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

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Relapsing-remitting multiple sclerosis (RRMS) is often treated with B-cell depleting therapies like rituximab (RTX) and ocrelizumab (OCR).
• Standard-interval dosing (SD) of these therapies can lead to reduced immunoglobulin levels and increased infection risk.
• The efficacy and safety of extended-interval dosing (EID) in RRMS are not well understood.

Purpose of the Study:

• To investigate the potential benefits of EID of RTX/OCR in mitigating immunoglobulin reduction and decreasing infection risk in persons with RRMS (pwRRMS).
• To compare the efficacy and safety outcomes between SD and EID regimens in pwRRMS.

Main Methods:

• Retrospective analysis of two cohorts of pwRRMS treated with RTX/OCR.
• Cohorts were categorized by standard-interval dosing (SD; 6-month intervals) or extended-interval dosing (EID; variable longer intervals).
• Outcomes assessed included time to first relapse, disability accumulation, MRI activity, severe infectious events (SIEs), and changes in serum immunoglobulin G (IgG) levels.

Main Results:

• EID and SD cohorts showed no significant differences in time to first relapse, sustained disability accumulation, or MRI activity.
• The SD cohort experienced a shorter time to first severe infectious event (SIE) compared to the EID cohort (p=0.005).
• EID was associated with a lower reduction in serum IgG levels over time (p=0.001), and higher IgG levels correlated with a reduced risk of SIEs (p=0.006).

Conclusions:

• Extended-interval dosing (EID) of RTX/OCR in pwRRMS appears to maintain treatment efficacy while potentially reducing the risk of severe infections.
• EID may help mitigate the decline in serum immunoglobulin G levels, which is linked to a lower risk of severe infections.
• Further confirmation through randomized controlled trials is warranted to validate these findings.