Background/Purpose: Serious infections in patients with rheumatoid arthritis (RA) treated with  rituximab (RTX) are slightly more frequent in common practice than in clinical trials. Morevover, retreatment with multiple cycles might result in hypogammaglobulinemia, which is associated with an increased risk of serious infections. We therefore addressed this issue in the “Auto Immunity and Rituximab” (AIR) registry.

Methods: The AIR registry is an independent multicenter prospective 7-year registry promoted by the French Society of Rheumatology. Serious adverse events are validated by copy charts by the coordinators of the registry. Serious infections are defined as infections which required hospitalization, intravenous antibiotics or resulted in death. All serious infections occurring in the 12 months following a RTX infusion are considered to occur on RTX therapy.

Results: 1985 patients with RA have been included. Baseline characteristics of the patients are the following : mean age: 58 years, women: 79%,  disease duration: 19 years, RF-positivity: 79.5%, anti-CCP positivity: 72,6%, number of previous synthetic DMARDs: 3, 22% of patients without prior anti-TNF, 13% of patients with history of cancer, 34.7% of patients with previous serious or recurrent infections, 65.8% of patients treated with a concomitant synthetic DMARD, 77.2% with corticosteroids (mean dose: 12 mg/d), DAS28 at initiation of RTX: 5.6. 1977 patients have already had at least 1 follow-up visit, with a mean follow-up of 3 years (5865 patient/years)

– Retreatment with RTX: 70.6% of patients with RA were retreated (at least 2 cycles of RTX) : ≥2 cycles: 1405 patients; ≥3 cycles: 1043 patients; ≥4 cycles: 763 patients; ≥5 cycles: 532 patients; ≥6 cycles: 330 patients)

– Safety: 95 deaths, 81 cancers, and 281 serious infections occurred. 961 patients (48.4%) discontinued RTX (initiation of a new biological, death, or no infusion in the 18 months preceding last follow-up visit) including 557 patients for inefficacy, 100 for adverse events (including 91 for a serious infection, 32.4% of the patients with serious infections), and 294 patients for other reasons.  96 serious infections occurred after the 1^st cycle (4.8% of patients), 69 after the 2d cycle (4.9%), 38 after the 3d (3.6%) , 32 after the 4^th (4.2%), 20 after the 5^th (3.8%), 8 after the 6^th  (2.4%), respectively,  resulting in RTX discontinuation in 36 (37.5% of the serious infections occurring after 1^stcycle) , 28 (40.5%), 11 (28.9%), 10 (31.2%), 3 (15.0%), 2 (25.0%), after cycle 1 to 6, respectively.

Conclusion: In common practice, the proportion of patients with serious infections remains stable  over cycles of RTX despite the increasing risk of hypogammaglobulinemia. It could be partly related to the depletion of the more susceptible patients with time. However, approximately two thirds of patients who experienced a serious infection did not discontinue RTX. Analysis of the contribution of the improvement of disease activity and decrease of corticosteroid dosage to this stable  risk of serious infections, is currently ongoing.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-rate-of-serious-infections-remains-stable-in-patients-with-multiple-retreatments-in-real-life-data-from-the-auto-immunity-and-rituximab-air-registry/