Long-Term Effect of Fingolimod on Disability: A Categorical Trend Analysis over 8 Years

Thursday, June 2, 2016
Exhibit Hall
Shannon Ritter, MS , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Anthony T Reder, MD , University of Chicago, Chicago, IL
Daniela Piani Meier, PhD , Novartis Pharma AG, Basel, Switzerland
Davorka Tomic, PhD , Novartis Pharma AG, Basel, Switzerland
Bruce AC Cree, MD, PhD , University of California San Francisco, San Francisco, CA
Jeremy Bright, PhD , Oxford Pharmagenesis, Tubney, United Kingdom
Terence Smith, PhD , Oxford Pharmagenesis, Tubney, United Kingdom

Background: Fingolimod reduced disability progression compared with placebo in the 2-year, phase 3 FREEDOMS trials. Long-term changes in Expanded Disability Status Scale (EDSS) score in the pooled FREEDOMS population may reveal insights into disability evolution and the impact of early, continuous treatment.

Objectives: To conduct long-term categorical trend analyses of disability evolution in patients with relapsing–remitting multiple sclerosis (RRMS) from FREEDOMS and FREEDOMS II. 

Methods: Post hoc analyses up to 96 months from baseline (BL) included patients randomized to fingolimod 0.5 mg (N=783) or placebo (N=773) in the 24-month FREEDOMS trials, those continuing or switching to fingolimod 0.5 mg in trial extensions, and those continuing fingolimod 0.5 mg in the observational LONGTERMS trial. Disability evolution was categorized: ‘minimal’ (change in EDSS score of ±0.5 points from BL if BL≤5.5, or of 0 points if BL>5.5); ‘improving’/’worsening’ (decrease/increase in EDSS score from BL of ≥1.0 point, confirmed for ≥6 months or confirmed and sustained until 24 or 96 months); or ‘fluctuating’ (changes differing from other defined patterns). ‘Stable/improving’ combined categories ‘minimal’ and ‘improving’.

Results: At 24 months, fewer patients experienced ‘worsening’ on fingolimod than on placebo (13.3% [n=90] vs 18.5% [n=118]; p=0.0095), but in both groups, most were classified as ‘minimal’ (35.6% [n=242] vs 32.6% [n=208]) or ‘fluctuating’ (37.0% [n=251] vs 32.9% [n=210]). At 96 months, there were still proportionately fewer continuous fingolimod patients than placebo-to-fingolimod switch patients ‘worsening’ (26.7% [n=36] vs 34.5% [n=40]; p=0.18). At 96 months, 55.6% (n=75) of patients on fingolimod were ‘stable/improving’, with proportionately more ‘improving’ (30.4% [n=41]) than at 24 months (14.1% [n=96]; p<0.0001), and fewer patients were in the ‘minimal’ (16.4–25.2%) or ‘fluctuating’ (17.8–18.1%) categories.

Conclusions: Over 2 years, disability changed minimally or fluctuated in patients with RRMS. After 8 years, disability in the majority of patients treated with fingolimod was stable or had improved.