Extended-Interval Dosing of Natalizumab Efficacy in Retrospective Propensity Score Analysis of Real-World Data

Using propensity score analysis in which individuals who had extended-interval dosing (EID) after at least 1 year of standard-interval dosing (SID) of natalizumab (Tysabri; Biogen, Cambridge, MA) were matched with individuals treated with standard-interval dosing (SID) for comparison of outcomes. Matching used exact infusion dates, physician-intended dosing frequency, and dates of deliberate dosing frequency change. Individuals treated with EID had comparable annualized relapse rates (0.231 [95% CI: 0.145-0.367 vs 0.254 [95% CI: 0.160-0.402]; P = 0.774) or risk of relapse (hazard ratio 1.021 [95% CI: 0.583-1.789]; P = .940) compared with those treated with SID.

Retrospective safety analysis has suggested that EID confers a lower risk of progressive multifocal leukoencephalopathy (PML). Frequency of EID is a 300-mg infusion every 6 weeks on average, and SID is 300-mg infusion every 4 weeks.

A total of 135 pairs of EID and SID patients were included in this analysis and demographic and disease characteristics were well balanced between groups (standard differences ≤ .033). Mean treatment duration was 4.4 years in both groups. There was no difference in ARR or risk of relapse between patient groups. 

These data were presented at the Congress of the European Committee on Treatment and Research in Multiple Sclerosis in Stockholm, Sweden September 11-13, 2019. Data was obtained from the Tysabri Observational Program. Treatment duration-matched EID and SID patients (199 pairs) were compared by propensity score matching (PSM) using age, sex, Expanded Disability Status Scale (EDSS) score, time from MS onset, natalizumab exposure duration, and relapse activity (both before natalizumab and on SID before switching) as covariates. Negative binomial model-estimated annualized relapse rate (ARR) and Kaplan-Meier-estimated risk of relapse were compared for PSM-matched EID patients during the post-switch follow-up period and SID patients during the exposure-matched follow-up period.