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

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.