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.