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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., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Specific guidelines for managing RA patients in clinical remission for ≥6 months on cs-DMARDs are lacking. Tapering of treatment is encouraged, however, without validated biomarkers for success. We aimed to assess the rate of sustained remission after 12 months in patients who either (i) followed structured cs-DMARD tapering or (ii) continued therapy, focusing on the added value of biomarkers as predictors of outcome., Methods: RA patients fulfilling 3v-DAS28CRP<2.6 for ≥6 months on stable cs-DMARD therapy were included. Patients were offered structured tapering, with 117 accepting tapering and 83 continuing therapy. Clinical, ultrasound, immunological (T-cell subsets) and patient-reported outcome (PRO) data were collected. The primary endpoint was the proportion of patients in sustained remission without relapse after 12 months. Regression analyses were used to identify predictors of sustained remission., Results: Of those who tapered, 64% remained in clinical remission after 12 months compared with 80% (p=0.018) of patients on stable treatment. In the tapering group, higher levels of CRP, TJC, % inflammation-related T-cell (IRC) and PROs were associated with flare (all p<0.05), with a trend for total PD (p=0.066). A model predicting sustained remission retained RAQoL, total PD and IRC (85% accuracy, AUROC=0.893, p<0.0001). In the non-tapering group, higher CRP, ESR, SJC and shorter disease duration (all p<0.05) were associated with flare, with no parameter able to predict sustained remission., Conclusions: In the tapering group, the combination of clinical, PRO, US and T-cell parameters demonstrated added value for predicting sustained remission compared with clinical parameters alone. These data may inform best tapering practice.

Background: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are effective in treating inflammatory diseases and have been increasingly utilized over the past decade. Patients who receive bDMARDs have been shown to be at an increased risk for surgical site infection following surgical procedures. The severe consequences of infection following orthopaedic surgery have led to the practice of withholding bDMARDs perioperatively; however, there has been no definitive evidence showing a clear benefit of withholding the use of bDMARDs, and in doing so, patients may be at an increased risk for higher disease activity. As such, the purpose of the present study was to compare the risk of infection, delayed wound healing, and disease flares associated with the use of bDMARDs in patients undergoing orthopaedic surgical procedures., Methods: We performed a systematic literature search of MEDLINE, Embase, and PubMed CENTRAL databases for studies comparing continuing and withholding the use of bDMARDs in patients undergoing orthopaedic procedures. Inclusion criteria were established following the PICO (Population, Intervention, Comparison, and Outcomes) approach: Population = patients who underwent orthopaedic surgical procedures and who were taking bDMARDs. Intervention = withholding the use of bDMARDs. Comparator = continuing the use of bDMARDs. Outcomes = surgical site infection, delayed wound healing, and disease flares. Article titles and abstracts were screened prior to review of the full text. Overall odds ratios (ORs) and associated 95% confidence intervals (CIs) for pooled effects were calculated., Results: Eleven studies met the inclusion criteria, providing data for 7,344 patients, including 2,385 patients who continued and 4,959 who withheld their bDMARDs perioperatively. Continuing bDMARDs was associated with a significantly lower risk of disease flares (OR, 0.22; 95% CI, 0.05 to 0.95; p = 0.04) and nonsignificant increases in surgical site infections (OR, 1.11; 95% CI, 0.82 to 1.49; p = 0.49) and wound complications (OR, 2.16; 95% CI, 0.48 to 9.85; p = 0.32)., Conclusions: The present systematic review highlights the limited evidence supporting the current practice of stopping bDMARDs perioperatively. These findings suggest that patients may not be at an increased risk for developing infection or wound complications if bDMARDs are continued but are at an increased risk for disease flare if bDMARDs are withheld. However, our conclusions are limited by the retrospective and heterogenous nature of the data, and possibly by a lack of study power., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G940)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs)., Methods: This prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score., Results: After vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (p<0.001). Better seroconversion occurred with anti-tumour necrosis factor (TNF) versus RTX (p=0.012) and with age ≤50 (p=0.012). Pre-vaccine SARS-CoV-2 exposure was associated with higher quantitative seroconversion (≥3 antibodies) (p<0.001). In the subgroup of non-seroconverters, a second vaccination produced seroconversion in 54% (19/35), and after a third in 20% (2/10). IFN score analysis showed no change post-vaccine., Conclusion: Patients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses., Competing Interests: Competing interests: BS: Speaker fees for Pfizer and Galapagos, L-AB: Honoraria for UCB, Abbvie and Galapagos, KM: Personal: Abbvie, Lilly, UCB.Grants: Lilly, Gilead, FD: received research support and consultancies, not related to the topic of this manuscript from ABBVIE, AstraZeneca, Boehringer-Ingelheim, Capella, Chemomab, Kymab, Mitsubishi-TanabePaul Emery: Grants : AbbVie, BMS, Lilly, Samsung. Consulting fees: BMS, AbbVie, MSD, Pfizer, Novartis, and Roche. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events:Abbvie, Gilead, Lilly, Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)