Extended Follow-Up of Patients Recruited to a Randomized, Controlled Trial of Rituximab vs. Azathioprine, After Rituximab Remission Induction for Patients with Relapsing ANCA-Associated Vasculitis

Background: RTX is an effective remission induction therapy in AAV. However, the effect of RTX is not sustained, and relapse rates are high, especially in patients with a history of relapse. The RITAZAREM trial was an international, open-label, randomized, controlled trial of patients with AAV with relapsing disease comparing the efficacy, after induction of remission with RTX, of repeat dose RTX or AZA as relapse prevention strategies. Methods: Patients with relapsing AAV received induction therapy with RTX and glucocorticoids (GC). If remission was achieved by month 4, patients were randomized 1:1 to receive RTX (1000 mg every 4 months for 5 doses) or AZA (2 mg/kg/day) as maintenance therapy for 24 months. Patients continued to be followed until at least 36 months after enrolment, with a primary outcome of time to disease relapse. The final patient reached month 36 in the trial in November 2019. Results: 190 patients were enrolled and 170 randomized at month 4 (85 to RTX; 85 to AZA): median age = 59 years (range 19-89); prior disease duration = 5.3 years (0.4-38.5); 123/170 (72%) with anti-PR3 ANCA, 47/170 (28%) with anti-MPO ANCA; 104 (61%) enrolled after a severe relapse, 66/170 (39%) after a non-severe relapse; GC induction regimen: 48/170 (28%) higher-dose, 122/170 (72%) lower-dose; 114 (67%) patients had prior renal involvement. We previously presented the results demonstrating the superiority of rituximab over azathioprine during the maintenance treatment period. Results of the follow up phase of the study after discontinuation of maintenance therapy will be presented at the 2020 meeting. Conclusions: The results of the extended phase of RITAZAREM will examine the long-term impact of B cell depletion in patients with AAV on sustaining remission beyond the treatment period, clinical or biomarker factors associated with risk of relapse, and post-treatment safety of prolonged use of rituximab, including a focus on hypoimmunoglobulinemia. Funding: Other NIH Support - The VCRC is funded through collaboration between NCATS, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and has received funding from the National Center for Research Resources (U54 RR019497)., Commercial Support - Genentech/Roche