Rituximab in Relapsing MS: Efficacy and Safety Post-High-Efficacy DMTs

The RENEGADE study, a multicenter retrospective cohort, shows switching to rituximab rapidly stabilizes relapsing MS: annualized relapse rate (ARR) fell from 1.15 (95% CI 1.02–1.28) pre‑switch to 0.28 (95% CI 0.21–0.36) at 24 months (rate ratio 0.24; p<0.001), with corresponding reductions in MRI activity—supporting rituximab as a practical rescue option.

This was an observational, real‑world multicenter retrospective cohort of treatment‑experienced relapsing MS patients (N=320, enrolled 2015–2022).

ARR declined from a pre‑switch mean of 1.15 to 0.28 at 24 months (rate ratio 0.24, 95% CI 0.18–0.32; p<0.001), with the largest falls evident by 24 months across subgroups (prior DMT strata, denominators n=40–120). MRI outcomes paralleled clinical gains: mean new/enlarging T2 lesions dropped from 0.80 to 0.20 per patient‑year (≈75% relative reduction, 95% CI 64–82%), and contrast‑enhancing lesions fell by a similar proportion. Disability trajectories were largely stable (mean EDSS change +0.02, 95% CI −0.05–0.09); 85% of patients were classified as disability‑stable, and PIRA events were uncommon (≈3% overall in prespecified cohorts).

Across 642 patient‑years of follow‑up there were 36 adverse events in 18 patients (5.6 events per 100 patient‑years); most were mild infusion reactions. Two grade‑3 infections were recorded (CTCAE v5); most infections were judged possibly or probably treatment‑related and were managed conservatively. No progressive multifocal leukoencephalopathy (PML) cases or deaths were reported. Overall tolerability supports a favorable risk–benefit balance in this treatment‑experienced population, with routine laboratory and infection surveillance advised.

Short natalizumab washout intervals (median ≈34 days) were commonly used and may have mitigated rebound risk in this cohort. Attention to vaccination timing and recent infections is important—avoid live vaccines and check immunoglobulin status where indicated before re‑treatment. Real‑world monitoring of B‑cell repopulation and immunoglobulin levels informed retreatment intervals. Compared with other anti‑CD20 agents, rituximab’s real‑world profile aligns with class expectations for robust B‑cell depletion without clear superiority; it is a pragmatic choice when the clinical goal is rapid control of inflammatory activity.

Key Takeaways:

• RENEGADE provides real‑world evidence that switching to rituximab reduces relapses and MRI activity in patients previously on high‑efficacy DMTs.
• Safety signals were generally mild; infections predominated among adverse events, and no PML cases were observed.
• Practical sequencing considerations: short natalizumab washouts, coordinated vaccine timing, and monitoring B‑cell reconstitution and immunoglobulin levels to guide retreatment.