Monitoring anti-Rituximab antibodies in myasthenia gravis affects the time to event during Rituximab treatment.

Abstract

Introduction: Rituximab (RTX) effectively manages myasthenia gravis (MG) by reducing relapse rates. Anti-Rituximab antibodies can develop in autoimmune diseases and may lead to RTX resistance. Although RTX infusions are increased, these antibodies do not influence the occurrence of adverse events. We conducted a retrospective study to evaluate how anti-drug antibodies (ADAs) impact treatment efficacy.

Methods: We reviewed 101 MG patients treated with first- or second-line RTX at Nice University Hospital from 2016 to 2023. Clinical assessments were performed quarterly using the Osserman Score (OS). Biological tests included ADA levels, RTX serum levels, CD19+CD27+ memory B cells, and CD19+ cell counts.

Results: Among 101 patients, 38 developed ADAs (37.6%), with a median onset of 433.5 days after the first infusion. The ADA group had significantly more RTX infusions (6.18 vs. 4.29, p=0.002) and more prolonged treatment durations (1908.26 vs. 1441.3 days, p=0.006). No differences in age, gender, or prior immunosuppression were noted. OS scores revealed no significant difference between ADA-positive and ADA-negative patients. The interval between infusions remained consistent before and after the appearance of ADAs.

Discussion: ADAs were found in one-third of MG patients treated with RTX, a higher prevalence than in other conditions. The number of RTX infusions was significantly greater in the ADA-positive group, and the longer is the treatment duration, the higher the likelihood of developing ADAs. Our findings suggest a need to reconsider routine ADA testing, as it does not correlate with clinical outcomes or infusion intervals. This raises questions about how to tailor maintenance therapy for MG patients stabilized with RTX.