A recent clinical study in mothers with rheumatoid arthritis (RA)
published in this journal, reported that high maternal serum levels of
interleukin-6 (IL-6) is associated with low birth weight deliveries1. Low
birth weight in turn is associated with impaired growth during childhood2.
Interestingly, overexpression of IL-6 leads to reduced bone growth in
mice3. Although the systemic effects of IL-6...
A recent clinical study in mothers with rheumatoid arthritis (RA)
published in this journal, reported that high maternal serum levels of
interleukin-6 (IL-6) is associated with low birth weight deliveries1. Low
birth weight in turn is associated with impaired growth during childhood2.
Interestingly, overexpression of IL-6 leads to reduced bone growth in
mice3. Although the systemic effects of IL-6 are well understood, any
local effects on the growth plate have not yet been clarified. Aiming to
study the local actions of IL-6, we isolated fetal rat metatarsal bones
and cultured them ex vivo for 12 days while monitoring bone growth. When
exposed to IL-6 and its soluble receptor IL-6R alpha (10+100 ng/ml),
growth was decreased by 21.1% compared to control (p<0.001) (Figure
1A). IL-6 mainly targeted the hypertrophic growth plate zone, reducing its
height by 53.7% and area by 72.6% (p<0.05 vs. control; Figure 1B).
These data further strengthen the above cited report of an association
between high maternal IL-6 levels and impaired fetal growth1.
Beside IL-6, the proinflammatory cytokines IL-1 beta and TNF-alpha
are often up-regulated in RA patients. To investigate any interaction
between these cytokines, fetal rat metatarsal bones were cultured with IL-
6+IL-6R alpha (10+100 ng/ml) in combination with IL-1beta (10 ng/ml) or
TNF-alpha (10 ng/ml). Growth was then found to be reduced by 40.6% and
54.0%, respectively (p<0.001 vs. control) (Figure 1A). In supernatants
of bones cultured with IL-1 beta and TNF-alpha in combination, a 27-fold
increase in IL-6 production was measured while individually these
cytokines only marginally affected IL-6 production (Figure. 2). Thus, IL-1
beta and TNF-alpha act in synergy to induce local IL-6 production in
growth plate cartilage; an effect which may explain the synergistic growth
suppressive effect of IL-1? and TNF-alpha previously reported in cultured
fetal rat metatarsal bones4 5.
Tocilizumab, a humanized anti-IL-6R monoclonal antibody preventing IL
-6 binding to the IL-6R6, provides sustained clinical improvement and a
favourable risk-benefit profile in children with RA7. However, to date it
is unclear if anti-IL-6 treatment can rescue bone growth in these
patients. To experimentally address this gap of knowledge, we co-cultured
fetal rat metatarsal bones with IL-6 antibody (2.5 micrograms/ml) and the
detrimental IL-1 beta+TNF-alpha combination for 12 days, but growth could
not be reconstituted. This failure, which could be due to difficulties for
the IL-6 antibody to penetrate into the growth plate, emphasizes the
importance to develop small molecules/peptides directed towards the
blocking of IL-6 production or signalling allowing bone growth to be
rescued.
In conclusion, we here report the novel finding that IL-6 acts
directly at the growth plate level to suppress bone growth and that IL-
1beta and TNF-alpha synergistically trigger this effect by markedly
stimulating the local production of IL-6. Our experimental data strengthen
the recent clinical report of an association between high maternal IL-6
levels and impaired fetal growth.
References
1. de Steenwinkel FD, Hokken-Koelega AC, de Man YA, et al. Circulating maternal cytokines influence fetal
growth in pregnant women with rheumatoid arthritis. Ann Rheum Dis 2012.
2. Cutfield WS, Regan FA, Jackson WE, et al. The endocrine consequences for very low birth weight
premature infants. Growth Horm IGF Res 2004;14 Suppl A:S130-5.
3. De Benedetti F, Rucci N, Del Fattore A, et al. Impaired skeletal development in interleukin-6-transgenic mice:
a model for the impact of chronic inflammation on the growing skeletal
system. Arthritis Rheum 2006;54(11):3551-63.
4. Martensson K, Chrysis D, Savendahl L. Interleukin-1beta and TNF-
alpha act in synergy to inhibit longitudinal growth in fetal rat
metatarsal bones. J Bone Miner Res 2004;19(11):1805-12.
5. MacRae VE, Farquharson C, Ahmed SF. The restricted potential for
recovery of growth plate chondrogenesis and longitudinal bone growth
following exposure to pro-inflammatory cytokines. J Endocrinol
2006;189(2):319-28.
6. Mihara M, Kasutani K, Okazaki M, et al. Tocilizumab inhibits signal transduction mediated by both mIL-6R
and sIL-6R, but not by the receptors of other members of IL-6 cytokine
family. Int Immunopharmacol 2005;5(12):1731-40.
7. Yokota S, Imagawa T, Mori M, Efficacy and safety of tocilizumab in patients with systemic-onset
juvenile idiopathic arthritis: a randomised, double-blind, placebo-
controlled, withdrawal phase III trial. Lancet 2008;371(9617):998-1006.
Figures for this eLetter can be found at the ePage with the ARD issues.
With interest we read the article of Sciré et al.,(1) evaluating the
association between remission and mortality in patients with inflammatory
polyarthritis (IP). This study shows that patients achieving remission
early in the disease course, have an improved survival rate compared to
patients never achieving remission. Based on this observation the authors
conclude that achieving remission early in t...
With interest we read the article of Sciré et al.,(1) evaluating the
association between remission and mortality in patients with inflammatory
polyarthritis (IP). This study shows that patients achieving remission
early in the disease course, have an improved survival rate compared to
patients never achieving remission. Based on this observation the authors
conclude that achieving remission early in the disease influences the long
-term outcome. The question arises which processes underlie their
observation. Rheumatoid Arthritis (RA) has been associated with an
increased mortality risk, which has been attributed to the effects of long
-term inflammation.(2) We hypothesized that the observation in which
patients with remission have an improved survival rate, might actually be
driven by the association between prolonged inflammation and increased
mortality risk.
We addressed this hypothesis by taking advantage of long-term outcomes of
556 patients with early undifferentiated arthritis (UA) or RA that were
included in the Leiden EAC between 1993-1998.(3) Treatment in this era was
delayed and DMARDs were mild. We previously observed that patients
included in this era had an increased mortality rate compared to the
general Dutch population(4); an effect which was not present in patients
that were diagnosed more recently and treated more aggressively.(4)
Presently, we evaluated the remission status in relation to mortality. In
our study remission was defined as the persistent absence of synovitis for
at least one year after cessation of contingent DMARD-therapy. This is the
most stringent definition of remission and differs of the definitions used
by Sciré et al., which were based on the number of tender and swollen
joints at a point in time. Presence of DMARD-free sustained remission was
assessed within 3 years after inclusion (similar to Sciré et al.) and also
at any point during follow-up (median 15 years, IQR 13.2-17.1). Mortality
data on patients were tracked nationally using the civic registries
(Gemeentelijke Basis Administratie). First, mortality rates were compared
between patients with versus patients without remission, similar as
performed by Sciré et al. Secondly, we compared the mortality rates of
both groups with the mortality rates of the general Dutch population.
Kaplan Meier-curves were constructed. Cox proportional hazard regression
models for multivariable comparisons were made; all analyses were
adjusted for age and sex. Subsequent adjustments were made also for
rheumatoid factor and smoking (ever versus never). Patients were censored
at date of death or 1st May 2012 whichever came first. Standardized
mortality ratios (SMR) were calculated using the general Dutch population
matched on age, sex and inclusion year (Statistics Netherlands).
Out of 556 patients, 162 (29%) patients died during the total follow-up of
7,682 person years. The mean age was 52.6?17.2, 60% was female. DMARD-free
sustained remission was achieved in 124 (22%) patients within 3 years
after inclusion and in 182 (33%) patients during the total follow-up.
Patients that achieved remission within 3 years had a reduced mortality
compared to patients without remission (HR 0.49 95%CI 0.32-0.75), also
after additional adjustments for rheumatoid factor and smoking (HR 0.60
95%CI 0.39-0.93). Likewise, patient that achieved remission at any point
during follow-up had a lower mortality risk (HR 0.41 95%CI 0.28-0.60 and
HR 0.50 95%CI 0.33-0.74, respectively)
Next we questioned whether patients with remission had a decreased
mortality rate compared to the general Dutch population and/or whether
patients without remission had an increased mortality rate.
We therefore
compared the mortality rates of both patients groups to the mortality
rates of matched controls from the general Dutch population. Patients who
did not achieve remission during three years of disease or during the
total follow-up duration had an significantly increased mortality rate
(SMR 1.49 95% CI 1.26-1.76 and 1.66 95%CI 1.40-1.98 respectively). Patients that achieved remission within the first three years or the
total follow-up duration did not have an increased mortality (SMR 0.70 95%
CI 0.47-1.02 and SMR 0.66 0.47-0.92 respectively).
In conclusion, we studied the relation between DMARD-free sustained
remission and mortality. Similar as Sciré et al. we observed that patients
that achieve remission have an improved survival compared to patients
without remission. Furthermore, when using the general population as a
reference, we observed that patients with persistent arthritis had 49-66%
increased mortality risk. This is in line with previous observations , in
these patients and in other studies, which show that rheumatoid arthritis
is associated with a decreased survival.(1;4) This increased mortality
risk was no longer present in patients that achieved DMARD-free sustained
remission, indicating that the survival probability returns to normal in
patients that are cured from RA. In our view the slightly decreased SMR in
these patients can be explained by a healthy inclusion bias or by good
medical care while being under specialist's control.(4)
References
(1) Sciré CA, Lunt M, Marshall T, et al. Early remission is
associated with improved survival in patients with inflammatory
polyarthritis: results from the Norfolk Arthritis Register. Ann Rheum Dis
2013 Jun 7;Epub ahead of print doi:10.1136/annrheumdis-2013-203339 .
(2) Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis:
2008 update. Clin Exp Rheumatol 2008;26(5 Suppl 51):S35-S61.
(3) de Rooy DP, van der Linden MP, Knevel R, et al. Predicting
arthritis outcomes--what can be learned from the Leiden Early Arthritis
Clinic? Rheumatology (Oxford) 2011;50(1):93-100.
(4) van Nies JA, de Jong Z., van der Helm-van Mil AH, et al.
Improved treatment strategies reduce the increased mortality risk in early
RA patients. Rheumatology (Oxford) 2010;49(11):2210-6.
We would like to reply to the recent letter by Murphy et al(1)
regarding the possible influence of obesity and weight changes on the
results of the SEKOIA trial of the efficacy and safety of strontium
ranelate in knee osteoarthritis.2 Obesity and overweight are recognized
risk factors for osteoarthritis,3 and so it is essential to include such
patients in studies of potential treatments, since they are...
We would like to reply to the recent letter by Murphy et al(1)
regarding the possible influence of obesity and weight changes on the
results of the SEKOIA trial of the efficacy and safety of strontium
ranelate in knee osteoarthritis.2 Obesity and overweight are recognized
risk factors for osteoarthritis,3 and so it is essential to include such
patients in studies of potential treatments, since they are likely to
constitute a substantial proportion of the patients who could hope to
benefit from treatment. Almost half of the patients in SEKOIA were obese
at baseline (44% had body mass index [BMI] ?30 kg/m2) with no relevant
differences between the three treatment groups: 45% for the patients
receiving strontium ranelate 1 g/day; 43% for strontium ranelate 2 g/day;
and 44% for placebo. There was no significant variation in body weight
over the 3 years of the trial in any of the treatment groups (mean changes
were +0.20?4.42, +0.22?4.84, and -0.46?6.35 kg, respectively) and
adjustment of the main study results for obesity did not produce
substantial changes in the results on joint space narrowing (JSN) with
strontium ranelate (treatment-placebo difference in JSN [mm] adjusted for
obesity: E(SE) 0.10 (0.04), 95% CI 0.02-0.19, p=0.016 for 2 g/day;
treatment-placebo difference in JSN [mm] not adjusted for obesity: E(SE)
0.10 (0.04), 95% CI 0.02-0.19, p=0.018 for 2 g/day). Moreover, to
ascertain the absence of a relationship between weight and JSW changes,
JSN was evaluated according to quartiles of weight change, independently
of treatment group, and the results did not show any obvious relationship
(change in JSW in the lowest quartile [weight loss <2kg]: -0.33?0.68,
change in JSW in the highest quartile [weight gain > 2.3 kg]: -
0.30?0.53 mm, respectively). No studies have been conducted to date to
assess the efficacy of strontium ranelate combined with weight reduction;
and there are no such data available in SEKOIA. However, we agree that
weight control, and reduction when needed, and exercise are essential
components of the management strategy of patients with knee osteoarthritis
and could be associated with strontium ranelate treatment.
References
1. Murphy C-L, Murphy E, Duffy T et al. Efficacy and safety
of oral strontium ranelate for the treatment of knee osteoarthritis:
results of a randomised double-blind, placebo-controlled trial. Ann Rheum
Dis 2013;72:e13.
2. Reginster J-Y, Badurski J, Bellamy N et al. Efficacy and
safety of oral strontium ranelate for the treatment of knee
osteoarthritis: results of a randomised double-blind, placebo-controlled
trial. Ann Rheum Dis 2013;72:179-86.
3. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update
with relevance for clinical practice. Lancet 2011;377:2115-26.
“A finger in the wound” is put by Condon et al. in their very interesting paper treating severe lupus nephritis with rituximab and mycophenolate, additionally to i.v. methyl-prednisolone, but not long-term oral steroids, achieving a good clinical response in most patients. 1
Rheumatologists and nephrologists have the notion that glucocorticoids are the cornerstone for the treatment of autoimmune disea...
“A finger in the wound” is put by Condon et al. in their very interesting paper treating severe lupus nephritis with rituximab and mycophenolate, additionally to i.v. methyl-prednisolone, but not long-term oral steroids, achieving a good clinical response in most patients. 1
Rheumatologists and nephrologists have the notion that glucocorticoids are the cornerstone for the treatment of autoimmune diseases, particularly lupus nephritis, where steroids are considered the base of the therapeutic pyramid. Recently, and according to the absence of controlled studies and no agreement regarding the best dosage of steroids to achieve clinical and histological remission, this old accepted paradigm could be not further accepted.2,3
Several years ago, our group reported an open trail study including patients with refractory lupus nephritis with not use steroids (6 out of 22) and in most of the others the doses of glucocorticoids were not increased, showing most of patients an adequate clinical and immunological response to variable-low doses of rituximab.4 These results are not limited to lupus nephritis, reaching adequate responses without conventional doses of steroids in haematological, neurological and other lupus manifestations, as well as in different connective tissue diseases (inflammatory immune myositis, primary vasculitis). In addition, this type of therapeutic response was also observed in patients that had been receiving immunosuppressive therapy and presented a relapse.
Therefore, our data further support the main conclusion of the study of Condon et al. stating that oral steroids can be avoided without affecting the effectiveness of immunosuppressive therapy in lupus nephritis and other autoimmune inflammatory conditions. In addition, it is expected that those patients not receiving long-term oral steroids show a diminished frequency of osteoporosis, cataracts and ischemic bone necrosis. The possibility to include other therapeutic arms with variable doses of rituximab could be interesting, moreover because B cell depletion can be induced with low doses, as we emphasized previously. 4,5
References
1. Condon MB, Ashby D, Pepper RJ, et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis 2013;0:1–7. doi: 10.1136/annrheumdis-2012-202844
2. Fischer-Betz R, Chehab G, Sander O, et al. Renal outcome in patients with lupus nephritis using a steroid-free regimen of monthly intravenous cyclophosphamide: a prospective observational study. J Rheumatol. 2012; 39: 2111–7.
4. Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther. 2006; 8(3): R83. Published online 2006 May 5. doi: 10.1186/ar1954
PMCID: PMC1526618
5. Abud-Mendoza C, Moreno-Valdés R, Cuevas-Orta E, Borjas A, et al. Treating severe systemic lupus erythematosus with rituximab. An open study. Reumatol Clin. 2009;5(4):147-52.
We read with interest the article on the impact of gender on outcomes
in ankylosing spondylitis [1]. In their analysis of four controlled
clinical trials, the authors found a higher burden of ankylosing
spondylitis (AS) in female patients and less improvement in outcome
measures compared with men, "despite women having a later disease onset
and shorter disease duration". They conclude that the mechanism...
We read with interest the article on the impact of gender on outcomes
in ankylosing spondylitis [1]. In their analysis of four controlled
clinical trials, the authors found a higher burden of ankylosing
spondylitis (AS) in female patients and less improvement in outcome
measures compared with men, "despite women having a later disease onset
and shorter disease duration". They conclude that the mechanism behind
this observation is unclear and additional research is necessary.
Regrettably, the authors take the age at diagnosis as "disease onset" and
ignore all the years in which the disease was not diagnosed correctly and
did not get appropriate treatment. Because of the high prevalence of a
long delay in diagnosis in the case of ankylosing spondylitis, the
Assessment of SpondyloArthritis international Society (ASAS) concluded at
their workshop in 2006 that the duration since diagnosis should never be
called "disease duration" in the case of ankylosing spondylitis [2, 3]. As
has been shown in [4, 5], the average age at disease onset (first symptoms
of AS) does not differ significantly between male and female patients with
AS, whereas the average delay in diagnosis is significantly larger in
females (9,8 years compared to 8.4 years in males, p<0.01 [5]).
A worse outcome in connection with a longer delay in diagnosis and a
longer inappropriate treatment is not really surprising. It does not occur
"despite a later disease onset" as stated in [1]. In contrast, the longer
delay in diagnosis may well - besides other gender differences -
contribute to the observed difference in disease outcome.
In this connection it may be of interest that it has also been reported in
the literature that the ankylosis progresses faster on average in male
patients with AS than in females, connected with a higher prevalence of
severe pain after a long disease duration in female patients, however not
in males [5, 6]. This difference between genders might be the main
contribution to the observation reported in [1].
References
1. van der Horst-Bruinsma IE, Zack DJ, Szumski A, et al. Female
patients with ankylosing spondylitis: analysis of the impact of gender
across treatment studies. Ann Rheum Dis 2013;72:1221-1224.
2. Feldtkeller E, Erlendsson J. The definition of disease duration in
ankylosing spondylitis: Comment on the article by Davis et al. Ann Rheum
Dis eletter http://www.annrheumdis.com/cgi/eletters/65/11/1518#726, (12
Jul 2006)
3. Feldtkeller E, Erlendsson J. Definition of disease duration in
ankylosing spondylitis. Rheumatol Int 2008;28:693-696.
4. van der Linden S.M., Valkenburg H.A., de Jongh B.M., et al. The
risk of developing ankylosing spondylitis in HLA-B27 positive individuals.
Arthritis Rheum 1984;27:241-249.
5. Feldtkeller E, Bruckel J, Khan MA. Scientific contributions of
ankylosing spondylitis patient advocacy groups, Curr Opin Rheumatol
2000;12:
239-247.
6. Zink A, Braun J, Listing J, et al. Disability and handicap in rheumatoid arthritis and
ankylosing spondylitis - results from the German rheumatological database.
J Rheumatol 2000;27:613-622.
We read with great interest the open clinical trial of four relapsing
polychondritis (RP) patients treated with abatacept by Peng and Rodriguez
recently published in the Annals of the Rheumatic Diseases (1). Indeed, as
the authors pointed out, there is rational to block T-cell pathway in this
disease, though the biologic agents most used as second-line therapy after
corticosteroids (CS) are pro-inflamm...
We read with great interest the open clinical trial of four relapsing
polychondritis (RP) patients treated with abatacept by Peng and Rodriguez
recently published in the Annals of the Rheumatic Diseases (1). Indeed, as
the authors pointed out, there is rational to block T-cell pathway in this
disease, though the biologic agents most used as second-line therapy after
corticosteroids (CS) are pro-inflammatory cytokines blockers as TNF
inhibitors or tocilizumab (2). Of note, rituximab seems not efficient in
this disease (3).
Despite this rational, the study by Peng and Rodriguez is the first
report of abatacept use in RP since we reported a first case in 2010 (4).
Results from this nice small clinical trial using abatacept subcutaneously
at the dose of 125 mg weekly are mitigated: three patients experienced a
considerable improvement on ENT chondritis and on swollen and tender joint
counts. Nevertheless, two patients developed severe central nervous system
and pulmonary involvement at week 2 and 8 respectively. Both had a
history of such organ involvement. CS-sparing is an important issue not
assessed in this trial but three patients were exposed to only 10 mg of
prednisone per day, and the last one was not exposed to CS at abatacept
initiation. The follow-up was limited to 24 weeks.
We would like to share our experience as to complete these results.
Indeed, three adult RP patients have been treated with abatacept in our
department - the data of two of them until mid-2012 have been previously
presented (5). In all cases, abatacept was started because of CS-dependant
or CS-resistant disease. All had ENT chondritis and peripheral arthritis
without internal organ involvement. As ethically mandatory in France, the
decision to treat these patients with off-label abatacept was decided
during a multidisciplinary board associating specialist physicians and
pharmacists. The patients gave their formal consent after explanation of
the expected benefit-to-risk ratio. Abatacept was used intravenously at
the dose of 750 mg at Day0, Day14 and Day30 and then monthly. Efficacy and
adverse drug reactions (ADRs) were colligated in the medical files.
Complete response, partial response and no response were respectively
defined as the complete disappearance, the improvement and the lack of
improvement (or the worsening) of clinical symptoms according to the
physician assessment.
The first patient was a 53-year-old woman who had CS-resistant
disease which had failed to dapsone, methotrexate, and three TNF-
inhibitors. Abatacept was introduced in August 2008 in combination with
dapsone (100 mg/day) and methotrexate (15 mg/week). A complete response
was obtained within four months (4). CS (initially, 40 mg/day of
prednisone) were tapered and stopped within four months. In April 2011,
RP signs reappeared with persistent moderate activity. Abatacept was
replaced with certolizumab, which had no effect. Abatacept was then
reintroduced three months later, leading again to a complete response. No
attempt to space out the infusions has been made until now. One serious
adverse event occurred: skin cellulitis in mid-2010, cured with oral
antibiotics. The second patient was a 62 year-old woman who had not been
improved with adalimumab, infliximab and anakinra. She has been exposed to
abatacept during 12 months leading to a partial response. CS could be
tapered from 60 mg/d to 10 mg/d. No ADR occurred. The drug was then
switched to tocilizumab. The third patient was a 39 year-old man who had
RP associated with chronic discoid lupus erythematosus. Methotrexate was
not efficient. Abatacept was stopped after three months because of
insufficient response. CS could not be tapered (12.5 mg/d). No ADR
occurred.
As a result, our experience suggests also moderate to important
efficacy of abatacept on ENT chondritis and arthritis. CS-sparing was
noteworthy in 2/3 patients and the drug was well-tolerated, even when
exposure lasted 1 to 5 years. Patients did not experienced internal organ
flare as reported by Peng and Rodriguez, but contrarily to their patients:
1) none of ours had a previous history of such internal organ involvement,
2) we used intravenous, not sub-cutaneous abatacept with the classical
loading regimen of 750 mg, three infusion two weeks apart, and 3) our
patients were exposed to higher doses of CS at abatacept initiation.
We totally agree with Peng and Rodriguez regarding the fact that
prospective surveys with validated scale assessment (6) should be
encouraged to assess efficacy and safety of biologics in RP.
Funding: no external source of funding.
Conflict of interest: none
References
1. Peng SL, Rodriguez D. Abatacept in relapsing polychondritis. Ann Rheum
Dis 2013;72:1427-9.
2. Kemta Lekpa F, Kraus VB, Chevalier X. Biologics in relapsing
polychondritis: a literature review. Semin Arthritis Rheum 2012;41:712-9.
3. Leroux G, Costedoat-Chalumeau N, Brihaye B, et al. Treatment of
relapsing polychondritis with rituximab: a retrospective study of nine
patients. Arthritis Rheum 2009;61:577-82.
4. Moulis G, Sailler L, Astudillo L, et al. Abatacept for relapsing
polychondritis. Rheumatology (Oxford) 2010;49:1019.
5. Moulis G, Sailler L, Pugnet G, et al. Biologics in relapsing
polychondritis: a single center case-series. Arthritis Rheum 2012;64:S816-
7.
6. Arnaud L, Devilliers H, Peng SL, et al. The Relapsing Polychondritis
Disease Activity Index: development of a disease activity score for
relapsing polychondritis. Autoimmun Rev 2012;12:204-9.
Dear editor,
A recent clinical study in mothers with rheumatoid arthritis (RA) published in this journal, reported that high maternal serum levels of interleukin-6 (IL-6) is associated with low birth weight deliveries1. Low birth weight in turn is associated with impaired growth during childhood2. Interestingly, overexpression of IL-6 leads to reduced bone growth in mice3. Although the systemic effects of IL-6...
Dear editor,
With interest we read the article of Sciré et al.,(1) evaluating the association between remission and mortality in patients with inflammatory polyarthritis (IP). This study shows that patients achieving remission early in the disease course, have an improved survival rate compared to patients never achieving remission. Based on this observation the authors conclude that achieving remission early in t...
Dear Editor,
We would like to reply to the recent letter by Murphy et al(1) regarding the possible influence of obesity and weight changes on the results of the SEKOIA trial of the efficacy and safety of strontium ranelate in knee osteoarthritis.2 Obesity and overweight are recognized risk factors for osteoarthritis,3 and so it is essential to include such patients in studies of potential treatments, since they are...
Dear Editor,
“A finger in the wound” is put by Condon et al. in their very interesting paper treating severe lupus nephritis with rituximab and mycophenolate, additionally to i.v. methyl-prednisolone, but not long-term oral steroids, achieving a good clinical response in most patients. 1
Rheumatologists and nephrologists have the notion that glucocorticoids are the cornerstone for the treatment of autoimmune disea...
Dear Editor,
We read with interest the article on the impact of gender on outcomes in ankylosing spondylitis [1]. In their analysis of four controlled clinical trials, the authors found a higher burden of ankylosing spondylitis (AS) in female patients and less improvement in outcome measures compared with men, "despite women having a later disease onset and shorter disease duration". They conclude that the mechanism...
Dear Editor,
We read with great interest the open clinical trial of four relapsing polychondritis (RP) patients treated with abatacept by Peng and Rodriguez recently published in the Annals of the Rheumatic Diseases (1). Indeed, as the authors pointed out, there is rational to block T-cell pathway in this disease, though the biologic agents most used as second-line therapy after corticosteroids (CS) are pro-inflamm...
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