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Meta-Analysis
. 2024 Apr;124(2):407-417.
doi: 10.1007/s13760-024-02480-6. Epub 2024 Mar 8.

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

Eslam Mohammed Rabea  1 , Mohamed Mohamed Belal  1 , Abdelrahman H Hafez  2 , Ashraf Hassan Elbanna  1 , Mahmoud Ahmed Khalifa  1 , Anas Zakarya Nourelden  2 , Nada H Mahmoud  1 , Mohamed Sayed Zaazouee  3
Affiliations
Meta-Analysis

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

Eslam Mohammed Rabea et al. Acta Neurol Belg. 2024 Apr.

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.

Keywords: EID; Extended interval dosing; Meta-analysis; Multiple sclerosis; Natalizumab; SID; Standard interval dosing.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The PRISMA flow diagram
Fig. 2
Fig. 2
A forest plot of the risk of clinical relapse
Fig. 3
Fig. 3
A forest plot of the risk of new or newly enlarging T2 hyperintense lesions
Fig. 4
Fig. 4
A forest plot of the risk of the gadolinium-enhancing lesion
Fig. 5
Fig. 5
A A forest plot of the delta EDSS before sensitivity analysis. B A forest plot of the delta EDSS after sensitivity analysis
Fig. 6
Fig. 6
A forest plot of the PML risk
See this image and copyright information in PMC

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