Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review

Justin D Brown; Benjamin T Muston; Jennifer Massey

doi:10.1016/j.msard.2024.105605

Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review

Mult Scler Relat Disord. 2024 Jun:86:105605. doi: 10.1016/j.msard.2024.105605. Epub 2024 Apr 19.

Authors

Justin D Brown¹, Benjamin T Muston², Jennifer Massey³

Affiliations

¹ The University of Notre Dame, Sydney, Australia. Electronic address: justin.brown@health.nsw.gov.au.
² Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; The Collaborative Research Group (CORE), Sydney, Australia.
³ Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Neurology Department, St Vincent's Hospital Sydney, Australia.

PMID: 38640586
DOI: 10.1016/j.msard.2024.105605

Abstract

Background: Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established.

Methods: In accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included.

Results: The overall incidence of clinical relapse during washout periods ranging from 4.4-10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02-0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %.

Conclusions: This systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.

Keywords: CD20; Multiple sclerosis; Natalizumab; Ocrelizumab; PML; Rituximab.

Publication types

Systematic Review

MeSH terms

Antigens, CD20 / immunology
Drug Substitution
Humans
Immunologic Factors* / administration & dosage
Immunologic Factors* / adverse effects
Immunologic Factors* / pharmacology
Leukoencephalopathy, Progressive Multifocal / chemically induced
Leukoencephalopathy, Progressive Multifocal / immunology
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / immunology
Natalizumab* / administration & dosage
Natalizumab* / adverse effects
Natalizumab* / therapeutic use

Substances

Natalizumab
Immunologic Factors
Antigens, CD20