and tocilizumab versus placebo showed statistically significant mean ORs of 3.3–8.9 for ACR20, 5.5–10.2 for ACR50 and 4.1–13.5 for ACR70. Risks of AEs, SAEs and SIs versus placebo were non-significant. Indirect pairwise comparisons of the four biological agents showed no significant differences in ACR50 and ACR70. Golimumab had a significantly lower OR (0.56–0.59) for ACR20 but significantly fewer AEs (RD 0.13–0.18). Efficacy after one versus multiple TNFi failures did not differ significantly between the different biological agents.

In patients refractory to one or more TNFi, new biological agents provide significant improvement with good safety. Lacking head-to-head trials, indirect meta-analysis enables a comparison of effectiveness and safety of biological agents with each other and shows that all biological agents have similar effects.

RA patients enrolled in the CORRONA registry newly prescribed adalimumab (n=874), etanercept (n=640), or infliximab (n=728) were stratified based on previous anti-TNF use. Clinical effectiveness at 6, 12 and 24 months was examined using the modified American College of Rheumatology response criteria (mACR20/50/70) and achievement of remission (28-joint disease activity score (DAS28) and clinical disease activity index (CDAI)) in unadjusted and adjusted analyses. The persistence of anti-TNF treatment was examined using Cox proportional hazard models.

Among 2242 patients (1475 biologically naive, 767 switchers), mACR20, 50 and 70 responses were similar (p>0.05) for adalimumab, etanercept and infliximab at all time points, as were rates of CDAI and DAS28 remission (p>0.05). Response and remission outcomes were consistently inferior for switched versus biologically naive patients. The adjusted OR for achieving an mACR20 response was 0.54 (95% CI 0.38 to 0.76) in first-time switchers and 0.42 (95% CI 0.23 to 0.78) in second-time switchers versus biologically naive patients at 6 months. The adjusted OR for achieving DAS28 remission were 0.29 (95% CI 0.15 to 0.58) for first-time switchers and 0.26 (95% CI 0.08 to 0.84) for second-time switchers. Persistence was higher in biologically naive patients, for whom persistence was highest with infliximab.

No differences in rates of drug response or remission were observed among the three anti-TNF. Infliximab was associated with greater persistence in biologically naive patients. Response, remission and persistence outcomes were diminished for patients who switched anti-TNF.

To assess prospectively the prevalence, characteristics and topography of LVV in patients with newly diagnosed GCA and to determine the associated clinical and laboratory features.

CT angiography (CTA) was performed in 40 consecutive patients with newly diagnosed biopsy-proven GCA. Patients were treatment-naïve or had been treated with corticosteroids for <3 days. Vessel wall thickness and vessel diameter (dilation or stenoses) at four aortic segments (ascending aorta, aortic arch, descending thoracic and abdominal aorta) and at the main aortic branches were evaluated.

LVV was detected in 27 patients (67.5%). The vessels involved were as follows: aorta (26 patients, 65%), brachiocephalic trunk (19 patients, 47.5%), carotid arteries (14 patients, 35%), subclavian arteries (17 patients, 42.5%), axillary arteries (7 patients, 17.5%), splanchnic arteries (9 patients, 22.5%), renal arteries (3 patients, 7.5%), iliac arteries (6 patients, 15%) and femoral arteries (11 patients, 30%). Dilation of the thoracic aorta was already present in 6 patients (15%). Cranial ischaemic events were significantly less frequent in patients with LVV (p=0.029). Treatment-naïve patients had a higher frequency of LVV (77% vs 29%, p=0.005).

CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

Association between α-fibrinogen (FGA), β-fibrinogen (FGB) and F13A genotypes with CRP levels was tested in two cohorts with longitudinal CRP measurements. Discovery and replication cohorts consisted of 288 RA (913 observations) and 636 non-RA patients (2541 observations), respectively.

Genotype FGB –455G>A (rs1800790) was associated with CRP elevations (≥10 mg/l) in both cohorts (RA, OR per allele 0.69, p=0.0007/P_adj<0.015; non-RA, OR 0.70, p=0.0004/p_adj<0.02; combined, OR 0.69, p<10^–5/p_adj=0.001). Genotype F13A 34VV (rs5985) was conditional for the association of FGB –455G>A with CRP as indicated by a clear restriction on F13A 34VV individuals and a highly significant heterogeneity between F13A 34VV and F13A 34L genotypes (p<10^–5, p_adj=0.001). In both cohorts, mean CRP levels significantly declined with ascending numbers of FGB –455A alleles. Genotype FGA T312A (rs6050) exhibited opposite effects on CRP compared with FGB –455G>A. Again, this relation was dependent on F13A V34L genotype.

Novel genetic determinants of CRP completely unrelated to previously known CRP regulators were identified. Presumably, these haemostatic gene variants modulate inflammation by influencing fibrin crosslinking. These findings could give new perspectives on the genetic background of inflammation control.

HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL's antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay.

Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2%±11.1%) and controls (39.5%±8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=–0.39, p=0.01) and erythrocyte sedimentation rate, (r=–0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL's ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=–0.34, p=0.03).

The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL's antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.

Thirty-nine patients with PMR (age 72±8 years, 44% men, blood pressure (BP) 134/75±16/9 mm Hg) and 39 age-, sex- and BP-matched control subjects underwent aortic pulse wave velocity (PWV) determination. Aortic augmentation as a measure of the impact of the reflection wave on central haemodynamics was also measured and corrected for heart rate. Twenty-nine of the patients were re-examined after 4 weeks of treatment with prednisone at a dose of 15 mg/day.

Aortic PWV was higher in patients with PMR than in control subjects (12.4±4 vs 10.2±2 m/s, p<0.01). Treatment was followed by a reduction in heart rate (from 78±12 to 70±10 beats/min, p<0.001) and no significant change in BP. Aortic PWV decreased after prednisone treatment (from 11.8±3 to 10.5±3 m/s, p=0.015), and the difference was independent of BP and heart rate changes. The change in aortic PWV had a direct correlation with percentage change in plasma C reactive protein (r=0.40, p=0.037). Treatment was also associated with a significant reduction in aortic augmentation index (from 34±7% to 29±8%, p=0.012).

Polymyalgia rheumatica is associated with increased aortic stiffness which may improve upon reduction of systemic inflammation induced by treatment with glucocorticoids.

Twenty-eight patients with pSS treated with rituximab (1000 mg) infusions on days 1 and 15 were included in the study. Data were collected prospectively at baseline and 16, 24, 36, 48 and 60 weeks after treatment. Internal responsiveness was assessed using standardised response means (SRM) and effect sizes (ES). SRM and ES <0.5, 0.5–0.8 and >0.8 were interpreted as small, moderate and large, respectively. External responsiveness was assessed using Spearman correlation coefficients.

Median (range) ESSPRI and ESSDAI scores at baseline were 6.7 (0.3–9.0) and 8 (2–18), respectively. Both indices improved significantly after treatment. SRM and ES values for ESSPRI and ESSDAI were ≥0.8 at week 16 and decreased afterwards, and were larger for ESSDAI than for ESSPRI. SRM and ES values for patient's and physician's global disease activity (GDA) and rheumatoid factor broadly followed the pattern of those of ESSPRI and ESSDAI. SRM and ES for stimulated whole salivary flow were small at all time points. At baseline and for most change scores, moderate to good correlations were found between ESSPRI and patient's GDA and between ESSDAI and physician's GDA. Poor association was found between ESSPRI and ESSDAI.

ESSPRI and ESSDAI are sensitive measures of change in disease activity after therapeutic intervention, which supports the usefulness of these indices for future clinical trials in patients with pSS. The responsiveness of ESSDAI was greater than that of ESSPRI.

The CRP and ESR values and the corresponding JADAS scores (JADAS10/27/71) were compared in a longitudinal cohort study of 389 children newly diagnosed with juvenile idiopathic arthritis (JIA) in the Nordic JIA study. The construct validity and the discriminative and predictive ability of JADAS were assessed during a median disease course of 8 years by comparing JADAS with other measures of disease activity and outcome.

At the first study visit the correlation between JADAS27-CRP and JADAS27-ESR was r=0.99 whereas the correlation between CRP and ESR was r=0.57. Children with higher JADAS scores had an increased risk of concomitant pain, physical disability and use of disease-modifying antirheumatic drugs (DMARDs). A higher JADAS score at the first study visit also significantly predicted physical disability, damage and no remission off medication at the final study visit, and also use of DMARDs during the disease course. Sensitivity to change, demonstrated as change in JADAS score compared with the American College of Rheumatology paediatric measures of improvement criteria, mostly showed excellent classification ability.

The JADAS-CRP and JADAS-ESR correlate closely, show similar test characteristics and are feasible and valid tools for assessing disease activity in JIA.

In 15 tertiary care hospitals, consecutive patients with rheumatoid arthritis, spondylarthropathies or Crohn's disease were screened for LTBI before anti-TNF therapy with TST, QuantiFERON TB Gold in tube (QTF-Gold IT) and T-SPOT.TB at the same time. The potential diagnosis of LTBI and the effect on the decision to begin antibiotic prophylaxis were assessed.

Among 429 patients, 392 had results for the three tests. The results for TST, T-SPOT.TB and QTF Gold IT were positive for 35.2%, 15.1% and 9.9% of patients, respectively (p<0.0001). Antibiotics were required for 177 patients (45.2%) if positive TST results were included in the LTBI definition, 107 patients (27.3%) if TST results were replaced with results from one of the IGRA tests and 84 patients (21.4%) if TST results were replaced with QTF-Gold IT results (p<0.0001). The decision on the use of antibiotic prophylaxis was changed for 113 patients (28.8%, 95% CI 24.4% to 33.6%) if TST results were replaced with QTF-Gold IT results.

Replacing TST with IGRA for determining LTBI allowed the proportion of patients with immune-mediated inflammatory diseases needing prophylactic anti-TB antibiotics before beginning anti-TNF agents to be reduced by half.

TrialRegNo: NCT00811343.

Data from randomised, controlled trials of etanercept in patients with RA, PsA and psoriasis were analysed. HRQoL was assessed by the medical outcomes survey short form 36 (SF-36) physical (PCS) and mental (MCS) component summary and domain scores. Baseline comparisons with age and gender-matched norms and treatment-associated changes in domain scores were quantified using spydergrams and the health utility SF-6D measure.

Mean baseline PCS scores were lower than age and gender-matched norms in patients with RA and PsA, but near normative values in patients with psoriasis; MCS scores at baseline were near normal in PsA and psoriasis but low in RA. Treatment with etanercept resulted in improvements in PCS and MCS scores as well as individual SF-36 domains across all indications. Mean baseline SF-6D scores were higher in psoriasis than in RA or PsA; clinically meaningful improvements in SF-6D were observed in all three patient populations following treatment with etanercept.

Patients with RA, PsA and psoriasis demonstrated unique HRQoL profiles at baseline. Treatment with etanercept was associated with improvements in PCS and MCS scores as well as individual domain scores in patients with RA, PsA and psoriasis.

A case-control analysis matched 1947 serious infection cases to five controls, selected from 16207 RA patients aged ≥65 between 1985–2003 in Quebec, Canada. Adjusted odds ratios for infection associated with different GC patterns were estimated using conventional models and a weighted cumulative dose (WCD) model.

The WCD model predicted risks better than conventional models. Current and recent GC doses had highest impact on current risk. Doses taken up to 2.5 years ago were also associated with increased risk, albeit to a lesser extent. A current user of 5mg prednisolone had a 30%, 46% or 100% increased risk of serious infection when used continuously for the last 3 months, 6 months or 3 years, respectively, compared to a non-user. The risk associated with 5mg prednisolone taken for the last 3 years was similar to that associated with 30mg taken for the last month. Discontinuing a two-year course of 10mg prednisolone six months ago halved the risk compared to ongoing use.

GC therapy is associated with infection risk in older patients with RA. The WCD model provided more accurate risk estimates than conventional models. Current and recent doses have greatest impact on infection risk, but the cumulative impact of doses taken in the last 2–3 years still affects risk. Knowing how risk depends on pattern of GC use will contribute to an improved benefit/harm assessment.

To develop a self-administered tool integrating the perspectives of the patient and the rheumatologist, enabling the detection of present or recent-past RA flare.

The patient perspective was explored by semistructured individual interviews of patients with RA. Two health psychologists conducted a content analysis to extract items best describing flare from the interviews. The physician's perspective was explored through a Delphi exercise conducted among a panel of 13 rheumatologists. A comprehensive list of items produced in the first round was reduced in a four-round Delphi process to select items cited by at least 75% of the respondents. The identified elements were assembled in domains—each converted into a statement—to constitute the final self-administered Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire.

The content of 99 patient interviews was analysed, and 10 domains were identified: joint swelling or pain, night pain, fatigue and different emotional consequences, as well as analgesic intake. The Delphi process for physicians identified eight domains related to objective RA symptoms and drug intake, of which only four were common to domains for patients. Finally, 13 domains were retained in the FLARE questionnaire, formulated as 13 statements with a Likert-scale response modality of six answers ranging from ‘absolutely true’ to ‘completely untrue’.

Two different methods, for patient and physician perspectives, were used to develop the FLARE self-administered questionnaire, which can identify past or present RA flare.

252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands.

In an FOI sequence, three phases could be distinguished (P1–P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls.

ICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.

Both studies were randomised, double-blind, placebo-controlled, parallel-group studies in patients with RA receiving methotrexate or sulphasalazine. Phase IIa was an ascending-dose trial in two cohorts (n=75) using AZD9056 administered daily over 4 weeks. Phase IIb included an open-label etanercept treatment group. Patients were randomised to receive treatment for 6 months with 50, 100, 200 or 400 mg AZD9056 (oral, once a day) or matching placebo (oral, once a day), or subcutaneous etanercept (50 mg once a week).

In phase IIa, 65% of AZD9056 recipients at 400 mg/day responded at the ACR20 level compared with 27% of placebo-treated patients. A significant reduction in swollen and tender joint count was observed in the actively treated group compared with placebo, whereas no effect on acute-phase response was observed. Of 385 randomised patients in the phase IIb study, 383 received treatment. AZD9056 (all doses) had no clinically or statistically significant effect on RA relative to placebo as measured by the proportion of patients meeting the ACR20 criteria at 6 months and further supported by secondary end points. In both studies AZD9056 was well tolerated up to 400 mg/day.

AZD9056 does not have significant efficacy in the treatment of RA, and the P2X₇ receptor does not appear to be a therapeutically useful target in RA.

ClinicalTrials.gov NCT00520572.