Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Validation of claims-based algorithms for rheumatoid arthritis in Japan: Results from the VALIDATE-J study.

AIM: Validity of Algorithms in Large Databases: Infectious Diseases, Rheumatoid Arthritis, and Tumor Evaluation in Japan (VALIDATE-J) study examined algorithms for identifying rheumatoid arthritis (RA) in Japanese claims data. METHODS: VALIDATE-J was a multicenter, cross-sectional retrospective study. Disease-identifying algorithms were used to detect RA diagnosed between January 2012 and December 2016 using claims data from two Japanese hospitals. An RA diagnosis was confirmed using one of four gold standard definitions. Positive predictive values (PPVs) were calculated for prevalent (regardless of baseline RA-free period) and incident (preceded by a 12-month RA-free period) cases. RESULTS: Of patients identified using claims-based algorithms, a random sample of 389 prevalent and 134 incident cases of RA were included. Cases identified by an RA diagnosis, no diagnosis of psoriasis, and treatment with any disease-modifying antirheumatic drugs (DMARDs) resulted in the highest PPVs versus other claims-based treatment categories (29.0%-88.3% [prevalent] and 41.0%-78.2% [incident]); cases identified by an RA diagnosis, no diagnosis of psoriasis, and glucocorticoid-only treatment had the lowest PPVs. Across claims-based algorithms, PPVs were highest when a physician diagnosis or decision by adjudicators (confirmed and probable cases) was used as the gold standard and were lowest when American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria were applied. PPVs of claims-based algorithms for RA in patients aged ≥66 years were slightly higher versus a USA Medicare population (maximum PPVs of 95.0% and 88.9%, respectively). CONCLUSION: VALIDATE-J demonstrated high PPVs for most claims-based algorithms for diagnosis of prevalent and incident RA using Japanese claims data. These findings will help inform appropriate RA definitions for future claims database research in Japan.

Association of large joint involvement at the start of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors with disease activity and drug retention in patients with rheumatoid arthritis: The ANSWER cohort study.

AIM: To investigate the association of large joint involvement (LJI) with disease activity and drug retention in patients with rheumatoid arthritis (RA) who started receiving a biological disease-modifying antirheumatic drug or Janus kinase inhibitor. METHODS: Patients with RA from a Japanese multicenter observational registry were enrolled. Our definition of large joints included the shoulder, elbow, hip, knee, and ankle joints. Linear mixed-effects models were used to examine changes in the clinical disease activity index (CDAI) score at Week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We examined the potential effect modifications of changes in the CDAI by baseline characteristics. RESULTS: Overall, 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in CDAI from baseline at Week 24 (difference in change in CDAI: -5.84 [-6.65 to -5.03], p < .001), CDAI was significantly higher in patients with LJI over time. Retention rates were similar in both groups. The association of LJI with changes in disease activity was more prominent in patients with a short disease duration, negative anti-citrullinated peptide antibodies, and interleukin-6 receptor inhibitor (IL-6Ri) use. CONCLUSION: Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat-to-target strategy using an IL-6Ri may be beneficial for patients with LJI.