327. LONG-TERM SAFETY OF RITUXIMAB IN GRANULOMATOSIS WITH POLYANGIITIS OR MICROSCOPIC POLYANGIITIS: RESULTS OF THE FOUR-YEAR RITUXIMAB IN ANCA-ASSOCIATED VASCULITIS REGISTRY Free

Background: Potential therapy-related toxicities are important causes of morbidity in patients with the ANCA-associated vasculitides granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Long-term safety studies of rituximab in GPA/MPA are limited.

Methods: Analysis of RaVeR (NCT01613599), an open-label real-world study of adult patients with GPA or MPA receiving rituximab (dosing regimen determined by treating physician according to standard practice and discretion), was

conducted after ⩽4 years of observation or until withdrawal of consent, loss to follow-up or death. Adverse events (AEs) of interest included serious AEs (SAEs), serious infection events (SIEs), infusion- related reactions (IRR), serious cardiac or vascular events and malignancies. Crude incidence rates and 95% CI were calculated.

Results: A total of 97 patients (338 patient-years [PYs]; median age 58.0 years; mean [SD] baseline VDI 2.0 [2.7]) received rituximab (mean of 8 infusions [range 1-28]). Median duration on study was 3.94 (range 0.05-4.32) yrs. 74% of patients completed the study. 91% of patients were ANCA-positive and 74% had GPA. 20% were receiving rituximab plus cyclophosphamide at baseline. During the study, 38 patients had 94 SAEs, 14 had 24 SIEs, and 10 had 17 serious cardiac events, most of which were arrhythmias (described in the existing label for rituximab; Table). Six patients had 8 serious vascular events and 3 patients had malignancy-related events. There were no serious IRRs or SAEs within 24 hours of rituximab infusion. There were 9 deaths; none were considered by the treating physician to be related to rituximab. Causes of death included septic shock, interstitial lung disease, congestive heart failure, cardio-respiratory arrest, lung adenocarcinoma and 4 of unknown etiology. The severe disease flare (worsening disease activity prompting treatment) rate was 4.44/100 PYs (95% CI: 2.49-7.33). Among patients who received rituximab repeat treatment, the rates of SAEs (23.90/100 PYs) and SIEs (6.07/100 PYs) were not increased compared with the overall cohort.

Conclusion: In this cohort study there were no new safety findings related to the use of rituximab for GPA or MPA, and rates for any AE, including SIEs, cardiovascular events, malignancies, or fatal AEs did not increase over time with repeated infusions of rituximab. These results are consistent with the known safety profile of rituximab in GPA and MPA and in other autoimmune diseases for which rituximab is approved. RaVeR provides clinicians with long-term, practice-level safety data.

Disclosures: J. Niles: grant/research support: ChemoCentryx; P. Merkel: Grant/research support: Boeringher-Ingelheim, Bristol-Meyers Squibb, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, Kypha TerumoBCT; consultant: AbbVie, Biogen, Boeringher-Ingelheim, Celgene, ChemoCentryx, Genentech/Roche, GlaxoSmithKline, InflaRx, Insmed, Kiniksa, Medimmune/AstraZeneca, Sanofi ; L Mertz: non declared; P. Pordeli: Employee of Roche Products Ltd; P. Lehane: Employee of Roche Products Ltd.; F. Erblang: Employee of: F. Hoffman-La Roche, Ltd. This study was funded by Genentech, Inc.