Background/Purpose: Data are very limited concerning the safety of multiple retreatments with rituximab (RTX) in rheumatoid arthritis in common practice.

Methods: This is a multicenter open-label observational study of patients with RA according to 1987 ACR criteria who were initiating RTX and enrolled in the French Society of Rheumatology prospective registry AIR (AutoImmunity and Rituximab) Severe adverse events (death, serious infection, and cancer) were validated by chart review by three experts. A serious infection was defined as an infection occurring during the 12 months after a rituximab infusion and requiring hospitalization and/or intravenous antibiotics and/or resulting in death. Cancers were considered in the analysis regardless of their time of occurrence, even after registry drug discontinuation. For serious infections, exposure time was defined as the time between inclusion and the first occurrence of serious infection, end of follow-up, or last infusion of rituximab plus 12 months for rituximab. For cancers and deaths, exposure time was defined as the time between inclusion and first occurrence of an event or end of follow-up.

Results: Median age and disease duration before RTX in the 1986 enrolled patients were 58 [50-67] and 11 [6-18] years, respectively. 14% of patients had a history of cancer, 34.6% had a history of serious or recurrent infections. Median number of previous conventional DMARDs and of biologics were 3 [2 ;4] and 2 [1 ;2], respectively. Median DAS28-ESR at RTX initiation was 5.53 [4.72; 6.38]. 65.7% of patients initiated RTX in combination with a synthetic DMARD (methotrexate :75.6%). 78.7% of patients received concomitant oral corticosteroids (median dose 10 [7; 15] mg/day. Current total follow-up of the 1984 patients was 10 545 patient-years (mean follow-up : 5.3 years). 1280 patients have received less than 5 cycles of RTX, 551 patients between 5 and 9 cycles and 153 patients 10 cycles or more. Overall, 369 serious infections occurred (5.2 /100 patient-years) : 195 in patients treated with less than 5 cycles of RTX (6.1/100 patient-years), 134 patients treated with 5 to 9 cycles (4.0/100 patient-years) and 40 in patients treated with more than 10 cycles (4.0/100 patient-years). 134 cancers occurred (1.3/100 patient-years) including 85 in patients treated with less than 5 cycles of RTX 1.4/100 patient-years), 42 in patients treated with 5 to 9 cycles (1.2/100 patient-years) and 7 in patients treated with more than 10 cycles (0.7/100 patient-years). 196 deaths occurred (1.9/100 patient-years) including 177 in patients treated with less than 5 cycles of RTX (3.0 /100 patient-years), 17 in patients treated with 5 to 9 cycles (0.5/100 patient-years) and 2 in patients treated with more than 10 cycles (0.2/100 patient-years). RTX was discontinued in 820 patients treated with less 5 cycles, 155 treated with 5 to 9 cycles and 19 in patients treated with 10 cycles or more. Discontinuation was related to serious adverse events in 105 (2.8%) patients treated with less 5 cycles, 29 (18.7%) patients treated with 5 to 9 cycles and 4 (21.0%) patients treated with 10 cycles or more.

Conclusion: The rate of serious adverse events seems similar in patients with multiple retreatments with RTX as in patients less frequently retreated. However, these results must be interpreted with caution taking into account the depletion of susceptible effect (patients who remain on a drug are those who can tolerate it).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-multiple-retreatments-with-rituximab-in-real-life-long-term-registry-data-from-1984-patients-with-rheumatoid-arthritis/