Sacroiliac radiographic progression over 10 years in axSpA: data from the DESIR inception cohort.

OBJECTIVES: To evaluate sacroiliac radiographic progression over a 10-year follow-up and determine the baseline factors associated with such progression in patients with recent-onset axial spondyloarthritis (axSpA, <3 years). METHODS: This analysis was performed in the DESIR cohort (NCT01648907). The radiographic status of the patients (radiographic axSpA (r-axSpA) vs non-radiographic axSpA (nr-axSpA)) was based on the modified New York (mNY) criteria. Information on mNY criteria on the pelvic radiographs was obtained in four reading waves over a 10-year period. Images were blinded and centrally read by 3 trained readers. The % of mNY net progressors (ie, number of 'progressors' minus number of 'regressors' divided by the total number of patients) was assessed in completers (ie, pelvic radiographs at baseline and 10 years). The yearly likelihood of mNY+ was estimated using an integrated analysis (ie, including all patients with at least one available mNY score ('intention-to-follow' population) using a generalised estimating equations model and time-varying tumour necrosis factor (TNF) use as a confounder. Baseline predictors of mNY+ during 10 years were evaluated. RESULTS: Completers included 294 patients, while intention-to-follow included 659 participants. In the completers, the net % progression (from nr-axSpA to r-axSpA) was 5.8%. In the intention-to-follow population, the probability of being mNY+ was estimated to increase 0.87% (95% CI 0.56 to 1.19) per year (ie, 8.7% after 10 years) while when introducing TNF inhibitors (TNFi) as a time-varying covariate, the probability was 0.45% (95% CI 0.09 to 0.81) (ie, 4.5% after 10 years). Baseline bone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) was associated with being mNY+ over time OR 6.2 (95% CI 5.3 to 7.2) and OR 3.1 (95% CI 2.4 to 3.9) in HLA-B27+ and HLA-B27-, respectively). Male sex, symptom duration >1.5 years, Axial Spondyloarthritis Disease Activity Score ≥2.1 and smoking (only in HLA-B27 positives) were also associated with being mNY+ over 10 years. BME was not found to be a mediator of the HLA-B27 effect on mNY+ at 10 years. CONCLUSIONS: The yearly likelihood of switching from nr-axSpA to r-axSpA in patients after 10 years of follow-up was low, and even lower when considering TNFi use.

Impact of treatments on fatigue in axial spondyloarthritis: a systematic review and meta-analysis.

OBJECTIVES: Fatigue is frequent in axial spondyloarthritis (axSpA) and is difficult to improve. This systematic review aimed to assess the effects of axSpA treatment on fatigue. METHODS: A systematic review following the PRISMA recommendations was performed on PubMed, Cochrane and Embase databases. We included controlled interventional studies, cohort studies conducted in patients with axSpA meeting the ASAS 2009 criteria and measuring fatigue between 12-156 weeks of treatment. We excluded studies not written in English, case reports, abstracts, systematic reviews, meta-analysis and studies with missing data. A meta-analysis was performed for anti-TNF/anti-IL17/JAK inhibitors randomized controlled trials evaluating fatigue at week 12-16. RESULTS: 1672 studies were identified, of which 34 were selected for analysis. Twelve studies evaluated anti-TNF with a significant reduction in fatigue measured by various scores (FACIT, MFI, NRS, VAS, FSS) in 11 studies. Among the four studies evaluating anti-IL17, three showed a reduction in fatigue, with a dose effect for secukinumab. Two studies evaluated JAK inhibitors and showed a reduction in fatigue. The meta-analysis showed no differences between the DMARDs. Concerning non-pharmacological treatments, 12 of 16 studies showed a reduction in fatigue using physical activity, cryotherapy, and magnetotherapy. Two studies showed that the addition of physical activity to anti-TNF reduced fatigue more significantly. Finally, one study showed a greater efficacy in men, and two studies suggested it as in non-radiographic form. CONCLUSION: This review shows a beneficial effect of DMARD and non-pharmacological treatment on fatigue in axSpA in short and medium terms with a greater effect when combining them.

ChatGPT: when artificial intelligence replaces the rheumatologist in medical writing.

In this editorial we discuss the place of artificial intelligence (AI) in the writing of scientific articles and especially editorials. We asked chatGPT « to write an editorial for Annals of Rheumatic Diseases about how AI may replace the rheumatologist in editorial writing ¼. chatGPT's response is diplomatic and describes AI as a tool to help the rheumatologist but not replace him. AI is already used in medicine, especially in image analysis, but the domains are infinite and it is possible that AI could quickly help or replace rheumatologists in the writing of scientific articles. We discuss the ethical aspects and the future role of rheumatologists.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Impact of NSAIDs on 8-year cumulative incidence of major cardiovascular events in patients with ankylosing spondylitis: a nationwide study.

OBJECTIVES: The objectives of this study were to describe the incidence of major adverse cardiovascular events (MACEs) in French patients newly benefiting from the French Long-term Illness scheme (LTI) for AS and to evaluate the effect of various treatments on the risk of MACE occurrence. METHODS: This national cohort study was based on the French national medico-administrative database SNDS containing data on hospitalization, the LTI, and outpatient care consumption. All French patients newly receiving LTI benefits for AS from 2010 to 2013 were included. The final follow-up date was 31 December 2018. The occurrences of MACEs [stroke and myocardial infarction (MI)] and comorbidities were identified from algorithms previously described in the literature. Competitive risk analysis using propensity score and inverse weighting was performed to calculate cumulative incidence functions and to determine subhazard ratios (SHRs) for the various treatments of interest. RESULTS: Between 2010 and 2013, 22 929 patients were included [mean age 43.0 (s.d. 13.9) years, 44.9% mal]. The 8-year cumulative incidences of MACE, stroke, and MI were 1.81% (1.61-2.05), 0.97% (0.83-1.14), and 0.85% (0.71-1.04), respectively. NSAIDs [SHR: 0.39 (0.32-0.50), P < 0.001] and anti-TNF [SHR 0.61 (0.46-0.80), P < 0.001], but not anti-IL17 [2.10 (0.79-5.57)] were associated with a lower risk of MACE occurrence. CONCLUSION: MACE incidence rates at 8 years are low in patients newly benefiting from LTI for AS. Our results support the hypothesis of a protective role of NSAIDs and anti-TNF in cardiovascular risk in these patients.

Characteristics of patients with difficult-to-treat rheumatoid arthritis in a French single-centre hospital.

OBJECTIVES: To compare the features of difficult-to-treat rheumatoid arthritis (D2TRA) patients using two different definitions according to the previous failure of targeted therapies. METHODS: We stratified consecutive RA patients treated at Cochin Hospital into two groups, a D2TRA group and a non-D2TRA group, according to two definitions of D2TRA. Both definitions defined D2TRA as RAs failing at least two targeted therapies, with a different mechanism of action for the EULAR-D2TRA definition or without prejudging the mechanism of action and for the Alternative D2TRA definition. RESULTS: We included 320 consecutive RA patients. We identified 76 EULAR-D2TRA and 244 non-DTRA patients, and 120 Alternative D2TRA and 200 non-DTRA patients. Compared with non-D2TRA, D2TRA patients from both definitions were more likely to have lower socioeconomic level, positive rheumatoid factor, interstitial lung disease, higher DAS28-CRP and were more likely to respond to rituximab and Janus kinase inhibitors. Although EULAR and Alternative D2TRA patients displayed similar clinical and biological features, they were characterized by different therapeutic profiles. We observed fewer patients receiving methotrexate in the Alternative D2TRA group (53% vs 64%, P = 0.046). Patients with Alternative D2TRA not fulfilling the EULAR definition (n = 44) had all received two successive first-line TNF inhibitors, a monoclonal antibody and a soluble receptor, and were comparable to EULAR-D2TRA patients with regards to all other characteristics. CONCLUSION: Low socioeconomic status, diabetes, interstitial lung disease and absence of combination with methotrexate allow identification of D2TRA. In addition, the inclusion as 'early-D2TRA' of patients failing two TNF inhibitors in the EULAR definition of D2TRA would facilitate the rapid identification of D2TRA patients.

Efficacy and management of tocilizumab in polymyalgia rheumatica: results of a multicenter retrospective observational study.

OBJECTIVES: The efficacy of anti-IL6 receptors such as Tocilizumab (TCZ) was demonstrated in patients with Polymyalgia Rheumatica (PMR) in two recent randomized controlled trials. The objective of this multicentre retrospective study was to assess the efficacy of TCZ in PMR patients requiring GC-sparing treatment, as well as different strategies for TCZ withdrawal. METHODS: We conducted a multicentre study in French tertiary health care departments for patients with PMR. PMR patients receiving off-label TCZ between 2015 and 2022 were included. The primary end point was the proportion of patients tapering to glucocorticoids (GCs) ≤5mg/day 6 months after the first TCZ infusion. The secondary endpoints were the proportion in whom GC was discontinued during follow-up, and the proportion of patients in whom TCZ was discontinued. RESULTS: Fifty-three PMR patients were included. Thirty-one (31) patients suffered from active PMR despite csDMARDs. GCs were ≤5mg/day in 77% of the patients (95% confidence interval [CI95%]: 36-89) at 6 months, and in 97% of the patients at 12 months. Six and 12 months after the first TCZ infusion, the proportions of GC-free patients were 22.5% (CI95%: 12.7-37.8) and 58.3% (CI95%: 43.2-74.1), respectively. Among TCZ withdrawal strategies, TCZ infusion spacing and TCZ dose reduction were more successful (success in 87% and 79% of attempts, respectively) than TCZ discontinuation (success in 52% of attempts; p= 0.012 and p= 0.039, respectively). CONCLUSION: In GC-dependent PMR patients, treatment with TCZ led to a drastic decrease in GC dose and remission of PMR. TCZ dose reduction or TCZ infusion spacing are good options to consider in TCZ withdrawal.

Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

Exploring remission concept in axial spondyloarthritis through the perception of rheumatologists using vignettes and priority ratings.

OBJECTIVES: The optimal treatment target in axial spondyloarthritis (axSpA) is remission; however, a consensual definition of remission is lacking. Our objective was to explore rheumatologists' perception of remission using vignette cases and a priority exercise. METHODS: A cross-sectional survey of rheumatologists' perceptions of remission in axSpA was performed in 2020 using (i) 36 vignette cases, with a single clinical picture and three varying parameters [axial pain (ranging from 2 to 5 on a 0-10 scale)], fatigue (2-8), and morning stiffness (<15 min, 30 min or 1 h), assessed as remission yes/no; and (ii) prioritization of elements to consider for remission from a list of 12 items: BASDAI, ASDAS, elements of BASDAI and ASDAS including CRP, NSAID use, extra-articular manifestations (EAMs), and other explanations of symptoms, e.g. fibromyalgia. Analyses were descriptive. RESULTS: Overall, 200 French rheumatologists participated in 2400 vignette evaluations. Of these, 463 (19%) were classified as remission. The six vignette cases representing 56% of all remission cases had <15 min duration of morning stiffness and axial pain ≤3/10, regardless of fatigue levels. Prioritized items for remission were: morning stiffness (75%), EAMs (75%), NSAID use (71%), axial pain (68%) and CRP (66%). CONCLUSIONS: When conceptualizing remission in axSpA, rheumatologists took into account morning stiffness and axial pain as expected; the link between remission and fatigue was much weaker. Furthermore, rheumatologists also included EAMs and NSAID use in the concept of remission. Consensus is needed for definition of remission in axSpA.

Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept.

OBJECTIVE: To compare the risk of diverticulitis and gastrointestinal perforation (GIP) in RA treated with tocilizumab (TCZ) compared with rituximab (RTX) and abatacept (ABA). METHODS: We conducted a population-based study using three observational French registries on TCZ, RTX and ABA in RA. Using a propensity score approach, we compared the risk of diverticulitis or GIP in these patients. RESULTS: With inverse probability weighting, there was an increased risk of diverticulitis in TCZ-treated patients compared with RTX- or ABA-treated patients [hazard ratio (HR)=3.1 (95% CI: 1.5, 6.3), P =0.002]. Moreover, patients treated with TCZ had also an increased risk of GIP due to diverticulitis compared with those treated with RTX or ABA [HR=3.8 (1.1-13.6), P =0.04], resulting in an overall increased risk of GIP [HR=2.9 (1.1-7.8), P =0.03], while no significant increased risk of GIP due to any other aetiology was found in TCZ treated patients. Diverticulitis and GIP occurred earlier with TCZ than other drugs after the last perfusion (P =0.01), with atypical clinical presentation (slow transit in 30%, P =0.04) and lower acute-phase reactants at the time of the event (P =0.005). CONCLUSION: TCZ for RA was associated with increased odds of diverticulitis as well as GIP due to diverticulitis as compared with RTX and ABA. Our study confirms the increased odds of GIP in patients receiving TCZ, which might be explained by an increased risk of diverticulitis with misleading clinical presentation.

Factors associated with remission at 5-year follow-up in recent-onset axial spondyloarthritis: results from the DESIR cohort.

OBJECTIVE: The factors contributing to long-term remission in axial SpA (axSpA) are unclear. We aimed to characterize individuals with axSpA at the 5-year follow-up to identify baseline factors associated with remission. METHODS: We included all patients from the DESIR cohort (with recent-onset axSpA) with an available Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP < 1.3) were compared with those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on TNF inhibitor (TNFi) exposure was used. RESULTS: Overall, 111/449 patients (25%) were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared with 17% (34/202) of those exposed to TNFi. Patients in remission after 5 years were more likely to be male, HLA-B27+, have a lower BMI, and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi included lower BASDAI [adjusted odds ratio (ORa) 0.9, 95% CI: 0.8, 0.9) and history of peripheral arthritis (ORa 2.1, 95% CI: 1.2, 5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95% CI: 1.6, 5.1), lower enthesitis index (ORa 0.8, 95% CI: 0.7, 0.9), lower BASDAI (ORa 0.9, 95% CI: 0.9, 0.9) and lower BMI (ORa 0.8, 95% CI: 0.7, 0.9). CONCLUSION: This study highlights the difficulty in achieving 5-year remission in those with recent-onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial.

OBJECTIVE: To evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis. METHODS: This was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0-100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients' and physicians' global assessment and function scores. RESULTS: Of 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was -7.9 (SD 19.4) and -9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group. CONCLUSION: Tocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

Visceral adiposity in patients with psoriatic arthritis and psoriasis alone and its relationship with metabolic and cardiovascular risk.

BACKGROUND: Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO). METHODS: Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin, leptin, resistin and retinol-binding protein-4 (RBP4)] were measured. RESULTS: Data for 52 patients with PsA and 52 patients with PsO and their respective paired controls were analysed. Android fat and visceral fat were found to be significantly higher in patients with PsO compared with their controls, while these measurements did not differ between patients with PsA and their controls. By multivariate analysis, after adjusting for age, sex and BMI, visceral fat was higher in PsO patients compared with PsA patients (P = 0.0004) and the whole group of controls (P = 0.0013). Insulin levels and HOMA-IR were increased in both PsA and PsO groups. High-molecular-weight/total adiponectin ratio was decreased in patients with PsO. RBP4 was significantly higher in both PsA and PsO patients. In patients with PsO, visceral fat strongly correlated with SCORE (r = 0.61). CONCLUSION: Visceral fat accumulates more in PsO alone than in PsA. Visceral adiposity may be a more pressing concern in PsO relative to PsA. TRIAL REGISTRATION: The ADIPSO study (Évaluation du tissu ADIpeux et des adipokines dans le PSOriasis et le rhumatisme psoriasique et analyse de ses relations avec le risque cardiovasculaire) is a case-control study conducted in Besançon, France, and is registered on ClinicalTrials.gov under the number NCT02849795.

Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA).

OBJECTIVE: To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). RESULTS: A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). CONCLUSION: This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.

Animal models to study pathogenesis and treatments of cardiac disorders in rheumatoid arthritis: Advances and challenges for clinical translation.

Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.

Reactive Arthritis: Treatment Challenges and Future Perspectives.

PURPOSE OF THE REVIEW: Reactive arthritis is synovitis related to an infection away from the joint. The evolution is variable, frequently self-limited, but with the possible evolution to a prolonged form, generating functional incapacity and sequelae. RECENT FINDINGS: New microbiological families have been incriminated and pathophysiological links have been clarified, highlighting the role of the mucous membranes (gut in particular), specific cell populations, and the production of pro-inflammatory cytokines. First-line pharmacological treatment is based on NSAIDs. In case of failure, synthetic and more recently biological DMARDs are indicated. Only open data are available for biological DMARDs but suggest good efficacy and safety. Reactive arthritis has not disappeared. The diagnosis must be mentioned by the clinic and history to allow the rapid introduction of an appropriate treatment.

A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16-0.61), p = 0.001). No association was found with any of the other SNPs tested.

Structural efficacy of NSAIDs, COX-2 inhibitor and glucocorticoid compared with TNFα blocker: a study in adjuvant-induced arthritis rats.

OBJECTIVE: To evaluate radiographic outcomes after an early treatment for 21 days with etanercept, naproxen, celecoxib, prednisone or methotrexate in adjuvant-induced arthritis in rats. METHODS: At the onset of arthritis, rats were daily treated with naproxen (10 mg/kg/day i.p.), celecoxib (3 mg/kg/day), prednisolone (10 mg/kg/day), etanercept (10 mg/kg/3 days), methotrexate (2 mg/kg/3 days) or saline solution (vehicle) for 21 days. The arthritis score was daily monitored. At the end of treatment, a hind paw radiographic examination was performed with a BMA high-resolution digital X-ray system (40 mV, 10 mA). A score of 0-20 was determined for each paw. Plasma levels of TNFα were measured. RESULTS: Compared with vehicle, all treatments reduced (P < 0.001) the arthritis score. All treatments, except methotrexate, slowed radiographic destruction (P < 0.001). All treatments, except etanercept, reduced the plasma level of TNFα. Naproxen, glucocorticoid and celecoxib were more effective than etanercept on the radiographic score (P < 0.01). Naproxen was the only treatment to be more effective on all different radiographic subscores than etanercept. CONCLUSION: Our study demonstrated for the first time that an early treatment with NSAIDs, excluding cyclooxygenase-2 selective inhibitor, is more beneficial than a TNFα blocker in preventing structural damage in adjuvant-induced arthritis.