Objective:

To determine whether extending rituximab dosing intervals to ≥12 months results in higher disease activity compared to standard intervals in persons with relapsing remitting multiple sclerosis (pwRRMS)

Background:

Extending rituximab dosing intervals beyond every 6 months lowers the risk of infections but effectiveness is unknown.

Design/Methods:

We conducted a retrospective cohort study of pwRRMS treated with ≥1 dose of rituximab from the membership of Kaiser Permanente Southern California, 2008-2022. The complete electronic health record was reviewed to obtain clinical and demographic variables.

Results:

We identified 2124 rituximab-treated pwRRMS with a median follow-up of 3.8 years (IQR 2.1-5.4). The median age at rituximab initiation was 37.0 years and 73.2% patients identified as female, 14.9% as Black, 38.4% as Hispanic. Rituximab dosing interval was extended at least once in 1579 (74.3%) patients (median extended interval 11.6 months, range 4.3-112.2, mean number of extended intervals=3, IQR 2-4). The majority of patients were relapse- and MRI disease activity-free on standard interval dosing (<q8 months) and extended (≥q8mo) interval dosing (95.05% and 95.12%, respectively). The crude incidence rate of relapse and/or asymptomatic MRI disease activity per 100-person-years (95%CI) stratified by dosing interval (in months) was as follows:  <8, 2.9 (2.3-3.5); ≥8 to <11, 1.9 (1.0-2.7); ≥11 to <15, 1.0 (0.6-1.4); ≥15 to <20, 1.8 (0.8-2.8); ≥20 to <26, 1.6 (0.4-2.8) and ≥26, 2.2 (1.4-3.1). Patients with relapses and/or asymptomatic MRI disease activity were more likely to be younger, have longer disease duration and prior MS treatment exposure at rituximab initiation compared with disease activity-free patients.

Conclusions:

The vast majority of rituximab-treated RRMS patients remained inflammatory disease-activity free (>95%) on standard and extended dosing intervals in this large, diverse population-based cohort. Taken together with previous studies, these findings suggest that treating RRMS patients with B-cell depleting agents q6 months increases the risk of adverse events without improving effectiveness.