Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
Efficacy and safety of extended-interval dosing of natalizumab in multiple sclerosis: a systematic review and meta-analysis with subgroup evaluation.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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Hammadeh Bara M, Sameer Sadeen, Alnajjar Mohammed, Abu-Issa Issam, Alhallaq Mohammed S, Ghazi Mustafa, Badr Ahmed, Shawawrah Mays
Аннотация
BACKGROUND: Natalizumab is effective for relapsing-remitting multiple sclerosis (RRMS) but increases the risk of progressive multifocal leukoencephalopathy (PML). Extended-interval dosing (EID) may lessen this risk by reducing drug exposure, though its efficacy and safety compared with standard-interval dosing (SID) remain unclear. This review and meta-analysis evaluates both regimens across clinical and MRI outcomes.
METHODS: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Web of Science, Cochrane Library, and ScienceDirect from inception to July 2025. Eligible studies compared extended- (5-12 weeks) and standard-interval (4 weeks) natalizumab dosing in MS. Meta-analyses used random- or fixed-effects models with results as RR or MD based on heterogeneity (I²).
RESULTS: Twenty-five studies were included. Analysis showed no significant differences between EID and SID in disability progression (MD -0.09, 95% CI: -0.46 to 0.29), or the risk of new T2 lesions (RR 1.24, 95% CI: 0.96 to 1.61). For PML incidence (RR 1.03, 95% CI: 0.29-3.60), the analysis was severely underpowered due to rare events; the wide confidence interval precludes any firm conclusion about comparative safety. However, EID was associated with a significantly higher risk of gadolinium-enhancing lesions (RR 1.35, 95% CI: 1.03-1.77). EID was associated with a borderline reduction in the risk of clinical relapse (RR 0.91, 95% CI: 0.83 to 1.00), but this finding is likely influenced by selection bias and should be considered hypothesis-generating rather than confirmatory. Subgroup analysis suggested a possible difference between intervals (P = 0.0323 for T2 lesions), but this finding is based on very sparse data, with only one subgroup (Q5-8 W) containing multiple studies and all other subgroups relying on single studies. Therefore, no definitive conclusion about optimal interval length can be drawn; the result is hypothesis-generating only.
CONCLUSION: Extended-interval dosing of natalizumab shows efficacy and safety comparable to standard dosing. Although relapse reduction was noted, this may reflect selection bias. Shorter EID intervals (5-8 weeks) appear to maintain better radiologic control, supporting EID up to 6-8 weeks as a viable option pending long-term and biomarker-guided validation.
METHODS: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Web of Science, Cochrane Library, and ScienceDirect from inception to July 2025. Eligible studies compared extended- (5-12 weeks) and standard-interval (4 weeks) natalizumab dosing in MS. Meta-analyses used random- or fixed-effects models with results as RR or MD based on heterogeneity (I²).
RESULTS: Twenty-five studies were included. Analysis showed no significant differences between EID and SID in disability progression (MD -0.09, 95% CI: -0.46 to 0.29), or the risk of new T2 lesions (RR 1.24, 95% CI: 0.96 to 1.61). For PML incidence (RR 1.03, 95% CI: 0.29-3.60), the analysis was severely underpowered due to rare events; the wide confidence interval precludes any firm conclusion about comparative safety. However, EID was associated with a significantly higher risk of gadolinium-enhancing lesions (RR 1.35, 95% CI: 1.03-1.77). EID was associated with a borderline reduction in the risk of clinical relapse (RR 0.91, 95% CI: 0.83 to 1.00), but this finding is likely influenced by selection bias and should be considered hypothesis-generating rather than confirmatory. Subgroup analysis suggested a possible difference between intervals (P = 0.0323 for T2 lesions), but this finding is based on very sparse data, with only one subgroup (Q5-8 W) containing multiple studies and all other subgroups relying on single studies. Therefore, no definitive conclusion about optimal interval length can be drawn; the result is hypothesis-generating only.
CONCLUSION: Extended-interval dosing of natalizumab shows efficacy and safety comparable to standard dosing. Although relapse reduction was noted, this may reflect selection bias. Shorter EID intervals (5-8 weeks) appear to maintain better radiologic control, supporting EID up to 6-8 weeks as a viable option pending long-term and biomarker-guided validation.