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. 2025 Apr;22(3):e00554.
doi: 10.1016/j.neurot.2025.e00554. Epub 2025 Feb 20.

Extended-interval dosing of rituximab/ocrelizumab is associated with a reduced decrease in IgG levels in multiple sclerosis

Camille Rigollet  1 , Sean A Freeman  2 , Marine Perriguey  3 , Jan-Patrick Stellmann  4 , Lisa Graille-Avy  1 , Jean-Christophe Lafontaine  5 , Bruno Lemarchant  5 , Tifanie Alberto  2 , Sarah Demortière  3 , Clémence Boutiere  3 , Audrey Rico  6 , Frédéric Hilézian  3 , Pierre Durozard  7 , Jean Pelletier  6 , Adil Maarouf  6 , Hélène Zéphir  5 , Bertrand Audoin  8
Affiliations

Extended-interval dosing of rituximab/ocrelizumab is associated with a reduced decrease in IgG levels in multiple sclerosis

Camille Rigollet et al. Neurotherapeutics. 2025 Apr.

Abstract

The potential benefits of extended-interval dosing (EID) of rituximab (RTX) or ocrelizumab (OCR) in mitigating the reduction of immunoglobulin levels and decreasing the risk of infection in persons with relapsing-remitting multiple sclerosis (pwRRMS) remain largely unknown. We retrospectively analyzed two structured data collections including pwRRMS who were prescribed RTX/OCR using different interval dosing regimens, a 6-month standard-interval dosing (SD) or EID. The SD and EID cohorts included 88 and 271 pwRRMS, respectively, with a mean (SD) treatment duration of 3.5 (1.3) and 4.4 (1.5) years, and a mean (SD) interval between infusions of 6.4 (1.7) and 19.2 (11.9) months. After RTX/OCR initiation, the two cohorts did not differ in time to first relapse (p ​= ​0.83), time to first sustained accumulation of disability (p ​= ​0.98) and incidence of MRI activity (p ​= ​0.91). The time to first severe infectious event (SIE) was shorter in the SD cohort (p ​= ​0.005). The effect of treatment duration on reduction of serum IgG level was lower in the EID cohort (Estimate ​= ​0.15 ​g/L per year of follow-up, 95 ​% CI -0.06, -0.23, p ​= ​0.001). In the entire patient group, higher serum IgG levels at the last infusion were associated with a lower risk of SIE between two visits (HR ​= ​0.77 per g/L of serum IgG; 95 ​% CI: 0.66-0.91; p ​= ​0.006). This study suggests that EID of RTX/OCR may reduce the risk of serum IgG decline in pwRRMS without a loss of efficacy and may mitigate the risk of severe infections. These results must be confirmed by future randomized studies.

Keywords: Hypogammaglobulinemia; Multiple sclerosis; Ocrelizumab; Rituximab; Safety.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Treatment intervals in the two cohorts: 6-month standard-interval dosing cohort (Lille) and extended-interval dosing cohort (Marseille). (A) Change of time since last RTX/OCR infusion during the follow up; (B) Distribution of time since last RTX/OCR infusion at the two centers.
Fig. 2
Fig. 2
Kaplan-Meier Curve illustrating the time until the first relapse (A), the first sustained accumulation of disability event (B) and the first serious infectious event (C) after RTX/OCR initiation in the two cohorts: 6-month standard-interval dosing cohort (Lille) and extended-interval dosing cohort (Marseille). p-value from a log-rank test.
Fig. 3
Fig. 3
Serum IgG level in the two cohorts: 6-month standard-interval dosing cohort (Lille) and extended-interval dosing cohort (Marseille). (A) Serum IgG level evolution during the follow-up, (B) change in serum IgG levels between two visits as a grouped by the time since last RTX/OCR infusion.
See this image and copyright information in PMC

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