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Increasing time between doses of natalizumab from 4.5 weeks to 6.3 weeks is not associated with reduced efficacy, and may even be associated with a lower risk for progressive multifocal leukoencephalopathy, according to a study presented at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, held October 10-12, 2018, in Berlin, Germany.
Individuals in this study were given natalizumab for a minimum of 24 weeks in 14 centers across Italy. The threshold for extended interval dosing was defined as more than 5.5 weeks. To reduce the risk for bias, the mean dose intervals were calculated using only intervals prior to the first relapse in case patients were then switched back to standard interval dosing. Noninferiority of extended interval dosing to standard interval dosing was satisfied if the annualized relapse rate’s upper 95% confidence limit among extended interval dosing patients was not higher than the mean of the standard interval dosing group’s annualized relapse rate by 0.02 relapses per year. A Mann Whitney U test was used to compare baseline characteristics between the 2 groups, while a multivariate Poisson regression model was used to compare annualized relapse rate between groups.
This study included 341 individuals with multiple sclerosis who received doses of natalizumab every 4.9 weeks (range 3.7 to 8.4). Different centers’ strategies were associated with a bimodal distribution, with 220 individuals in 12 centers showing a median of 4.5 weeks and 121 others from 2 centers showing a median of 6.2 weeks. In total, 120 individuals were given extended interval dosing (median 6.3 weeks) and 221 were given standard interval dosing. Among those with extended interval dosing, the annualized relapse rate was 0.007 (95% CI, 0.002-0.028) in follow-up, while in the standard interval dosing group it was 0.042 (95% CI, 0.026-0.067). These figures were adjusted for disease duration, Expanded Disability Status Scale score, age, relapses for 2 years before start of natalizumab, and number of prior treatments.
The study researchers concluded that “[t]here is no evidence of a reduced efficacy of natalizumab by extending the intervals between doses from a median of 4.5 to a median of 6.3 weeks. This observation confirms previous results and together with the emerging evidence of a reduced risk of [progressive multifocal leukoencephalopathy] associated to an [extended interval dosing] supports the need of a randomized study to change the standard of the natalizumab dosing schedule.”
Disclosures: Several authors report contributions from pharmaceutical companies. For a full list of author disclosures, visit the reference.
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Clerico M, Signori A, Cordioli C, et al. Extended interval dosing of natalizumab: is efficacy preserved? Presented at: 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. October 10-12, 2018; Berlin, Germany. Poster P587.