Effect of fingolimod versus interferon-beta1a on no evidence of disease activity or worsening (NEDA-4) in the TRANSFORMS study (P4.001)

OBJECTIVE: To compare effects of oral fingolimod vs. intramuscular interferon beta-1a (IFN) in achieving no evidence of disease activity or worsening status (NEDA-4) in patients with relapsing-remitting multiple sclerosis (RRMS) in the TRANSFORMS study. BACKGROUND: Brain volume loss (BVL) is accelerated in (MS), is associated with both focal and diffuse CNS damage, and is independently predictive of long-term disability. NEDA is used to capture MS treatment effects and has usually included 3 measures, addressing mainly focal damage: MRI lesions, relapses, and disability progression. Recent analyses of placebo-controlled FREEDOMS/FREEDOMS II trial data have shown that adding BVL to NEDA may result in a more demanding but also more comprehensive and balanced measure of focal and diffuse damage as depicted by both MRI and clinical outcomes. DESIGN/METHODS: In this post-hoc analysis of the one-year, double-blind, randomized, phase III TRANSFORMS study, we used data from the fingolimod 0.5 mg daily (n=431) and IFN 30 μg weekly (n=435) groups. NEDA-4 was defined as an absence of confirmed relapses, new/enlarging T2 lesions, 6-month confirmed disability progression (CDP) and BVL (annual percent brain volume change [PBVC] of >-0.4[percnt]). 3-month CDP and additional PBVC cut-offs representing mean BVL rates in healthy adults (0.2[percnt]), MS patients (0.6[percnt]), or accelerated BVL (1.2[percnt]) were also tested. Odds ratios (OR) were calculated for differences between fingolimod- and IFN-treated groups. RESULTS: Data were available for 425 fingolimod- and 418 IFN-treated patients. Significantly more fingolimod- than IFN-treated patients achieved NEDA-4 status: 27.9[percnt] vs. 16.7[percnt] (OR:1.93; 95[percnt] CI: 1.36-2.73; p=0.0002). Results were similar for other PBVC cut-offs: (>-0.2[percnt]): 20.2[percnt] vs 11.5[percnt]; 1.94; 1.30-2.90, p=0.0011; (>-0.6[percnt]): 34.6[percnt] vs 20.4[percnt]; 2.06; 1.49-2.86, p -1.2[percnt]): 40.8[percnt] vs 26.4[percnt]; 1.92; 1.42-2.60; p<0.0001. CONCLUSION: Fingolimod-treated patients had twice the odds of achieving NEDA-4 status over 1 year as patients treated with IFN. Study supported by Novartis Pharma AG Disclosure: Dr. Montalban has received personal compensation for activities with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall. Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly, Novartis, and Vaccinex as a consultant and/or speaker. Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Sanofi, Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, Synthon BV, and Janssen Research as a consultant. Dr. Khatri has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme, Novartis, Pfizer Inc., EDM Serono, Terumo, Corp., and Teva. Dr. Hartung has holds stock and/or stock options from Opexa Therapeutics. Dr. Ritter has received personal compensation for activities with Novartis as an employee. Dr. Meier has received personal compensation for activities with Novartis as an employee. Dr. Tomic has received personal compensation for activities with Novartis as an employee. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals.