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

Fabrizia Mealli; Alessandra Mattei; Alice Mariottini; Luca Massacesi

doi:10.1177/13524585241238136

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

Mult Scler. 2024 Mar 13:13524585241238136. doi: 10.1177/13524585241238136. Online ahead of print.

Authors

Fabrizia Mealli^{1

2}, Alessandra Mattei^{1

2}, Alice Mariottini^{3

4}, Luca Massacesi^{3

4}

Affiliations

¹ Department of Statistics Informatics and Applications 'Giuseppe Parenti', University of Florence, Florence, Italy.
² Florence Centre for Data Science, Florence, Italy.
³ Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
⁴ Department of Neurology 2 and Tuscan Region Multiple Sclerosis Referral Centre, Careggi University Hospital, Florence, Italy.

PMID: 38481074
DOI: 10.1177/13524585241238136

Abstract

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.

Keywords: Natalizumab; disease-modifying therapies; multiple sclerosis; non-inferiority study; second-line treatment; subcutaneous.