The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a
high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evide...
The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a
high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evidence that vitamin D deficiency is common in the general population, and perhaps more so in
chronic pain patients [3].
The relationship that McBeth and colleagues found was not strong, despite the large sample size and impeccable methods; although there was a20-30% increase in risk, the lower confidence interval was only just above
1 in most analyses, and was never larger than 1.1. Such modest association cautions against leaping to conclusions of causality, however beguiling a link between low vitamin D levels and musculoskeletal pain might be.
Most observational studies confirm a tendency to lower vitamin D levels in patients with musculoskeletal pain, but clinical trials (such as there are) change from perhaps suggesting a benefit of treatment to being
quite negative as their methodological quality increases. Support is found mostly in open studies, and those not even randomised [3,4]. Randomised double blind trials are overwhelmingly negative, demonstrating no significant pain relief with vitamin D treatment [3,5].
As it stands no causal link between vitamin D deficiency and chronic pain has been established. McBeth and colleagues hint that physical activity levels and lifestyle of people with musculoskeletal pain may be
important confounders, and certainly the relationship between vitamin D levels and presence of pain diminished as those criteria were used to adjust the logistic regression [1]. It was interesting that in a survey of patients with osteoarthritis and rheumatoid arthritis, only 15 of 68 (22%)
engaged in brisk walking; 30% did no exercise, whilst all other types of exercise noted would almost certainly have been taken indoors [6]. In another survey of 5,235 patients with rheumatoid arthritis only 14% reported physical exercise three or more times per week; most patients
undertook no regular weekly exercise [7]. Given that chronic musculoskeletal pain militates against exercise and spending much time out of doors, it seems likely that any association is not causative.
The presently available evidence is not good enough to answer the clinically important question whether vitamin D helps in chronic pain, especially in which type of patient, and there is clearly a need for more and better studies in this area. Their exact design is a topic worthy of discussion at length and therefore cannot be fully elaborated on here, but obvious issues involve vitamin D preparation, dose, treatment schedule and chronic pain condition [3]. As a first step, comparison with placebo would be essential to establish or refute efficacy of vitamin D in chronic pain, with safety endpoints to enable assessment of benefit versus harm. Trial outcomes and design would need to reflect what is clinically important,
something largely missing in the presently available evidence, but there is some recent guidance for chronic pain trials [8].
References
[1] McBeth J, Pye SR, O'Neill TW, et al. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis Published Online First: 24 May
2010. doi: 10.1136/ard.2009.116053
[2] Knutsen KV, Brekke M, Gjelstad S, et al. Vitamin D status in patients with musculoskeletal pain, fatigue and headache: A cross-sectional descriptive study in a multi-ethnic general practice in Norway. Scand J Prim Health Care. Published Online First: 20 July 2010. doi:
10.3109/02813432.2010.505407
[3] Straube S, Moore RA, Derry S, et al. Vitamin D and chronic pain. Pain 2009;141:10-3.
[4] Straube S, Moore RA, Derry S, et al. Vitamin D and chronic pain in immigrant and ethnic minority patients-investigation of the relationship and comparison with native Western populations. Int J Endocrinol 2010;2010:753075.
5] Straube S, Derry S, Moore RA, et al. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev 2010;(1):CD007771.
[6] Gecht MR, Connell KJ, Sinacore JM, et al. A survey of exercise beliefs and exercise habits among people with arthritis. Arthritis Care Res 1996;9:82-8.
[7] Sokka T, Hakkinen A, Kautiainen H, et al.; QUEST-RA Group. Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum 2008;59:42-50.
[8] Moore RA, Eccleston C, Derry S, et al. for the ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief and the Cochrane Pain Palliative and Supportive Care Systematic Review Group editors. "Evidence" in chronic pain - establishing best practice in the reporting of systematic reviews. Pain, in press. doi:10.1016/j.pain.2010.05.011
In point 5 and 7-8 of the EULAR recommendations for the management of rheumatoid arthritis (1) the following statements are listed:
1) In DMARD naive patients, irrespective of the addition of GCs, synthetic DMARD monotherapy rather than combination therapy of synthetic DMARDs may be applied.
2) If the treatment target is not achieved with the first DMARD strategy, addition of a biological DMARD s...
In point 5 and 7-8 of the EULAR recommendations for the management of rheumatoid arthritis (1) the following statements are listed:
1) In DMARD naive patients, irrespective of the addition of GCs, synthetic DMARD monotherapy rather than combination therapy of synthetic DMARDs may be applied.
2) If the treatment target is not achieved with the first DMARD strategy, addition of a biological DMARD should be considered when poor prognostic factors are present; in the absence of poor prognostic factors, switching to another synthetic DMARD strategy should be considered.
3) In patients responding insufficiently to MTX and/or other synthetic DMARDs with or without GCs, biological DMARDs should be started; current practice would be to start a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab, infliximab) which should be combined with MTX.
Furthermore, in the explanatory details of point 5 it is concluded that neither a start with combinations of synthetic DMARDs nor a step up combination therapy are better than monotherapies or switching DMARDs for the major outcomes.
Consequently the use of combination DMARD therapy for rheumatoid arthritis is more or less dissuaded in these recommendations. The evidence for this advice against combination DMARD therapy is given in a review article from
2005 (2). However, substantial evidence in favour of combination DMARD therapy has appeared since then (3-6).
In the BEST study (3) a direct comparison showed that infliximab combined with methotrexate was better than step-up combination of DMARDs during the first year period in which the treatment was stepped-up to full-dose treatment (difference: -0.68% [-1.01, -0.35], p<0.0001). However, during the second year after attainment of the full doses there was no longer a difference between infliximab combined with methotrexate and conventional combination DMARD therapy (difference: 0.03 [-0.34, 0.40] p =0.87).(4). Consequently this study is in favour of an initial combination DMARD therapy in full doses in order to reach maximum effect as soon as possible, a maximum effect which corresponds to the effect of a biologic with methotrexate. In the BEST study these data are confirmed by
the fourth arm of the study showing that initial combination of DMARDs with glucocorticoid is as effective as infliximab with methotrexate already during the first year (difference: -0.07 [-0.25, 0.11] p = 0.44) (3).
In addition to this evidence in favour of combination DMARD with or without glucocorticoid treatment, our recent meta-analysis of 70 randomised trials using blindly assessed progression in radiographic scoring as outcome (5) shows that 1 DMARD vs. placebo reduces radiographic
progression with a relative effect of 74% per year, that 2 DMARDs vs. one DMARD reduce radiographic progression with additionally 52% and that 3 DMARDs vs. one DMARD reduce radiographic progression with additionally 78%. The last effect corresponds to the effect of a biologic with
methotrexate. An independent meta-analysis finds results comparable to ours (6).
Some may argue that there are more, better and bigger studies of the effects of biologics than the effects of DMARDs and that the evidence for biologics therefore is better. However, with the exception of the BEST study (3,4) all biologic studies are insufficiently designed as they only compare combination therapy vs. monotherapy. They should, of course have compared combination therapy vs. combination therapy. It is unreasonable to base treatment recommendations on wrongly designed studies on the expense of the conventional DMARDs (and the tax payers) just because they are bigger.
In our opinion, the new EULAR recommendations are favouring unreasonably expensive treatments by excluding a cheap and effective treatment principle and should be changed to include combination DMARD therapy in the line before the biologics.
All that said, the authors of the present letter are happy that we have the possibility to use biologics when they are indicated, that is when combination DMARD treatment is not sufficient to control the disease
activity of rheumatoid arthritis.
References
1. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:964-75.
2. Smolen JS, Aletaha D, Keystone E. Superior efficacy of combination therapy for rheumatoid arthritis: fact or fiction? Arthritis Rheum 2005;52:2975-83.
3) Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005;52:3381-90.
4) Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in
early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007;146:406-15.
5) Graudal N, Juergens G. Similar effects of disease modifying anti rheumatic drugs, glucocorticoids and biologics on radiographic progressionin rheumatoid arthritis: meta-analysis of 70 randomised placebo or drug controlled studies including 112 comparisons. Arthritis Rheum. 2010 Jun 17. [Epub ahead of print]
6) Ma MH, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis.Rheumatology (Oxford). 2010;49:91-8.
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive
management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported...
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive
management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported in two trials, failed to show functional gains,' only referring to two negative trials [2-3]. However, Table 1 of their paper shows that in the TICORA
study there were substantial improvements in physical function with intensive therapy (HAQ change -0.97 0.8 versus -0.47 0.9; p=0.0025)[4].
References
1. Schoels M, Knevel R, Aletaha D, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010;69:638-43.
2. Symmons D, Tricker K, Roberts C, et al. The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis. Health Technol Assess
2005;9:iii-iv, ix-x, 1-78.
3. Verstappen SM, Jacobs JW, van der Veen MJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an
open-label strategy trial). Ann Rheum Dis 2007;66:1443-9.
4. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single blind randomised controlled trial. Lancet 2004; 364:263-9.
I read with interest the editorial on modified release (MR) prednisone in patients with rheumatoid arthritis (RA)[1]. In brief, it can be inferred from available data that the only clinical advantage of MR prednisone over immediate release (IR) prednisone was a decrease in duration of morning stiffness [1]. Of note, patients received IR
prednisone in the morning. Due to its short duration of action, low-dos...
I read with interest the editorial on modified release (MR) prednisone in patients with rheumatoid arthritis (RA)[1]. In brief, it can be inferred from available data that the only clinical advantage of MR prednisone over immediate release (IR) prednisone was a decrease in duration of morning stiffness [1]. Of note, patients received IR
prednisone in the morning. Due to its short duration of action, low-dose IR prednisone is inadequate for controlling disease symptoms round-the-clock in patients with RA. In clinical practice, this issue is often settled by dividing the daily dose of IR prednisone every 12 hours [2]. It has been suggested to give half the dose in the morning and half at bedtime [2]. In our department, two thirds of the dose are given in the morning and one third in the evening, to minimize hypothalamic-pituitary-adrenal axis suppression. In our experience, this timing of IR prednisone administration is more effective than the same dose given once a day in the morning. Finally, I wonder whether MR prednisone might be 'a valuable new asset'[1].
References
1. Jacobs JWG, Bijlsma JWJ. Modified release prednisone in patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:1257-9.
2. Conn DL, Lim SS. New role for an old friend: prednisone is a disease-modifying agent in early rheumatoid arthritis. Curr Opin Rheumatol 2003;15:193-6.
De Vries and and Abbing-Karahagopian doubt the validity of the outcomes of our study and state that the myocardial infarction (MI) incidence rate in the control population might be underestimated, as they are much lower than rates found by Koek et al.
However, there seems to be some misunderstanding about what these data represent. Our figures were derived from routine electronic medical records o...
De Vries and and Abbing-Karahagopian doubt the validity of the outcomes of our study and state that the myocardial infarction (MI) incidence rate in the control population might be underestimated, as they are much lower than rates found by Koek et al.
However, there seems to be some misunderstanding about what these data represent. Our figures were derived from routine electronic medical records of GPs that participate in the Netherlands Information Network of General Practice (LINH). As such they include only non-fatal MI, whereas
Koek et al reported non-fatal as well as fatal MI. The non-fatal rate found by Koek is approximately 1.4/1000 person years, and this is completely compatible with the rates reported by LINH (1.0-1.1 per 1000 person years).
Hence, there is no under-estimation of MI in our control group and consequently no selection bias.
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it
lasted only 6 weeks; and these were duly published.[...
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it
lasted only 6 weeks; and these were duly published.[2] The primary report contained data on American College of Rheumatology (ACR) 20, -50 and -70 response rates, European League Against Rheumatism (EULAR) response rates,
Disease Activity Score in 28 joints (DAS28) results and the change in all individual RA core set measures, as recommended by EULAR/ACR reporting guidelines for clinical trials.[3]
The current consise report duplicates the primary report in the presentation of patient pain, patient assessment of disease activity and physical function (Health Assessment Questionnaire), all components of the RA core set. The only new information is in the results of the Short Form-36 questionnaire. It could be argued that 6-week changes in the scores of this questionnaire carry little import for patients with a lifelong disease such as RA, and that improvements in such questionnaires are unsurprising when disease activity is reduced.
The pharmaceutical industry has a legitimate interest in raising awareness for their innovations. Unfortunately, this is often accompanied by 'slicing and dicing' of study results to increase the number of publications. After a dip caused by the coxib disaster, I note this phenomenon is back with a vengeance.
Clinical researchers serving as investigators on industry-sponsored studies have a responsibility to protect the community against duplicate publication and papers/abstracts that carry little or no new information.
This responsibility also extends to peer reviewers, journal editors and abstract selection committees.
References
1. Coombs JH, Bloom BJ, Breedveld FC, et al. Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial. Ann
Rheum Dis 2010;69:413-6.
2. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 2009;60:1895-905.
3. Aletaha D, Landewe R, Karonitsch T, et al. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann Rheum Dis 2008;67:1360-4.
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the
Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared...
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the
Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared self-reported myocardial infarction in a well-defined cohort of AS patients, with MI events from LINH, a Dutch general practice database with electronic health care records. Although it is very difficult to estimate incidence rates of myocardial infarction in the Netherlands, we think that the rates in LINH are substantially underestimated. In LINH, overall incidence rates of MI were 1.0-1.1 / 1000 person years between 2002-2008 [2]. In contrast, when linking primary care with hospitalisation and other registries, incidence
rates of MI were 2-3 times higher in the year 2000: 1.7/1000 person years for women, and 3.0/1000 person years for men [3]. The observed association between AS and MI, may be explained by selection bias, as a result of
substantial under-recording of MIs in the LINH database.
References
1. F. de Vries, C. de Vries, C. Cooper et al. Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database. International
Journal of Epidemiology 2006 35(5):1301-1308.
2. http://www.linh.nl/, accessed 13 March 2010.
3. H.L. Koek, A. de Bruin, A. Gast, et al. Incidence of first acute myocardial infarction in the Netherlands. Neth J Med 2007; 65(11):434-441.
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept
(0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept
(0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
The 'conclusion' that the general "two to threefold" increase is "similar to that expected" may suggest the latter explanation is indeed possible, but seems rather to miss the point and suggests on the part of the authors
either a lack of confidence in their own data or a wish not to offend.
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospec...
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospective,controlled,randomised trial is urgently needed.
There is currently no gold standard measure of disease activity in SSc, which would facilitate clinical trials. The authors refer to a disease activity score in Table 1B, it would be helpful if they explain what score they have used (including a reference).
We thank Dres Arends and Fadini and their coworkers for
their interest in our article and for their comments.
In general, the EUSTAR recommendations are guidelines for research in an evolving field. We fully agree with the statements by Dres Arends and Fadini that these recommendations should not be considered as a final and
definite, but should rather be seen as a first attempt to reach conse...
We thank Dres Arends and Fadini and their coworkers for
their interest in our article and for their comments.
In general, the EUSTAR recommendations are guidelines for research in an evolving field. We fully agree with the statements by Dres Arends and Fadini that these recommendations should not be considered as a final and
definite, but should rather be seen as a first attempt to reach consensus.
It is important to emphasize that further research regarding the differentaspects of EPC biology are crucial and that the EUSTAR recommendations need to be modified in the future based on new results. However, we disagree that recommendation for EPC research should not be made at this
time. The conflicting results, the many different techniques to isolate EPCs and the in part both contradictory and overlapping definitions of EPC
strongly argue for consensus development in this field. The EUSTAR recommendations can be seen as a starting point, on which further discussion and consensus can be developed.
Specifically, Dres Arends and Fadini raise the following points for discussion: First, they argue that there are a variety of EPC subpopulations. We fully agree with this statement. The term “EPCs” defines any precursor cell that can acquire an endothelial phenotype under
certain conditions. Thus, EPCs are defined by functional characteristics and not by morphological markers and include cultured as well as circulating EPCs. Based on this functional definition, the term “EPCs” summarizes a variety of different cell populations as highlighted in more detail in our recent review on EPCs (1). Accordingly, we agree that EPCs defined by the expression of certain markers by FACS and EPCs propagated by certain cell culture conditions are not the same population, but likely
represent different subpopulations.
Secondly, Dres Arends and Fadini argue that for EPC cultures there is no evidence of one coating strategy being superior over another. Again, there is no disagreement on this point. With regards to the culture
conditions for EPCs, we state in the manuscript that “no protocol has been shown to be superior to another. However, as the contents of EGM-2 are best defined, we suggest using this medium for future experiments.
Systematic studies on the different extracellular matrix components for coating of the culture dishes are not available, but we feel that coating with laminin and type IV collagen would be least artificial as they resemble most closely the vascular basal membrane.” Thus, we already clearly indicated in the initial manuscript that the recommendation on medium and coating are based on expert opinion. We would like to further emphasize that a comparison of different coating strategies should be
listed high on the research agenda and that the results of such experiments might lead to changes in our recommendations.
Thirdly, it is argued that an enriched cell population might lead to low number of events, and thus to a higher coefficient of variability. To avoid this bias, our guidelines state that the collection of a large number of events is mandatory. Regarding the depletion of immature cells before FACS together with the use of a viability marker, we agree that this protocol need to be fully validated before being established as the gold standard. Indeed, the best marker for depletion in particular is not known. However, the use of lin- and 7AAD allowed us to
show an association between the number of EPCs detected by flow cytometry (Lin–/7AAD–/CD34+/CD133+/VEGFR-2+) and the formation of late outgrowth colonies in patients with systemic sclerosis and also a correlation between the number of EPCs and the number of colony-forming units (2).
With regards to the specific point of the viability marker that is unambiguously warranted for the quantification of immature cells, it would be of interest to know which marker is used by Fadini et al and which definition was used for immature monocluear cells.
However, we confirm that in SSc or rheumatoid arthritis patients as well as in controls, the majority of gated lin- CD34+CD133+KDR+ are frequently 7AAD+ and thus
represent dead cells. We assume that this does not relate to therapies, but do have no other explanation yet for this finding. Further improvements in the accuracy of detection or mechanism leading to high number of circulating dead cells are welcome.
References
1. Distler JHW, Beyer C, Schett G, et al. Endothelial Progenitor Cells: Novel players in the pathogenesis of
rheumatic diseases. Arthritis Rheum, in press.
2. Avouac J, Juin F, Wipff J et al. Circulating endothelial progenitor cells in systemic sclerosis: association with disease severity. Ann Rheum Dis
2008;67(10):1455-60.
Dear Editor,
The article by McBeth et al. [1] demonstrated a limited association of low levels of vitamin D with musculoskeletal pain in men. Another recent study from a multi-ethnic general practice in Norway also showed a high prevalence of hypovitaminosis D in patients with non-specific musculoskeletal pain, headache, or fatigue for whom the GP had suspected a low vitamin D level [2]. This adds to previous evide...
Dear Editor,
In point 5 and 7-8 of the EULAR recommendations for the management of rheumatoid arthritis (1) the following statements are listed:
1) In DMARD naive patients, irrespective of the addition of GCs, synthetic DMARD monotherapy rather than combination therapy of synthetic DMARDs may be applied.
2) If the treatment target is not achieved with the first DMARD strategy, addition of a biological DMARD s...
Dear Editor,
Many thanks to Schoels et al for their very helpful systematic literature review of the evidence for treating RA to target [1]. However, I am concerned that the authors' discussion may lead readers to conclude erroneously that there is no evidence that treat to target, intensive management has a beneficial impact on physical function. In their discussion the authors state that 'Functional outcomes, reported...
Dear Editor,
I read with interest the editorial on modified release (MR) prednisone in patients with rheumatoid arthritis (RA)[1]. In brief, it can be inferred from available data that the only clinical advantage of MR prednisone over immediate release (IR) prednisone was a decrease in duration of morning stiffness [1]. Of note, patients received IR prednisone in the morning. Due to its short duration of action, low-dos...
Dear Editor,
De Vries and and Abbing-Karahagopian doubt the validity of the outcomes of our study and state that the myocardial infarction (MI) incidence rate in the control population might be underestimated, as they are much lower than rates found by Koek et al.
However, there seems to be some misunderstanding about what these data represent. Our figures were derived from routine electronic medical records o...
Dear Editor,
Dear editor,
I was disappointed in the publication of the concise report on the effects of an orally active Janus kinase (JAK) inhibitor on patient-reported outcomes in rheumatoid arthritis (RA). [1] JAK inhibition represents a new treatment option with potential in RA, so the results of the proof-of-concept trial were of interest, even though it lasted only 6 weeks; and these were duly published.[...
Dear Editor,
Dr Peters and co-workers conducted a case-control study, which showed that myocardial infarction (MI) was a 2-3-fold increased in patients with ankylosing spondylitis (AS). They compared AS patients to a sample of the Dutch general population. We are concerned that the association is (largely) explained by inappropriate selection of controls, instead of reflecting a causal pathway [1]. The authors compared...
Dear Editor,
This is an interesting paper; however I was surprised at the vagueness of the conclusion. The authors showed a significantly increased 'ratio of lymphoma' with adalimumab (4.1) and infliximab (3.6) vs. entanercept (0.9). Unless some confounding variable is discovered, the conclusion would seem clear. Either adalimumab and infliximab predispose to lymphoma, or entanercept prevents it.
The 'conclusion'...
Dear Editor,
I read with interest the article by Smith et al, which provides encouraging data on safety and potential efficacy of rituximab in a subset of patients with diffuse cutaneous systemic sclerosis (DcSSc). It lends support to the concept that B-cell depletion could be a relatively safe and effective strategy DcSSc. The effects on skin thickening differ from those published by Lafyatis et al, indicating a prospec...
Dear Editor,
We thank Dres Arends and Fadini and their coworkers for their interest in our article and for their comments.
In general, the EUSTAR recommendations are guidelines for research in an evolving field. We fully agree with the statements by Dres Arends and Fadini that these recommendations should not be considered as a final and definite, but should rather be seen as a first attempt to reach conse...
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