Non-inferiority analysis of subcutaneous versus intravenous 300 mg monthly natalizumab administration: A post hoc analysis of the REFINE study.

To quantify the probability that monthly intravenous (IV) and subcutaneous (SC) natalizumab (NTZ) had similar efficacy in relapsing-remitting multiple sclerosis (RRMS), non-inferiority of efficacy of NTZ-SC versus NTZ-IV on combined MRI unique active lesions number (CUAL) was explored re-analysing the REFINE data set. Non-inferiority margins were selected equal to 25%/33%/50% fractions of the effect size of NTZ-IV versus placebo observed in the AFFIRM study. Ninety-nine RRMS were included. NTZ-SC resulted not inferior to NTZ-IV on CUAL for all margins at 2.5% significance level, and, in worst-case scenario, its effect over NTZ-IV did not exceed 3.5% (or 2.8%) of the effect of NTZ-IV versus placebo.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: F.M. discloses consulting honoraria from Novartis and Daiichi-Sankyohas. A.Mat. has no competing interests to declare that are relevant to the content of this article. A.Mar. reports speaking honoraria from Sanofi, Biogen, Janssen and Novartis; non-financial support from Biogen, Novartis, Janssen and Sanofi, outside the submitted work. L.M. reports non-financial support and speaker honoraria from Biogen, Novartis, Merck Serono, Genzyme and Teva and Viatris.