Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis

Abstract

Background: There is limited evidence about the optimal length of washout when switching from natalizumab to fingolimod.

Objective: To study if a washout period of 4 weeks is associated with less disease activity compared to 8 weeks.

Methods: 25 patients with Relapsing Remitting Multiple Sclerosis were included in an open label, prospective study with a follow-up of 108 weeks. The primary endpoint (PE) was defined as "time to first relapse or MRI disease activity up to week 56". In addition, a recurrent event analysis (REA) was performed up to week 108.

Results: The PE was not met (HR 0.67, 95% CI [0.22,1.97], p = 0.462). Number of relapses before stopping natalizumab was positively associated with the hazard of relapse (HR 3.91, p = 0.0117, 95% CI [1.36, 11.28]). The REA showed a reduction of the hazard to develop a relapse by 77% (HR 0.23, 95% CI [0.08, 0.69], p = 0.00854) in favor of the cohort with 4 weeks washout.

Conclusions: Our study suggests that switching from natalizumab to fingolimod with a shorter washout of 4 weeks might reduce the risk of disease reactivation after switching.

Keywords: Disease modifying drugs; Drug Switching; Fingolimod; Immunomodulation; Multiple sclerosis; Natalizumab.