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Acta Neurologica Belgica
Published in: Acta Neurologica Belgica 2/2024

Open Access 08-03-2024 | Natalizumab | Review article

Safety and efficacy of extended versus standard interval dosing of natalizumab in multiple sclerosis patients: a systematic review and meta-analysis

Authors: Eslam Mohammed Rabea, Mohamed Mohamed Belal, Abdelrahman H. Hafez, Ashraf Hassan Elbanna, Mahmoud Ahmed Khalifa, Anas Zakarya Nourelden, Nada H. Mahmoud, Mohamed Sayed Zaazouee

Published in: Acta Neurologica Belgica | Issue 2/2024

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Abstract

Background

Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS, has been explored for its off-label extended interval dosing (EID), suggesting a potential reduction in the risk of progressive multifocal leukoencephalopathy (PML) compared to standard interval dosing (SID). Our objective was to assess the efficacy and safety of EID in comparison to SID for natalizumab treatment in patients with MS.

Methods

We searched PubMed, Embase, WOS, Scopus, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library. Our assessed outcomes were clinical relapses, MRI activity, change in expanded disability status scale [EDSS], and the risk of PML. The EID group was defined as 5 to 8 weeks [EID (Q5-8W)]. The analysis was conducted using RevMan ver. 5.4. The effect estimates were presented as a risk ratio [RR] or mean difference with 95% confidence intervals [CI] using SID group as the reference for comparisons.

Results

Fourteen studies met our inclusion criteria: 2 RCTs, 1 switched single-arm trial, and 12 observational studies. No significant differences were found in all efficacy outcomes of interest. Risk of clinical relapses [RR = 0.90, (95%CI 0.80, 1.02)], risk of new or newly enlarging T2 hyperintense MRI lesions [RR = 0.78, (95%CI 0.59, 1.04)], risk gadolinium enhancing lesions [RR = 1.30, (95%CI 0.98, 1.72)], change in EDSS [MD = 0.09 (95%CI − 0.57, 0.76)], risk of PML [RR = 1.09, 95%CI (0.24, 4.94)].

Conclusion

In summary, our meta-analysis indicates that natalizumab maintains its effectiveness under extended interval dosing [up to 8 weeks], presenting comparable risks for clinical relapses, MRI lesions, EDSS, and PML. Caution is advised given study limitations and heterogeneity. Robust conclusions necessitate well-designed high-quality prospective studies.
Appendix
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Metadata
Title
Safety and efficacy of extended versus standard interval dosing of natalizumab in multiple sclerosis patients: a systematic review and meta-analysis
Authors
Eslam Mohammed Rabea
Mohamed Mohamed Belal
Abdelrahman H. Hafez
Ashraf Hassan Elbanna
Mahmoud Ahmed Khalifa
Anas Zakarya Nourelden
Nada H. Mahmoud
Mohamed Sayed Zaazouee
Publication date
08-03-2024
Publisher
Springer International Publishing
Published in
Acta Neurologica Belgica / Issue 2/2024
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-024-02480-6

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