Risk factors for relapse in ANCA ‐associated vasculitis among patients with relapse after induction of remission with rituximab

Objective To determine risk factors for relapse of ANCA‐associated vasculitis (AAV) after re‐induction of remission with rituximab and discontinuation of maintenance therapy. Methods This is a post‐hoc analysis of the RITAZAREM clinical trial. Patients 15 years or older with AAV and a positive test for anti‐proteinase‐3 (PR3‐) or anti‐myeloperoxidase (MPO)‐ANCA who achieved remission after re‐induction with rituximab and glucocorticoids were randomized at month 4 to receive continued rituximab or azathioprine for a maintenance period up to 24 months, followed by observation until relapse or up to 48 months. Generalized estimating equations logistic regression identified baseline and time‐varying risk factors for relapse by the next visit for the two study phases: maintenance (months 4‐24) and off‐treatment (months 24‐48). Results Among 170 patients (median (IQR) age 59 (48‐68) years, disease duration 5 (2‐10) years), 99 relapses occurred (46 during maintenance). During maintenance, musculoskeletal involvement (odds ratio (OR) [95% confidence interval (CI)]: 2.8 [1.1, 7.2], p=0.03) and higher patient global assessment (OR [95% CI]: 1.1 [1.0, 1.2], p=0.04) were associated with relapse. During the off‐treatment phase, presence of CD19+ B‐cells (OR [95% CI]: 2.5 [1.2, 5.1], p=0.01) and reappearance of ANCA (OR [95% CI]: 3.2 [1.3, 7.7], p=0.01) were each associated with higher relapse risk. Multivariable analysis identified markers of inflammation (changes in platelets, white blood cells, and immunoglobulin A) associated with relapse. Conclusions Risk factors for relapse in AAV vary by treatment phase. Monitoring markers of inflammation and immune reconstitution may identify patients at risk for relapse, particularly after treatment withdrawal.