Effectiveness of anti-CD20 therapies following natalizumab discontinuation: insights from a cohort study

Abstract

Background: Natalizumab (NTZ) is a highly effective multiple sclerosis (MS) treatment but carries a high risk of progressive multifocal leukoencephalopathy in JCV-positive patients. Switching to other therapies is sometimes necessary despite the risk of increasing disease activity, even with other highly effective treatments, such as anti-CD20 therapies.

Objective: To evaluate anti-CD20 therapies effectiveness after NTZ discontinuation.

Methods: A retrospective study including MS patients who switched NTZ to anti-CD20 therapies: rituximab (RTX), ocrelizumab (OCR), and ofatumumab (OFA). Demographic, clinical, and safety data were analyzed.

Results: We included 59 patients (41 female). Mean disease duration at data collection was 7,88 ± 6,62 years. The main reason for NTZ discontinuation was safety concerns related to JCV seroconversion and serum titer increase (n = 52). RTX patients had significantly longer and more active disease before transition. Comparing annualized relapse rate (ARR) and EDSS before and after switch, RTX significantly reduced ARR (0,65 vs 0,08; p = 0007) but led to a significant EDSS increase (3,65 vs 4,15; p = 0022). No significant changes were observed for OCR and OFA. ARR reduction was greater with RTX than OCR and OFA (p = 0018), though EDSS variation did not differ. Survival analysis showed no difference in time to disease activity between groups. In this cohort, 70 % of disability progression was due to progression independent of relapse activity (PIRA).

Conclusion: Anti-CD20 therapies appear to be a safe option after NTZ discontinuation, with no rebound disease and stable EDSS. PIRA was the main driver for disability progression, emphasizing the need to control smoldering disease.

Keywords: Anti-CD20; Multiple sclerosis; Natalizumab; Ocrelizumab; Ofatumumab; Rituximab.