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Objective To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.Methods Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.Results We enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance.Conclusion The analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.

Introduction Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF.Methods and analysis The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle.Ethics and dissemination Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA.Trial registration number NCT03445845 and EudraCT2017-004700-22.

Objective To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA).Methods Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome).Results A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference.Conclusion MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.

Abstract Introduction This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib. Methods FINCH 1–3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 response and low disease activity/remission according to Disease Activity Score 28 using C-reactive protein. The exposure-adjusted incident rate (EAIR) of adverse events (AEs) was assessed by baseline BMI, using integrated data from the FINCH 1–4 and the phase 2 DARWIN 1–3 studies (total filgotinib exposure = 8085 patient-years). Results Mean change from baseline in BMI over time was similar across treatment arms. In most patients, BMI increased by ≤ 1 or 2 kg/m2 at both weeks 12 and 24, regardless of treatment group or baseline BMI; few patients had increases of ≥ 4 kg/m2. For most efficacy measures, filgotinib 200 mg was more efficacious than filgotinib 100 mg or active comparators or placebo across BMI subgroups. For the higher filgotinib dose, the EAIR of serious treatment-emergent AEs, venous thrombotic and embolic events, and major adverse cardiovascular events increased with increasing BMI. Conclusions Filgotinib did not lead to substantial changes in BMI, and BMI did not appear to affect the efficacy of filgotinib. Trial Registration ClinicalTrials.gov identifiers: NCT02889796, NCT02873936, NCT02886728, NCT03025308, NCT01888874, NCT01894516, NCT02065700.

Abstract Background Although the advent of new therapeutics for juvenile idiopathic arthritis (JIA) patients has considerably lessened the impact of the disease and reduced its sequelae, the outcomes of JIA remain important in their lives. Disease repercussions and side effects of treatments may affect sexual health and cause psychological distress. This aim of the study was to determine the expectations of adolescent JIA patients and the perceptions of their parents regarding knowledge and communication with healthcare providers (HCPs) in the field of sexual health (SH). Methods In France, from September 2021 to April 2022, a survey was conducted, using anonymous self-administered questionnaires, among JIA patients (adults (aged 18–45 years) to provide insights from their recollection of their adolescence) and their parents in nine rheumatology centers and three patient associations. Results The responses to the 76 patient questionnaires and 43 parent questionnaires that were collected were analyzed. Half of the patients thought JIA impacted their romantic relationships, but the results were less clear-cut for their sexual activity; and 58.7% of the patients said they would be comfortable discussing the subject with HCPs, but only 26.3% had done so, mainly regarding biomedical issues. The patients and their parents thought that ideally, the topic should be addressed in an individual patient education session at the hospital (51.3% and 34.9%, respectively), in a regular consultation (47.4% and 53.5%), or in a dedicated consultation requested by the adolescent without the adolescent’s parents being informed (38.2% and 20.9%). Most of the respondents thought HCPs should be proactive in SH (77.6% of the patients and 69.8% of their parents). More patients than parents said the following digital information tools must be used: videos (29.0% vs. 9.3%, p = 0.0127) and smartphone applications (25.0% vs. 9.3%, p = 0.0372). Conclusion HCPs should consider addressing the unmet need for SH discussions during their patient encounters. To meet this need, we propose concrete actions in line with the wishes of patients and parents. Clinical trial registration number NCT04791189.

Objective To compare the 1-year retention rate of secukinumab in axial spondyloarthritis (axSpA) and its predisposing factors with regard to its time of initiation (eg, right after or remotely from its launch).Methods Study design: Retrospective multicentre French study of patients with axSpA. Study periods: Two cohorts were evaluated regarding the time of initiation of secukinumab: cohort 1 (C1)—between 16 August 2016 and 31 August 2018—and cohort 2 (C2)—between 1 September 2018 and 13 November 2020. Statistical analysis: The 1-year retention rate of secukinumab was estimated using the Kaplan-Meier method, and the log-rank test was used to compare the retention curves of the two cohorts. Preselected factors (eg, disease characterristics, line and time of secukinumab initiation) of secukinumab retention at 1 year were analysed by univariate and multivariate Cox model regression.Results In total, 906 patients in C1 and 758 in C2 from 50 centres were included in the analysis. The 1-year retention rate was better in C2 (64% (61%–68%)) vs C1 (59% (55%–62%)) (HR=1.19 (1.02–1.39); p=0.0297). In the multivariate analysis, the line of biologic therapy was the single predictive factor of the 1-year retention rate of secukinumab picked up in both cohorts, with a better retention rate when prescribed as first-line biologic therapy.Conclusion The better secukinumab retention rate remotely from its launch is explained by its use at an earlier stage of the disease, suggesting a change in the behaviour of prescribing physicians. Our results emphasise the relevance of iterative evaluations of routine care treatments.

Objective To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA).Methods In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Results Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)).Conclusion The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Objectives To analyse glucocorticoid (GC) use and trajectories in a real-life cohort of rheumatoid arthritis (RA).Methods Patients with RA included in the longitudinal RCVRIC cohort for initiating or changing biological disease-modifying antirheumatic drugs, were compared for the use of GCs at baseline. Among the GC users, the GC dose was analysed over 2 years of follow-up by group-based trajectory models. Characteristics and outcomes were compared between the trajectories.Results Among the 184 patients (RA duration 4.2 years (1.3; 12.6), Disease Activity Scores (DAS)28-C reactive protein (CRP) 4.24±2.14), 81 (44%) were on GCs. The GC users were significantly older, had higher CRP and Health Assessment Questionnaire (HAQ), more hypertension and lower lumbar T-score, but similar activity and erosive scores. Among the GC users, two trajectories were identified: trajectory 1 (n=20, 25%) with GC discontinuation in the first year and trajectory 2 (n=61, 75%) with maintenance of low-dose GCs at 2 years. Trajectory 2 was significantly associated with higher HAQ, a longer GC duration and a less frequent methotrexate association. After adjustment for HAQ, GC duration and MTX use, good EULAR responses were less frequent at 6 months and 1 year in the GC maintenance trajectory (38.3% vs 81.3%, p=0.03; 42.0% vs 82.4%, p=0.02). Diabetes, fractures and increased body mass index were noted in trajectory 2.Conclusion GCs were used in almost half of patients with established RA in real-world practice. For the majority of GC users, a long-term low dose of GCs is maintained over 2 years. These results highlight the difficulties with stopping GCs, the lack of consensus for the efficacy–safety balance of GCs, and the need to individualise the best GC tapering.

Background Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM).Objectives To assess the significance of DH/BS in patients with IM.Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1.Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p

For a better understanding of the pathophysiology of spondyloarthropathy (SpA), a detailed anatomical description of the sacroiliac joint is required because sacroiliitis is the earliest and most common sign of SpA and an essential feature for the diagnosis of ankylosing spondylitis. Beyond the anatomy, the histopathology of sacroiliac entheses and immunological mechanisms involved in sacroiliitis are crucial for a better understanding of disease causation. In this narrative review, we discuss the core anatomical, histological, and immunohistological observations involved in the development of sacroiliitis, focusing particularly on imaging-based information associated with sacroiliitis. Finally, we try to answer the question of whether at the sacroiliac joint, enthesitis precedes synovitis and subchondral bone changes in SpA.

Background Secukinumab efficacy and retention data are emerging in patients with axial spondyloarthritis (axSpA) in real-world settings. However, limited data are available on the predictive factors that affect the retention rate. The key objective was to determine whether objective signs of inflammation (OSI) were predictive of secukinumab retention at 1 year.Methods FORSYA is a French, multicentric, non-interventional, retrospective study in adult axSpA patients who received secukinumab treatment between its launch (11 August 2016) and 31 August 2018. The time to secukinumab discontinuation and retention were analysed using a Kaplan-Meier (KM) analysis. OSI was predefined by at least one of the criteria: C reactive protein ≥5 mg/L or erythrocyte sedimentation rate ≥28 mm/hour at secukinumab initiation or MRI inflammation at the sacroiliac or spine level.Results In total, 906 patients from 48 centres were included in the analysis, 42.2% of whom were men, with a mean age of 46.2±11.7 years and a mean disease duration of 9.3±9.1 years. The 1-year KM retention rate (95% CI) for secukinumab was 59% (55%–62%), whereas for patients with and without OSI, it was 58% (54%–62%) and 63% (53%–73%), respectively. In multivariate analysis, lack of prior exposure to tumour necrosis factor inhibitor (TNFi), absence of OSI and inflammatory bowel disease (IBD) were associated with a better retention of secukinumab at 1 year.Conclusion Following its approval in France, ~59% of axSpA patients retained secukinumab in daily practice, at 1 year. Prior exposure to TNFi, OSI and IBD were identified as risk factors for secukinumab discontinuation.

Objective: COVID-19 outcome may be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases (RMD) receiving immunosuppressive therapy. We aimed to investigate whether RMD patients on anti-IL6 therapy prior to SARS-CoV-2 infection have less severe disease and better outcomes of COVID-19. Methods: We conducted a retrospective national, multicentre cohort study using data from the French RMD COVID-19 cohort. We compared the severity and outcome of highly suspected or confirmed COVID-19 infection in RMD patients previously treated with tocilizumab or sarilumab (anti-IL6 group) with patients who did not receive anti-IL6 therapy (no anti-IL6 group). Results: Data were collected for 1883 patients with mean age of 55.2 years [SD 16.7] and 1256 (66.7%) female. Two hundred ten (11.1%) developed severe COVID-19 and 115 (6.4%) died. After adjusting for potential confounding factors, severe COVID-19 was less frequent in the anti-IL6 group compared with the no anti-IL6 group (aOR for moderate vs. mild severity, 0.23 [95% CI, 0.10 to 0.54], p ≤ 0.01 and aOR for severe vs. mild, 0.29 [95% CI, 0.10 to 0.81], p ≤ 0.01). No significant differences were found for the evolution of COVID-19 between the anti-IL6 group and the no anti-IL6 group (aOR for recovery with sequelae vs recovery without sequelae, 0.78 [95% CI, 0.41 to 1.48] and aOR for death vs recovery without sequelae, 0.29 [95% CI, 0.07 to 1.30]). Conclusion: RMD patients receiving anti-IL6 therapy prior to SARS-CoV-2 infection have less severe forms of COVID-19. No difference was observed in COVID-19 evolution, i.e., sequelae or death, between the groups.

Abstract Background Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels. Methods This was an international, multicentric, cross-sectional study in 2019–20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated. Results Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p

Methods to measure physical activity and sedentary behaviors typically quantify the amount of time devoted to these activities. Among patients with chronic diseases, these methods can provide interesting behavioral information, but generally do not capture detailed body motion and fine movement behaviors. Fine detection of motion may provide additional information about functional decline that is of clinical interest in chronic diseases. This perspective paper highlights the need for more developed and sophisticated tools to better identify and track the decomposition, structuration, and sequencing of the daily movements of humans. The primary goal is to provide a reliable and useful clinical diagnostic and predictive indicator of the stage and evolution of chronic diseases, in order to prevent related comorbidities and complications among patients.

There is growing interest in the alterations in body composition (BC) that accompany rheumatoid arthritis (RA). The purpose of this review is to (i) investigate how BC is currently measured in RA patients, (ii) describe alterations in body composition in RA patients and (iii) evaluate the effect on nutrition, physical training, and treatments; that is, corticosteroids and biologic Disease Modifying Anti-Rheumatic Disease (bDMARDs), on BC in RA patients. The primary-source literature for this review was acquired using PubMed, Scopus and Cochrane database searches for articles published up to March 2021. The Medical Subject Headings (MeSH) terms used were ‘Arthritis, Rheumatoid’, ‘body composition’, ‘sarcopenia’, ‘obesity’, ‘cachexia’, ‘Absorptiometry, Photon’ and ‘Electric Impedance’. The titles and abstracts of all articles were reviewed for relevant subjects. Whole-BC measurements were usually performed using dual energy x-ray absorptiometry (DXA) to quantify lean- and fat-mass parameters. In RA patients, lean mass is lower and adiposity is higher than in healthy controls, both in men and women. The prevalence of abnormal BC conditions such as overfat, sarcopenia and sarcopenic obesity is significantly higher in RA patients than in healthy controls; these alterations in BC are observed even at an early stage of the disease. Data on the effect treatments on BC in RA patients are scarce. In the few studies published, (a) creatine supplementation and progressive resistance training induce a slight and temporary increase in lean mass, (b) exposure to corticosteroids induces a gain in fat mass and (c) tumour necrosis factor alpha (TNFα) inhibitors might be associated with a gain in fat mass, while tocilizumab might be associated with a gain in lean mass. The available data clearly demonstrate that alterations in BC occur in RA patients, but data on the effect of treatments, especially bDMARDs, are inconsistent and further studies are needed in this area.

Abstract Background Coagulase-negative staphylococci (CoNS) are increasingly implicated in recent patient series of spondylodiscitis, but there are no series of CoNS-spondylodiscitis available. The objective of this study was to compare the characteristics of patients with spontaneous CoNS-spondylodiscitis with those patients with Staphylococcus aureus (SA) spondylodiscitis. Methods This was a retrospective single center study involving 147 spontaneous infectious spondylodiscitis cases observed between 2000 and 2015. The 26 cases of CoNS-spondylodiscitis (15 confirmed) were compared with 30 cases of SA-spondylodiscitis. CoNS infection was considered confirmed if the same CoNS was isolated in at least two samples at two different times. Result Patients with CoNS-spondylodiscitis were older (70 vs. 61 years of age; p = 0.01), had associated cancer more often (15% vs. 0%; p = 0.04) and had a longer diagnostic delay (>15 days in 88% vs. 60%; p = 0.01); experienced fever less often (19% vs. 50%; p = 0.01), and had lower white blood cell (7.6 vs. 9.9G/L; p = 0.01) and polymorphonuclear leucocyte counts (5.6 vs. 7.5G/L; p = 0.04). Patients with CoNS spondylodiscitis had less pronounced inflammatory syndrome (erythrocyte sedimentation rate [ESR]: 62 vs. 81 mm at 1 h; p = 0.03; CRP: 60 vs. 147 mg/L; p = 0.0003) and less common (ESR

It was shown that sodium can promote auto-immunity through the activation of the Th17 pathway. We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls.This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium excretion.Sodium excretion was greater for patients with early RA (2,849±1,350 vs. 2,182±751.7mg/day, p = 0.039) than controls. This difference remained significant after adjustment for smoking and the use of anti-hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with radiographic erosion at the time of diagnosis had a higher sodium excretion than those without (p = 0.028).Patients with early RA showed increased sodium excretion which may have contributed to autoimmunity.

The use of TNF inhibitors has been a major progress in the treatment of chronic inflammation. However, not all patients respond. In addition, response will be often lost when treatment is stopped. These clinical aspects indicate that other cytokines might be involved and we focus here on the role of IL-17. In addition, the chronic nature of joint inflammation may contribute to reduced response and enhanced chronicity. Therefore we studied the capacity of IL-17 to regulate synoviolin, an E3 ubiquitin ligase implicated in synovial hyperplasia in human rheumatoid arthritis (RA) FLS and in chronic reactivated streptococcal cell wall (SCW)-induced arthritis.Chronic reactivated SCW-induced arthritis was examined in IL-17R deficient and wild-type mice. Synoviolin expression was analysed by real-time RT-PCR, Western Blot or immunostaining in RA FLS and tissue, and p53 assessed by Western Blot. Apoptosis was detected by annexin V/propidium iodide staining, SS DNA apoptosis ELISA kit or TUNEL staining and proliferation by PCNA staining. IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17-RC) or synoviolin inhibition were achieved by small interfering RNA (siRNA) or neutralizing antibodies. IL-17 induced sustained synoviolin expression in RA FLS. Sodium nitroprusside (SNP)-induced RA FLS apoptosis was associated with reduced synoviolin expression and was rescued by IL-17 treatment with a corresponding increase in synoviolin expression. IL-17RC or IL-17RA RNA interference increased SNP-induced apoptosis, and decreased IL-17-induced synoviolin. IL-17 rescued RA FLS from apoptosis induced by synoviolin knockdown. IL-17 and TNF had additive effects on synoviolin expression and protection against apoptosis induced by synoviolin knowndown. In IL-17R deficient mice, a decrease in arthritis severity was characterized by increased synovial apoptosis, reduced proliferation and a marked reduction in synoviolin expression. A distinct absence of synoviolin expressing germinal centres in IL-17R deficient mice contrasted with synoviolin positive B cells and Th17 cells in synovial germinal centre-like structures.IL-17 induction of synoviolin may contribute at least in part to RA chronicity by prolonging the survival of RA FLS and immune cells in germinal centre reactions. These results extend the role of IL-17 to synovial hyperplasia.