RMD Open

Objectives To assess the effects of 24 weeks active treatment with baricitinib, a JAK1/2 inhibitor, in adult idiopathic inflammatory myopathy (IIM). Methods Patients with active dermatomyositis (DM) or polymyositis (PM) were enrolled into a 1:1 randomized treatment delayed-start design clinical trial (NCT04208464). Participants received 24 weeks baricitinib plus 12 weeks follow-up (Immediate-start), or 12 weeks standard of care plus 24 weeks baricitinib (Delayed-start). The primary outcome was clinical response after 24 weeks active treatment, defined as minimal improvement (Total Improvement Score >20 [TIS20]). Secondary outcomes included: TIS40 (moderate), TIS60 (major) response, between-arm comparison, time to achieve response, change in clinical outcome measures. steroid-sparing and cumulative adverse events. Results 14/15 (93%) randomized participants (mean age 43.2 years [11.6 SD]; 13 DM, 2 PM; 11 female) completed the study (baseline to 36 weeks) and all achieved TIS20 at 24 weeks post-active treatment (95% exact CI 0.68-1.00). 9/15 (60%) achieved TIS40 response and 2/15 (13%) TIS60 response. At 12 weeks post-randomization, 11/15 (73%) patients achieved at least TIS20 (95%CI 0.45-0.92), including all Immediate-start arm patients and four Delayed-start arm patients. At the same time point, evidence of a difference was noted for patient global, extramuscular, CDASI skin activity, pain, fatigue and SF-36 mental/physical health scores. Two hospitalisation serious adverse events were documented, neither related to study drug. Conclusions Treatment of IIM with baricitinib resulted in improved clinical outcome after 24 weeks. Significant improvement after 12 weeks treatment was also evident. No significant safety concerns were raised. A randomized placebo-controlled trial is needed to confirm the efficacy in patients with IIM.

BackgroundObesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). Among obese patients, abatacept was suggested as a preferable option to tumour necrosis factor alpha (TNF) inhibitors. Sex and gender differences in RA were described. ObjectivesTo assess the comparative effectiveness of etanercept, infliximab, and abatacept, compared to adalimumab, in patients with RA stratified by body mass index (BMI) and sex. MethodsObservational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). RA patients were classified in BMI-based cohorts: obese, overweight, and normal weight. Each BMI cohort was studied overall and stratified by sex. The study outcome was remission within 12-months, defined as a disease activity score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction (CARRAC). Logistic regression compared the effectiveness of etanercept, infliximab, and abatacept versus adalimumab. ResultsThe study included 443 obese, 829 overweight, and 1243 normal weight RA patients. Across the BMI cohorts, there were no significant differences in the odds of remission at [&le;]12-months for the study drugs compared to adalimumab. However, among females, an inverse effect for infliximab was found, whereby overweight patients had higher odds of remission, while obese patients had lower odds of remission, compared to the respective adalimumab users. ConclusionsDespite the previous hypothesis, treatment with abatacept showed similar odds of remission compared to adalimumab in all BMI cohorts. Conversely, compared to adalimumab, infliximab performed better in overweight female patients but worse in female patients with obesity. However, further validation is needed.

This study assessed the evidence on the efficacy of tapering anti-TNF, JAK inhibitors, and tocilizumab in rheumatoid arthritis patients. In February 2024, a systematic review was conducted by searching Medline, Embase, Web of Sciences, and the Cochrane Library for randomized controlled trials comparing the efficacy of tapering vs standard treatment. The outcomes evaluated were the maintenance of low disease activity (LDA), remission, and flare-ups. A meta-analysis was conducted when data were available. The risk of bias was assessed using RoB 2. The study was registered on PROSPERO. A total of 2861 records were identified, with 1638 records screened after removing duplicates. Finally, fifteen studies involving 2782 patients were included. Follow-up ranged from 6 months to 3.5 years. Tapering anti-TNF did not affect LDA maintenance while showing a lower probability of maintaining remission (RR 0.69, 95% CI 0.57-0.84) and a higher risk of flare-ups (RR 1.96, 95% CI 1.57-2.45). Tapering JAK inhibitors showed a decreased probability of maintaining LDA (RR 0.83, 95% CI 0.76-0.91) and remission (RR 0.86, 95% CI 0.75-0.99), and more frequent and earlier flares. Tapering tocilizumab also resulted in a lower probability of maintaining LDA or remission and a higher risk of flares. Although tapering anti-TNF did not affect LDA maintenance, due to the increased risk of flare-ups and reduced remission probability, routine dose tapering of anti-TNF, JAK inhibitors, and tocilizumab for all patients is not recommended. Identifying patients who may benefit from tapering is crucial.

ObjectivesTo evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response, and efficacy of E6742 in a phase 1/2 study in patients with systemic lupus erythematosus (SLE). MethodsTwo sequential cohorts of SLE patients were enrolled and randomized to 12 weeks of twice-daily treatment with E6742 (100 or 200 mg; n = 8 or 9) or placebo (n = 9). ResultsThe proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% for 100 mg; 77.8% for 200 mg) and 66.7% in the placebo group. No Common Terminology Criteria for Adverse Events [&ge;] Grade 3 TEAEs occurred. PK parameter levels were similar between SLE patients and healthy adults in previous phase 1 studies. The interferon gene signature (IGS) and levels of proinflammatory cytokines (interleukin-1{beta}, interleukin-6, tumor necrosis factor-) after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. Dose-dependent improvements in the British Isles Lupus Assessment Group-based Composite Lupus Assessment response were observed at Week 12 in the E6742 (37.5% for 100 mg; 57.1% for 200 mg) and placebo (33.3%) groups. E6742 also had therapeutic effects on other symptoms, including skin inflammation, arthritis, and levels of anti-double-stranded DNA antibodies and complements. ConclusionsE6742 had a favorable safety profile and was well tolerated, with marked IGS responses and sufficient efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials. Trial registration numberNCT05278663. KEY MESSAGESWhat is already known on this topic O_LIBecause of the limited efficacy and safety concerns of current drug therapies, unmet medical needs remain for many patients with systemic lupus erythematosus (SLE), necessitating new, more efficacious drugs. C_LIO_LIThere is strong evidence for the relationship between Toll-like receptor (TLR)7/8 and SLE pathophysiology, and two phase 1 clinical studies of E6742, a small molecular selective dual antagonist of TLR7/8, in healthy adults showed good tolerance without safety issues. C_LI What this study adds O_LIE6742 was well tolerated in this phase 1/2 clinical trial of patients with SLE, demonstrating a favorable safety profile and providing a markedly improved interferon gene signature and sufficient efficacy signals. C_LI How this study might affect research, practice or policy O_LIThis study provides the first clinical evidence to suggest that E6742, as a first-in-class TLR7/8 inhibitor, may be beneficial for SLE. C_LIO_LIThe study outcomes also support larger, longer-term clinical trials of E6742. C_LI

ObjectiveMinor salivary gland biopsy (MSGB) is a standard procedure in the diagnosis of Sjogrens disease (SjD). Biopsy techniques using a vertical or horizontal mucosal incision are applied in daily practice; the former may be safer due to underlying neuroanatomy. Here we aim to quantify and classify adverse events (AEs) of MSGB using vertical incision technique. Patients and MethodsMedical records of patients with suspected SjD who underwent MSGB at our outpatient clinic between January 2014 and April 2024 and had follow-up visits were analyzed. The MSBG consisted of a 1 cm linear vertical incision in the oral mucosa of the lower lip to collect up to five lip salivary glands. Results202 of 257 patients undergoing MSGB met inclusion criteria. Median follow-up time was 16.5 (0.5-124.0) months. Four biopsies (2%) did not yield sufficient material for histological analysis. One serious adverse event (0.5%), local persistent paresthesia, and two moderate adverse events (1.0%), including one case of prolonged bleeding and one unclassified event, were reported. Mild AEs occurred in 18 patients (8.9%). Local discomfort after biopsy affected 32 patients (15.8%). AEs subsided either during or up to 2 hours after biopsy in 14 patients (6.9%) and in 38 patients (18.8%) within three weeks, respectively. ConclusionsMSGB with vertical incision technique has a very low frequency of serious and long-term complications with a success rate of 98%. Significance and InnovationsO_LIMinor salivary gland biopsy with lateral vertical incision technique has a success rate of 98%. C_LIO_LISerious complications occurred less frequent than previously reported for horizontal incision technique. C_LI

ObjectivesTo assess whether baseline ESR-CRP difference (D score) is associated with discontinuation due to loss of efficacy during Janus kinase inhibitor therapy after biologic failure in rheumatoid arthritis. MethodsSingle-centre retrospective cohort of 24 patients with rheumatoid arthritis who initiated a Janus kinase inhibitor after inadequate response to at least one biologic DMARD. D score was ESR (mm/h) minus CRP (mg/L). The primary outcome was discontinuation due to loss of efficacy; other discontinuations were censored. Kaplan-Meier curves and Cox models were used. ResultsSeven patients discontinued due to loss of efficacy. After dichotomisation at the median D score (20.3; n = 12 per group), 1-year LOE-free persistence was 90.9% in the high D group and 43.2% in the low D group (log-rank p = 0.004). The hazard ratio per 10-unit increase was 0.47 (95% CI 0.29 to 0.76; p = 0.002) and 0.41 after age adjustment (0.22 to 0.74; p = 0.003). ConclusionsBaseline D score was associated with lower risk of discontinuation due to loss of efficacy. Larger studies are needed. Key messagesO_LILoss-of-efficacy discontinuation tended to cluster in patients with low ESR and low CRP at baseline. C_LIO_LIHigher baseline D score was associated with fewer loss-of-efficacy discontinuations during JAK inhibitor therapy. C_LIO_LID score from ESR and CRP may complement post-biologic treatment decisions, pending external validation. C_LI

ObjectiveTo assess the comparative efficacy and safety of approved biologic disease-modifying antirheumatic drugs (bDMARDs), biosimilars, and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) for patients with rheumatoid arthritis (RA) who had inadequate responses to methotrexate (MTX). Results53 eligible studies were identified and 44 studies were included in a network meta-analysis. Using Surface Under the Cumulative Ranking Curve (SUCRA), tofacitinib (10 mg bid) with MTX [Relative risk (RR) 95% confidence interval (CI) 4.65 (2.98-7.27)] and tofacitinib (10 mg bid) [RR (95%CI)1.96 (1.27-3.03)] were ranked highest among tsDMARDs for increasing remission rate at 24-26 weeks and 48-52 weeks, respectively. For bDMARDs, tocilizumab (8 mg/kg) with MTX was ranked with highest treatment effect for remission at both 24-26 and 48-52 weeks [RR (95%CI) 3.06 (2.27-4.12); RR (95%CI) 2.52 (1.94-3.28)]. For safety, baricitinib (4 mg) and tofacitinib (5 mg bid) with MTX likely showed an increased risk of HZ with statistical significance [for baricitinib, RR (95%CI) 3.52 (1.38-9.02) at 24-26 weeks, and RR (95%CI) 4.20 (1.22-14.48) at 48-52 weeks, and for tofacitinib, RR (95%CI) 5.38 (1.00-28.91) at 48-52 weeks]. No statistically significant safety concerns for serious infection, tuberculosis (TB), cancer, and cardiovascular (CV) events were identified. ConclusionsFor RA patients who failed MTX, bDMARDs, biosimilars, and tsDMARDs monotherapy and combination therapy with MTX provided better treatment outcomes than MTX monotherapy with modest safety concerns within 24-52 weeks. A scarcity of longer-term effects and post-market surveillance necessitates further analyses using long-term patient-level data to improve the medication profile. Rheumatology key messagesO_LIFor RA patients who failed MTX and other conventional DMARDs, different types of DMARDs are available. C_LIO_LIAt dose- and time point-specific levels, tofacitinib (10 mg bd) showed the highest probability to be the most effective in achieving remission at 24-26 weeks. C_LIO_LIAn increased risk of herpes zoster was found for baricitinib (4 mg) and tofacitinib (5 mg bid) with MTX. C_LI

BackgroundGiant cell arteritis (GCA) is a type of large vessel vasculitis that causes inflammation, scarring and stenosis in large vessels. Clinical symptoms include headaches, visual changes and myalgias. The standard treatment for GCA consists of glucocorticoid therapy, however long-term use of glucocorticoid therapy poses important health risks. For this reason, there has been a growing interest in exploring other glucocorticoid-sparing therapies, such as leflunomide. The objective of this systematic review is to assess the efficacy and safety of leflunomide in the treatment of GCA. MethodsWe will include studies with adult patients who received leflunomide in the treatment of GCA. We will include randomized controlled trials, cohort studies, case-control studies, and case series. The intervention of interest is the use of leflunomide, which may be initiated at any time over the course of the disease. The comparator is glucocorticoid therapy alone. The primary efficacy outcome is the incidence (proportion) of patients who attain GC-free remission, as defined by the following: 1) absence of signs or symptoms of GCA, and/or 2) normalization of inflammatory markers, and/or 3) radiologic response, and 4) complete discontinuation of GC. Outcomes will be assessed after 1 year of follow-up. Quality appraisal will be performed using the respective risk of bias tools. We will perform a meta-analysis using a random-effects model if the included studies are sufficiently homogenous. For quantitative synthesis, we will employ Cochran-Mantel-Haenszel method with odds ratios as a measure of effect and 95% confidence intervals for our primary endpoint. DiscussionThe challenge in the treatment of GCA is attaining and maintaining disease remission with the least amount of glucocorticoid therapy possible. The only approved glucocorticoid-sparing agent in the treatment of large vessel vasculitis is tocilizumab. Leflunomide is a molecule with similar downstream effects on dendritic cells and cytokines as tocilizumab. Should leflunomide demonstrate similar benefits, it would be a cost-effective, safe, and user-friendly (oral route) option. Systematic review registrationOur systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42023490373).

Backgroundrheumatologists recognize the importance of rehabilitation in patients with rheumatoid arthritis (RA), but they are not confident if patients with significant disease activity would benefit from it. ObjectiveTo verify if rheumatoid arthritis patients with moderate to severe inflammatory activity (MHA) improve functional capacity (FC) after a comprehensive rehabilitation program. MethodsNested case-control study. RA patients who completed a rehabilitation program between June 2014 and December 2017 were included. The interventions were prescribed according to the rehabilitation teams discretion. FC was assessed with Health Assessment Questionnaire Disability Index (HAQ) and compared between before and after interventions. The group which improved at least 50% in CDAI was compared to the group which achieved <50%. ResultsWe included 46 patients with complete HAQ and baseline CDAI data, with a mean age of 53.6 years and mean disease duration of 11.8 years. HAQ and CDAI improved on average 0.481 ({+/-} 0.500) and 14.2 ({+/-} 16.7), respectively. Patients who improved CDAI tended to have a greater mean HAQ difference (0.6 vs. 0.3; p = 0.058). Conversely, patients who did not improve disease activity had a HAQ reduction of 0.3 ({+/-} 0.4). Post-hoc analysis was performed on the group of 9 patients with baseline CDAI [&le;]10. A mean baseline CDAI of 5.2 and a mean HAQ difference of 0.319 (0.079; 0.56; p = 0.016) were found. ConclusionsAfter rehabilitation, RA patients with sustained MHA improved FC similarly to patients with baseline mild activity or remission. Thus, patients with RA and MHA may benefit from rehabilitation concurrently with drug treatment. This study suggests that the range of improvement in FC with rehabilitation appears to have an additive effect to the drug therapy.

BackgroundDisease-modifying therapies (DMTs) have become the mainstay of treatment for relapsing forms of multiple sclerosis (MS), reducing relapse rates and slowing disease progression. ObjectivesTo determine whether or not available MS DMTs have demonstrated an increase in safety, efficacy, and tolerability over time. MethodsResults from pivotal phase III trials of approved MS DMTs were used to create a dataset of relevant outcomes. Common endpoints analyzed include annualized relapse rates (ARR), rates of serious adverse events (SAE), and rates of discontinuation due to adverse events. Trial comparator, active or placebo, was also documented. Descriptive statistics and Fisher exact tests were performed on outcomes stratified by recency of pivotal trials. ResultsOn visual inspection, there was a trend of decrease in ARR. A significant relationship was seen between recent approvals and trial design with an active comparator (p=0.004), as well as between recent approvals and ARR (p=0.020). No significance was found between recent approvals and SAE (p=0.138), formulation and discontinuation (p=0.559), or recent approvals and formulation (p=0.352). ConclusionDMTs for relapsing forms of MS increased in efficacy over time. Oral therapies offered similar tolerability to other routes of administration. Further research is warranted to identify if these clinical trial findings translate to real world evidence. What was already knownO_LIThe number of FDA approved disease-modifying therapies for multiple sclerosis has been steadily increasing. Available routes of administration include injectable, oral, and infusions. C_LIO_LIThese medications are proven to be effective in reducing MS relapse rates and slowing overall disease progression, with varying degrees of safety and tolerability. C_LIO_LIThe comparative efficacy of these therapies varies, with certain medications often deemed high efficacy. C_LI What this study addsO_LIWe used published phase III trial results for each medication to provide a direct comparison between each medications efficacy, safety, and tolerability at time of approval. C_LIO_LIOur analysis demonstrates a trend in increasing efficacy of available therapies along with the use of active comparators for controls in disease modifying treatments for multiple sclerosis. C_LI

Background The phase 3 ADVOCATE trial evaluated the efficacy and safety of avacopan in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Concerns raised regarding the 2019 primary endpoint adjudication process prompted a blinded, independent readjudication of all participants' primary outcomes, the results of which are described here. Methods Patients with GPA or MPA were randomized 1:1 to receive oral avacopan 30 mg twice daily or oral prednisone on a scheduled taper, each in combination with rituximab- or cyclophosphamide-based standard of care. In 2026, the Duke Clinical Research Institute Clinical Events Classification group conducted an independent, blinded committee re-adjudicated the Birmingham Vasculitis Activity Score (BVAS), relapse, and remission from weeks 26 through 52 using procedures aligned with the original adjudication charter. The primary endpoints were remission at week 26 and sustained remission at week 52. As per the original analysis plan, noninferiority and superiority were declared if the lower bounds of the 95% confidence interval (CI) for the difference in the primary outcome rates between avacopan and a prednisone taper were greater than -20.0 and 0.0 percentage points, respectively. Results Among 330 participants in the intent-to-treat population, remission at week 26 was achieved by 68.1% (113/166) and 67.1% (110/164) of participants in the avacopan and prednisone taper groups, respectively, in the 2026 readjudication (adjusted difference: 2.2%; 95% CI, -7.5, 11.9), compared with 72.3% (120/166) and 70.1% (115/164) in the 2019 primary outcome adjudication (adjusted difference: 3.4%; 95% CI, -6.0, 12.8). Sustained remission at week 52 was achieved by 61.4% (102/166) and 52.4% (86/164) of participants, respectively, in the 2026 readjudication (adjusted difference: 9.8%; 95% CI, -0.3, 19.9), compared with 65.7% (109/166) and 54.9% (90/164) in the 2019 readjudication (adjusted difference: 12.5%; 95% CI, 2.6, 22.3). Concordance between the 2019 and 2026 adjudications was 95.2% for remission and 93.6% for sustained remission. Conclusion The re-analysis of ADVOCATE based on the 2026 readjudication further supports the efficacy of avacopan for GPA/MPA. Non-inferiority of avacopan versus a prednisone taper was confirmed at weeks 26 and 52 despite a median 81% reduction in glucocorticoid exposure observed in the avacopan versus prednisone taper groups. While a consistent numerical difference favoring avacopan at week 52 was observed in the 2019 and 2026 analyses, this difference did not reach statistical superiority.

Background. Tocilizumab (TCZ), a monoclonal antibody directed against the interleukin-6 receptor, is used in rheumatoid arthritis (RA) after inadequate response or secondary loss of response to conventional synthetic and biological disease-modifying antirheumatic drugs (DMARDs). Real-world data from North African cohorts remain scarce. We assessed the effectiveness and safety of TCZ in routine care and explored baseline factors associated with 6-month outcomes. Methods. We conducted a retrospective, single-centre cohort study of 44 consecutive patients with RA treated with TCZ between April 2019 and January 2024 in the Department of Rheumatology, Moulay Ismail Hospital, Meknes, Morocco. Demographic, clinical, laboratory, treatment and follow-up data were extracted from medical records using a standardised electronic form. The primary effectiveness outcome was the European Alliance of Associations for Rheumatology (EULAR) response at 6 months; DAS28-ESR remission was defined as DAS28-ESR below 2.6. Safety outcomes comprised infections, neutropenia, liver-enzyme abnormalities and lipid abnormalities. Longitudinal changes were compared with the Wilcoxon signed-rank test, and associations between baseline variables dichotomised at their median and 6-month outcomes were examined with chi-square tests, in SPSS version 29. Results. The cohort comprised 33 women (75.0%), with a median age of 57 years (range 32-82) and a mean RA duration of 12.97+/-9.1 years. Patients had received a mean of 2.5+/-1.8 previous conventional DMARDs, and 41 (93.2%) had received at least one previous biological agent, including two or more tumour necrosis factor (TNF) inhibitors in 36 (81.8%). At 6 months, outcome data were available for 34 patients: 23 (67.6%) achieved a good EULAR response, 6 (17.6%) a moderate response and 5 (14.7%) no response; 12 (35.3%) were in DAS28-ESR remission. Mean DAS28-ESR fell from 5.10+/-1.18 at baseline to 2.74+/-1.38 at 6 months and 2.45+/-1.33 at 12 months, and the mean prednisone-equivalent dose fell from 8.3+/-7.1 to 5 mg/day. Twenty-two infectious episodes were recorded, including one serious infection (purulent pleurisy) requiring hospitalisation; 5 patients (11.4%) had a temporary interruption and 1 (2.3%) a permanent discontinuation for hepatic cytolysis. A neutrophil count below 1,500/mm3 occurred in 13 patients (29.5%), with no count below 1,000/mm3, while mean neutrophils declined from 6.3+/-3.0 to 2.6+/-1.2 G/L at 12 months. Mean LDL cholesterol rose from 1.18 to 1.49 g/L and HDL cholesterol from 0.58 to 0.82 g/L. Rheumatoid-factor positivity was the only baseline variable associated with the EULAR response category (p=0.007); a baseline tender joint count above six was associated with a lower remission rate (23.5%, p=0.007), as was, borderline, a pain visual analogue scale above 65 mm (31.2%, p=0.05). Conclusions. In this heavily pretreated real-world RA cohort, TCZ was associated with a substantial and sustained reduction in disease activity and a manageable safety profile consistent with its known signals. A high baseline articular and pain burden was associated with a lower probability of remission. The small sample, incomplete 6-month follow-up, retrospective design and absence of adjusted effect estimates limit interpretation, and the reported associations should be regarded as hypothesis-generating.

ObjectivesThe individual and socioeconomic burden of sarcopenia in rheumatoid arthritis (RA) is most relevant. However, longitudinal cohort data are scarce. MethodsProspective, single-center, controlled, observational cohort study of consecutive 124 postmenopausal women, 53 with RA, 71 healthy controls (HC). Low muscle mass and low muscle strengths was defined according to the European working group on sarcopenia in older people 2019 (appendicular lean mass index [ALMI] via dual-energy x-ray absorptiometry < 5.5 Kg/m2; handgrip strength via dynamometer < 16 Kg). Linear regression models were calculated including demographic and anthropometric data, comorbidities, and co-medication as confounders. ResultsMedian age was 63 (IQR 56, 70), follow-up 2.1 (IQR 2.0, 5.3) years. At baseline, median ALMI was 6.2 (IQR 6.0, 6.5) Kg/m2 in RA patients, 6.3 (IQR 5.6, 6.9) Kg/m2 in HC (p = 0.64) with no difference in rates of low muscle mass (RA 16.2 % vs. HC 15.1 %). In the fully adjusted model, mean change in ALMI per year was -0.05 (95%CI -0.10 to -0.01) Kg/m2 in RA patients and 0.00 (95%CI -0.02 to 0.03) Kg/m2 in HC resulting in a differential loss of -0.06 (95%CI -0.11 to -0.01) Kg/m2 per year (p = 0.027). For RA patients, the adjusted OR of experiencing any loss of muscle mass was 3.98 (95%CI 1.47 to 10.77) compared to HC (p = 0.007). On average, RA patients lost 0.78 % of muscle mass per year. At baseline, low grip strength was seen in 27.3 % of RA patients and in 2.9 % of HC (p = 0.002). In both groups, grip strength did not decline during study period. TNF inhibitors were associated with less, T-cell inhibition with greater loss of muscle mass. Low mass at baseline, disease duration and disease activity were not associated with loss of muscle mass. ConclusionPostmenopausal women with RA have a significant risk of accelerated loss of muscle mass over time.

ObjectiveThe Broccoli in Osteoarthritis (BRIO Study) was conducted to determine whether dietary sulforaphane (SFN), consumed as broccoli, improves pain and/or physical function in participants with knee osteoarthritis (OA). This was a proof of principle study to test the feasibility of the trial to optimise the design of an appropriately powered study. DesignTwo-centre, double-blind, two-arm parallel, randomised placebo-controlled, dietary intervention feasibility trial. Patients with radiographic knee osteoarthritis (Kellgren-Lawrence score 2-3), with pain of at least 4 on a scale of 0-10 were recruited. The intervention was a high glucoraphanin broccoli, (source of SFN), or a matched placebo (no SFN) soup. Pain and measures of physical function were measured at baseline, 6 and 12 weeks. ResultsThe mean WOMAC pain score (scale 0 - 20) was decreased by 4.2 (95% CI: 1.03,7.38) following intervention, Similar patterns of improvement were observed for other pain and function outcome measures. Study data, sample collections and intervention adherence were 100% compliant except where COVID restrictions applied. Acceptability for randomisation was 100% and acceptability for the intervention was 92%. There were three related adverse events, two of which were expected. ConclusionsHigh glucosinolate broccoli soup is a novel approach to managing OA that is widely accessible and can be used on a large scale. This study shows that it is an acceptable way of delivering dietary bioactives and has potential for therapeutic benefit. The primary outcome of pain improved in the intervention group compared to the placebo and the confidence interval encompassed the minimal clinically important difference. The data provide justification for proceeding to a large scale, appropriately powered intervention trial.

BackgroundBiologics and Janus kinase (JAK) inhibitors carry specific risks for Ankylosing Spondylitis patients at risk of tuberculosis infection or those with contraindications such as a history of cancer, there is an urgent need to explore safe and effective alternative treatment options. AimsTo evaluate the efficacy and safety of Iguratimod combined with Yunke injection in the treatment of ankylosing spondylitis at risk of tuberculosis infection or those with a history of cancer. Study DesignRetrospective cohort study. MethodsA retrospective study was conducted on 48 patients with ankylosing spondylitis who had received treatment over the past 3 years and had a history of tuberculosis infection or malignancy. Their treatment regimens and therapeutic outcomes were analyzed, with particular attention to the progression of tuberculosis and malignancy. ResultsThere was 30 patients receiving Iguratimod combined with Yunke injection treatment, and non-steroidal anti-inflammatory drugs (NSAIDs) were added when pain was severe,referred to as the observation group; 18 patients took Iguratimod and NSAIDs, referred to as the contral group. After treatment of 24 months, both groups showed significant improvements in Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Erythrocyte Sedimentation Rate (ESR), and C-Reactive Protein (CRP), and overall levels could achieve low disease activity. However, the improvement of observation groupin was better than that in the control group, P<0.05. Moreover, the use of NSAIDs in the observation group was significantly less than that in the control group, P<0.001. ConclusionThis study shows that Iguratimod combined with Yunke injection has good efficacy in patients with ankylosing spondylitis who cannot use biologics or JAK inhibitors, not only alleviating pain and morning stiffness but also slowing radiographic progression and reducing the dose of NSAIDs. The combination has a synergistic effect and does not increase adverse reactions. This therapy provides a novel option for patients with specific ankylosing spondylitis.

ObjectivesTo evaluate and compare the individual therapeutic efficacy of NICE-recommended physical activity (PA) and pharmacological interventions on pain amongst adults with rheumatoid arthritis (RA). MethodsA systematic-review and meta-analysis of studies published between March 1988 and April 2025 was conducted across seven databases; AMED, MEDLINE, CINAHL Plus, SPORTDiscus, EMBASE, Google Scholar, Web of Science, and reference lists. Included were monotherapeutic randomised controlled trials (RCTs) of DMARDs, NSAIDS, analgesics, aerobic and/or resistance training for managing pain perceptions; measured as change in pre-and-post-intervention scores using the visual analogue scale (VAS). Participants were aged [&ge;]18 years whose condition met American College of Rheumatology (ACR; 1987/2010) RA-criteria. Pooled meta-analyses results were presented as mean differences (MDs) and 95% confidence-intervals (95% CIs). Risk of bias (ROB) and certainty of evidence were assessed with the ROB 2 tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ResultsSearches identified 3286 articles. 25 trials were selected for inclusion (6468 participants); 14 RCTs of 11 aerobic-and/or-resistance-training programs (n=916), three yoga regimes, an individual joint-protection programme, a trial of Rocabado exercises, and 11 RCTs of 21 DMARD/NSAID monotherapies (n=5552); baricitinib, celecoxib, filgotinib, hydroxychloroquine, ketoprofen, leflunomide(n=2), methotrexate, naproxen (n=2), sarilumab, sulphasalazine, tofacitinib, and upadacitinib. Weighted mean differences in pain perceptions for behavioural and pharmacological interventions were -2.47mm (95% CI: -3.14 - -1.81, p<0.00001) and -11.20mm (95% CI: -11.35 - -11.05, p<0.00001) respectively. ConclusionDespite inconsistent control of medication histories and PA-prescription, adherence to behavioural and pharmacological interventions can successfully alleviate pain. First-line management using DMARDs or NSAIDs appears to be more effective than yoga, Rocabado exercises, or aerobic and/or resistance training alone. Systematic review registration numberCRD420251069339 Key MessagesO_LIBoth pharmacological and physical activity interventions can successfully reduce pain perceptions amongst patients with RA. C_LIO_LIIndependent use of DMARDs or NSAIDs appears to alleviate pain more than aerobic and/or resistance-training. C_LI

IntroductionPotassium inadequacy (diet and body storage) may adversely affect rheumatoid arthritis (RA) and is sparsely reported. We evaluated the therapeutic benefits (RA) of food-based potassium intake, recommended daily allowance (RDA), and higher. ObjectiveTo evaluate pain reduction by oral potassium in chronic RA Methods172 consenting and eligible symptomatic patients (median duration 6.5 years) on ongoing standard care were randomized in a single-center study (80% power, significant p < 0.05) - Arm A (vegetarian diet as per the India RDA for potassium), Arm B (Arm A diet plus novel potassium food supplement) and Arm C (regular diet, control). Efficacy and safety, and diet intake (three-day recall, Food Composition tables) were assessed (blinded) at monthly intervals till 16-week of study completion and statistically analyzed using standard methods. Study groups were found matched and showed inadequate baseline dietary potassium (RDA). On study completion, the median daily potassium intake was 2959 mg in Arm A, 6063 mg in Arm B, and 2553 mg in Arm C. Study subjects remained normokalemic at all evaluations. Overall, the background medication remained stable. Results155 patients (90.1%) completed the study. Adverse events were mild. On comparison, the improvement in pain (primary efficacy) on study completion was significant in Arm B as per protocol analysis; the mean change in pain visual analog scale from baseline was -2.23 (95% confidence interval -2.99 to -1.48). Arm B showed impressive improvement in joint function. High potassium intake predicted low pain (Likelihood ratio 2.9, logistic regression). Compliance (intervention), diet recall, medication, complex nature of dietary intervention/other nutrients, and lack of placebo were potential confounders to ascertain the effectiveness of potassium. ConclusionA planned vegetarian diet and food supplement intervention with a predominantly increased potassium intake significantly reduced chronic RA pain. This adjunct treatment was found safe and well tolerated. However, it requires further validation. Trial RegistrationClinical Trial Registry of India- CTRI/2022/03/040726 KEY MESSAGE What is already known on the topic?O_LIRA is predominantly managed with drug therapy and diet is often neglected C_LIO_LIRA is complicated by hypertension and other cardiovascular disorders, and osteoporosis which may benefit from potassium intervention. C_LIO_LIPotassium and potassium ion channels are important the pathophysiology of pain (and probably inflammation) C_LIO_LIPatients of RA may be deficient in potassium due to inadequate diet or sarcopenia C_LI What does this study add?O_LIPotassium-rich vegetarian diet and a novel high-potassium food supplement significantly reduced pain in chronic RA on supervised standard drug care. C_LIO_LISeveral participants showed improved joint function and better blood pressure status C_LIO_LIHigher potassium intake based on food and diet was safe and well tolerated C_LI How this study might affect research, practice, or policy?O_LIPotassium rich predominantly vegetarian diet should be advocated in the management of RA as an adjuvant C_LIO_LIA judicious use of high potassium food supplement along with suitable diet may benefit difficult and chronic RA C_LIO_LIThe current guidelines on oral potassium intake in RA and other medical disorders need to be revised and call for more research C_LI

IntroductionThere is limited information on the effectiveness of COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods136 consecutive patients with rheumatic diseases who never had a diagnosis of COVID-19 previously, and had completed vaccination with either the ChAdOx1 or BBV152 vaccines were recruited. Their IgG antibody titres to the Spike protein were estimated 1 month after the second dose. Results102 patients had AIRD while the 34 had non-AIRD. Lesser patients with AIRD (92/102) had positive antibodies titres than ones with non-AIRD(33/34) [p<0.001]. Amongst patients who received the ChAdOX1 vaccine, the AIRD group had lower antibody titres. Although the AIRD patients receiving BBV152 had similarly lower titres numerically, this did not attain statistical significance probably due to lesser numbers. Comparing the two vaccines, 114(95%) of those who received ChAdOx1 (n=120) and 11(68.7%) of those who received BBV152(n=16) had detectable antibodies [p=0.004]. Antibody titres also were higher in ChAdOx1 recipients when compared to BBV152. To validate the findings, we estimated antibody titres in 30 healthy people each who had received either vaccine. All 30 who had received ChAdOX1 and only 23/30 of those who had received BBV152 had positive antibodies (p=0.011). ConclusionIn this preliminary analysis, patients with AIRD had lower seroconversion rates as well as lower antibody titres as compared to patients with non-AIRD. Also,the humoral immunogenicity of the BBV152 vaccine appears to be less than that of the ChAdOX1 vaccine. Validation using larger numbers and testing of cellular immunity is urgently required.

IntroductionCost and drug toxicity often deter prolonged therapeutic use of anti-TNF agents in ankylosing spondylitis (AS). A planned study was completed to endorse our clinic-based observation of long-term relief following short-term administration of an anti-TNF agent. Methods50 consenting patients with symptomatic active chronic AS under rheumatology care in a community clinic were enrolled; naive for anti-TNF. 40 mg standard biosimilar Adalimumab (Bs-ADA, Exemptia) was injected subcutaneously every fortnight for six injections (10 weeks). Patients were monitored at several predetermined time points. Improvement was assessed with standard indices (Assessment Spondyloarthritis International Society/ASAS and Bath). An intention to treat analysis was performed: significant p <0{middle dot}05 ResultsPatients showed early and substantial significant improvement in pain, NSAID requirement, function, and in several indices (ASAS 20 & 40, ASAS partial remission, BASDAI, BASFI, ASDAS) which persisted after stopping injections. 84% and 52 % of patients respectively showed ASAS 20 improvement at weeks 12 and 48: corresponding to ASAS partial remission at 34% and 24%. Over 50% of patients maintained prolonged improvement and provided proof of concept (defined apriori). Serum Interleukin-6 assay showed a sharp reduction at 24 weeks. None developed TB or serious drug toxicity. 11 patients withdrew (mostly inadequate response). The absence of control was a limitation. ConclusionA ten-week administration of biosimilar adalimumab in difficult-to-treat AS showed early substantial improvement which often persisted for 24 weeks. This unconventional strategy was socioeconomically appealing. It merits further validation and acceptance, especially in resource strained settings.

Background.Autoimmune disease patients on immunosuppressants exhibit reduced humoral responses to primary COVID-19 vaccination. Booster vaccine responses and the effects of holding immunosuppression around vaccination are less studied. We evaluated the efficacy and safety of additional vaccination in mycophenolate mofetil/mycophenolic acid (MMF/MPA)-, methotrexate (MTX)-, and B cell-depleting therapy (BCDT)-treated autoimmune disease patients, including the impact of withholding MMF/MPA and MTX. Methods.In this open-label, multicenter, randomized trial, 22 MMF/MPA-, 26 MTX-, and 93 BCDT-treated autoimmune disease patients with negative or suboptimal antibody responses to initial COVID-19 vaccines (BNT162b2, mRNA-1273, or AD26.COV2.S) received a homologous booster. MMF/MPA and MTX participants were randomized (1:1) to continue or withhold treatment around vaccination. The primary outcome was the change in anti-Wuhan-Hu-1 receptor-binding domain (RBD) concentrations at 4 weeks post-additional vaccination. Secondary outcomes included adverse events, COVID-19 infections, and autoimmune disease activity through 48 weeks. Results.Additional vaccination increased anti-RBD concentrations in MMF/MPA and MTX patients, irrespective of whether immunosuppression was continued or withheld. BCDT-treated patients also demonstrated increased anti-RBD concentrations, albeit lower than MMF/MPA- and MTX-treated cohorts. COVID-19 infections occurred in 30-46% of participants, were predominantly mild, and included only two non-fatal hospitalizations. Additional vaccination was well-tolerated, with low frequencies of severe disease flares and adverse events. Conclusion.Additional COVID-19 vaccination is effective and safe in immunosuppressant-treated autoimmune disease patients, regardless of whether MMF/MPA or MTX is withheld. Trial Registration. ClinicalTrials.gov (NCT#05000216)