Long-Term Effect of Immediate Versus Delayed Fingolimod Treatment in Young Adult Patients with Relapsing-Remitting Multiple Sclerosis: Pooled Analysis from the FREEDOMS/FREEDOMS II Trials

Angelo Ghezzi; Tanuja Chitnis; Annik K-Laflamme; Rolf Meinert; Dieter A Häring; Daniela Pohl

doi:10.1007/s40120-019-0146-z

Long-Term Effect of Immediate Versus Delayed Fingolimod Treatment in Young Adult Patients with Relapsing-Remitting Multiple Sclerosis: Pooled Analysis from the FREEDOMS/FREEDOMS II Trials

Neurol Ther. 2019 Dec;8(2):461-475. doi: 10.1007/s40120-019-0146-z. Epub 2019 Jul 19.

Authors

Angelo Ghezzi¹, Tanuja Chitnis², Annik K-Laflamme³, Rolf Meinert⁴, Dieter A Häring³, Daniela Pohl⁵

Affiliations

¹ Centro Studi Sclerosi Multipla, Gallarate, Italy. [email protected].
² Partners Pediatric Multiple Sclerosis Centre, Massachusetts General Hospital, Boston, MA, USA.
³ Novartis Pharma AG, Basel, Switzerland.
⁴ DATAMAP GmbH, Freiburg, Germany.
⁵ Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Abstract

Introduction: Fingolimod has demonstrated clinical and MRI benefits versus placebo/interferon β-1a in young adults with multiple sclerosis (MS). Here we report the long-term effects of fingolimod 0.5 mg on clinical and MRI outcomes in young adults with MS aged ≤ 30 years followed up for up to 8 years (96 months).

Methods: This post hoc analysis of pooled FREEDOMS/FREEDOMS II studies included patients who either received fingolimod 0.5 mg from randomization (immediate; N = 163) or switched from placebo to fingolimod at month (M) 24 (delayed; N = 147). The 6-month confirmed disability improvement [6m-CDI: based on Expanded Disability Status Scale (EDSS)], 6m-CDI-plus (6m-CDI+; EDSS, 9-Hole Peg Test, Timed 25-Foot Walk Test), 6-month confirmed disability progression (6m-CDP), time to EDSS score ≥ 4, annualized relapse rates (ARRs), new/newly enlarging T2 (neT2) lesions, and annual rate of brain volume loss (BVL) were analyzed from baseline to M24, M48, and M96. Cox regression and negative binomial regression models were used to analyze measured outcomes.

Results: At baseline, more than two-thirds of young adult patients were treatment naïve, had more than two relapses in the previous 2 years, and EDSS score < 2. From M0 to M96, a significantly higher proportion of young adult patients in the immediate group (vs. delayed group) achieved 6m-CDI (58.2% vs. 30.5%, p = 0.0206) and 6m-CDI+ (70.6% vs. 42.3%, p = 0.0149); significantly fewer patients reached 6m-CDP (20.1% vs. 34.7%, p = 0.0058) and EDSS ≥ 4 (24.1% vs. 34.1%, p = 0.0041). Up to M96, young adults in the immediate versus delayed group had lower ARRs (0.16 vs. 0.38, p < 0.0001) and a higher proportion of patients were free of neT2 lesions at M48 (31.0% vs. 5.0%, p = 0.0011).

Conclusion: In young adult patients with MS, immediate versus delayed fingolimod treatment was associated with improved disease outcomes and greater long-term benefits in both disease activity and disability progression.

Funding: Novartis Pharma AG.

Keywords: Disability; Fingolimod; Multiple sclerosis; Relapse rates; Young adults.