OBJECTIVES:Rituximab (RTX) is a standard maintenance therapy for antineutrophil cytoplasmic antibody-associated vasculitis. Its efficacy in Japan remains unclear, where microscopic polyangiitis (MPA) predominates and clinical characteristics differ from Western-dominated randomized controlled trial (RCT) populations. METHODS:Japanese patients with MPA or granulomatosis with polyangiitis (GPA) enrolled in a nationwide registry were included. Exposure was RTX use during maintenance therapy. The primary endpoint was major relapse-free survival at 104 weeks. The secondary endpoint was any relapse-free survival (major or minor) at 104 weeks. Baseline differences were adjusted using inverse probability of treatment weighting based on key demographic and disease-related covariates. RESULTS:A total of 389 patients were analysed, with 85 in the RTX group. The RTX group included a higher proportion of GPA cases (37/85 vs. 74/304), resulting in baseline imbalance. After inverse probability of treatment weighting, no major relapses were observed in the RTX group, whereas the major relapse-free survival at 104 weeks was 94.8% in the non-RTX group. The RTX group showed significantly higher any relapse-free survival at 104 weeks (95.4% versus 83.3%; HR for any relapse, 0.27; 95% CI, 0.09-0.74; P = .02). CONCLUSIONS:Our findings suggest that RTX may be an effective option for remission maintenance in Japanese patients with MPA or GPA.
Abstract Objectives Clinical heterogeneity in ANCA-associated vasculitis (AAV) is not fully captured by conventional disease subtypes or ANCA serotypes. We aimed to identify data-driven, clinically meaningful disease phenotypes based on patterns of organ involvement in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), and to evaluate their prognostic and therapeutic implications. Methods We conducted a multicentre retrospective cohort study using two nationwide Japanese registries (J-CANVAS as derivation; JPVAS as validation). Ensemble clustering was applied to high-dimensional organ involvement data derived from the Birmingham Vasculitis Activity Score and additional clinically relevant manifestations. The resulting clusters were replicated using classification and regression tree (CART) across the derivation and validation cohorts, and associations between cluster memberships and clinical outcomes (overall survival and relapse), as well as response to induction therapy, were evaluated. Results Among 726 patients with newly diagnosed MPA or GPA, ensemble clustering identified four reproducible clinical phenotypes: (a) renal-dominant without interstitial lung disease (ILD); (b) renal-dominant with ILD; (c) systemic multi-organ and (d) ear, nose and throat (ENT)-dominant. CART reproduced these clusters with good concordance. Overall survival and relapse incidence differed across clusters. The ENT-dominant cluster demonstrated favourable survival but a higher relapse risk and showed a trend towards improved relapse-free survival with rituximab compared with CYC, even among MPO-ANCA-positive patients. Conclusion Organ involvement-based ensemble clustering identifies clinically meaningful and reproducible AAV phenotypes with distinct prognostic and therapeutic profiles. Integrating phenotypic patterns with ANCA serotype may enhance risk stratification and support more individualized management strategies in AAV.
BACKGROUND:Bronchiectasis is known to be more frequently observed in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) compared to the general population. However, its association with patient outcomes and the potential influence of immunosuppressive treatment on this association remain unclear. METHODS:We conducted a multicenter observational study using data from the Japan Collaborative Registry of ANCA-Associated Vasculitis (J-CANVAS). Adult patients with newly diagnosed or relapsing MPA or GPA between January 2017 and March 2023 were included. The exposure was clinically apparent bronchiectasis at baseline. Primary outcomes were serious infections and all-cause mortality; relapses were examined as a secondary outcome over 52 weeks. For each outcome, incidence rate ratios (IRRs) were estimated using multivariable Poisson regression models conditioned on confounding factors, incorporating follow-up time as an offset term. Interactions between initial treatment (prednisone dose, rituximab, cyclophosphamide, intravenous methylprednisolone, and plasma exchange) and bronchiectasis were also evaluated. RESULTS:Among 844 patients (MPA: 614; GPA: 230), 68 (8.1%) had bronchiectasis. During the follow-up period, there were 122 serious infections among 101 patients, 48 deaths, and 85 relapses among 72 patients. Adjusted IRRs for patients with bronchiectasis were 2.18 (95% CI: 1.25-3.83) for serious infections, 3.07 (1.41-6.66) for mortality, and 1.58 (0.77-3.24) for relapse. No clear interaction was detected between specific treatments and bronchiectasis. CONCLUSIONS:Bronchiectasis was associated with increased risks of serious infections and mortality in patients with MPA and GPA. However, we did not detect clear interaction by initial treatment, suggesting that avoiding specific therapies may not be necessary.
OBJECTIVES:To evaluate the real-world effectiveness of rituximab (RTX) and intravenous cyclophosphamide (IVCY) compared to non-use for remission induction in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS:This observational study emulated a target trial using data from the Japan Collaborative Registry of ANCA-associated Vasculitis. Patients aged ≥20 years with newly diagnosed or relapsing MPA or GPA (2017-23) were included. RTX or IVCY use within 4 weeks defined the treatment group; others formed the control group. The primary outcome was failure to achieve remission at week 24 (Birmingham Vasculitis Activity Score = 0 and prednisolone ≤ 10 mg/day). Secondary outcomes included a composite of death, kidney failure, and relapse, and serious infection. In inverse probability weighted population, risk ratios were estimated using modified Poisson regression. RESULTS:Among 544 patients (MPA: 413, GPA: 131), 63.6% received RTX or IVCY. The risk ratio for failure to achieve remission was 0.72 (95% CI: 0.61-0.85), and for the composite outcome was 0.57 (95% CI: 0.33-0.97), and for serious infection was 1.03 (95% CI: 0.47-2.25). Results were robust in sensitivity analyses. CONCLUSIONS:RTX and IVCY improved short-term outcomes in MPA and GPA without increasing infection risk, supporting their recommendation as standard therapy.
OBJECTIVES:Rituximab (RTX) is a key treatment for ANCA-associated vasculitis (AAV), but RTX-induced acute thrombocytopenia (RIAT) remains a concern. We aimed to evaluate the risk and risk factors of RIAT in patients with AAV undergoing RTX induction therapy. METHODS:Patients with new-onset microscopic polyangiitis or granulomatosis with polyangiitis who received RTX in a nationwide multicentre registry in Japan were included. RIAT was defined by platelet count reductions within 28 days post-RTX. Risk factors for RIAT were identified by using logistic regression with stepwise selection, and prediction models were developed. Model performance was assessed using C-statistics. RESULTS:Among 175 patients with AAV receiving RTX, RIAT occurred in 35.4% of them. Diabetes mellitus (odds ratio [OR] = 4.96), cardiac disease (OR = 3.57), low platelet count (OR = 1.04 per 104/μl decrease), increased serum creatinine (OR = 1.44 per 1 mg/dl increase), low albumin (OR = 2.33 per 1 g/dl decrease), and high KL-6 (OR = 1.09 per 100 U/ml increase) were identified as significant predictors. A predictive model incorporating these factors achieved a C-statistic of 0.817. CONCLUSION:RIAT is a frequent complication of RTX induction in patients with AAV, with diabetes mellitus and cardiac disease being strong risk factors. Our predictive model enables risk assessment for RIAT, allowing clinicians to optimize treatment strategies.
