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Objective: To investigate the prevalence of poly‐refractory rheumatoid arthritis (RA) defined as failure of all biological (b)/targeted synthetic (ts)‐disease‐modifying drugs (DMARDs). To further investigate whether patients with persistent inflammatory refractory RA (PIRRA) and noninflammatory refractory RA (NIRRA), determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult‐to‐treat RA (D2T‐RA) and poly‐refractory RA groups. Methods: A cross‐sectional study of 1,591 patients with RA on b/tsDMARDs that evaluated D2T‐RA criteria and subclassified as poly‐refractory if inefficacy/toxicity to at least one drug of all classes. PIRRA was defined if US synovitis in one or more swollen joint and NIRRA if absent. Univariate tests and multivariate logistic regression were conducted to investigate factors associated with poly‐refractory, PIRRA, and NIRRA phenotypes. Results: 122 of 1,591 were excluded due to missing data. 247 of 1,469 (16.8%) had D2T‐RA and only 40 of 1,469 (2.7%) poly‐refractory RA. This latter group had higher disease activity score 28 C‐reactive protein (CRP) (median 5.4 vs 5.02, P < 0.05), CRP levels (median 13 vs 5 mg/l, P < 0.01), and smoking (ever) rates (20% vs 4%, P < 0.01) compared with other D2T patients. Smoking was associated with poly‐refractory RA (odds ratio 5.067, 95% CI 1.774–14.472, P = 0.002). Of 107 patients with D2T‐RA with recent US, 61 (57%) were PIRRA and 46 (43%), NIRRA. Patients with NIRRA had elevated body mass index (median 30 vs 26, P < 0.001) and higher fibromyalgia prevalence (15% vs 3%, P < 0.05), lower swollen joint count (median: 2 vs 5, P < 0.001), and lower CRP levels (5 vs 10, P < 0.01). Conclusion: Only 2.7% of D2T‐RA failed all classes of b/tsDMARDs. Among D2T‐RA, less than 60% had objective signs of inflammation, representing a target for innovative strategies. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of non-medical switch from rituximab originator (RTX-O) to biosimilar (RTX-B) in patients with RA. Methods Between October 2017 and October 2019, all patients on RTX-O in our centre requiring re-treatment were switched to RTX-B unless declined by the patient or specified by the treating clinician. Switch strategy effectiveness was assessed retrospectively using DAS28-CRP(3) and RTX retention, with patients remaining on RTX-O as a comparator group. Results The number of patients switching to RTX-B was 255/337 (75.7%) while 82 (24.3%) remained on RTX-O. There was no difference in DAS28-CRP(3) 4 months post-RTX-B switch vs the same time point post-RTX-O previous cycle (paired data available in 60%). Eighteen-month retention estimates were 75.6% (95% CI: 69.4, 80.7%) for RTX-B group and 82.3% (95% CI: 70.4, 89.8%) for RTX-O [adjusted hazard ratio 1.52 (95% CI: 0.85, 2.73)]. The number of patients who discontinued RTX-B for loss of effectiveness (LOE) was 42/255 (16.5%), five (2.0%) for adverse effects (AEs). Risk of RTX-B discontinuation was associated with comorbidities and ≥2 previous biologic DMARDs. Risk of adverse outcome RTX cessation was associated with comorbidities, and reduced risk with number of previous RTX-O cycles and pre-switch cycle B cell depletion. The number of patients who switched back to RTX-O was 34/255 (13.3%) (LOE: 30, AEs: 4), while 13/255 (5.1%) started other biologic/targeted synthetic DMARDs. Of patients who switched back for LOE, 28/30 remained on RTX-O at a mean 7.7 months follow-up. Conclusion Non-medical switch to RTX-B was largely effective. Factors associated with RTX-B discontinuation, including comorbidities, previous biologic DMARDs, and RTX-O treatment history, may inform switch decisions. Most patients who switched back to RTX-O for LOE remained on treatment at short-term follow-up. [ABSTRACT FROM AUTHOR]

For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA. [ABSTRACT FROM AUTHOR]

Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; however, it is recommended that patients can taper therapy, with a view to discontinuing and achieving drug-free remission if treatment goals are maintained. This narrative review aims to present the current literature on drug-free remission in rheumatoid arthritis, with a view to identifying which strategies are best for disease-modifying anti-rheumatic drug (DMARD) tapering and to highlight areas of unmet clinical need. Methods: We performed a narrative review of the literature, which included research articles, meta-analyses and review papers. The key search terms included were rheumatoid arthritis, remission, drug-free remission, b-DMARDS/biologics, cs-DMARDS and tapering. The databases that were searched included PubMed and Google Scholar. For each article, the reference section of the paper was reviewed to find additional relevant articles. Results: It has been demonstrated that DFR is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. Conclusions: DFR in RA may be an achievable goal in certain patients. This carries importance in reducing medication-induced side-effects and potential toxicity, the burden of taking treatment if not required and cost effectiveness, specifically for biologic therapy. Prospective studies of objective biomarkers will help facilitate the prediction of successful treatment discontinuation. [ABSTRACT FROM AUTHOR]