Key Results from PREFERMS: Real-World Patient Retention and Outcomes on Fingolimod versus Platform Injectable Disease-Modifying Therapies in Early Relapsing-Remitting Multiple Sclerosis (P3.115)

Objective: To examine therapeutic retention on fingolimod 0.5mg versus injectable disease-modifying therapies (iDMTs) in PREFERMS, a randomized, prospective real-world study of patients with early relapsing-remitting multiple sclerosis (RRMS). Background: Suboptimal adherence to iDMT classes is well established. PREFERMS is the first large study of treatment retention with disease modifying therapies and other outcomes in RRMS. Methods: PREFERMS was a 12-month, phase 4, open-label, active-controlled, randomized, multicenter study. At enrollment, patients were treatment-naive, or had received only one iDMT class (interferon beta or glatiramer acetate). Investigators selected an iDMT for each patient, before subjects were randomized (1:1) to fingolimod 0.5mg or the selected iDMT. One treatment switch was allowed on study, after a minimum 3 months of treatment, unless required by an adverse event. The primary endpoint was percent retained on randomized treatment. Secondary endpoints included clinical, radiographical, patient-reported outcomes, and safety assessments. Sample-size and power calculations were based on retention proportions. Results: 875 patients were randomized (fingolimod, n=436; iDMT, n=439). At baseline, mean time since diagnosis was 4.3 years and Expanded Disability Status Scale score was 2.4. In the full analysis set (n=861), 352 (81.3[percnt]) patients on fingolimod and 125 (29.2[percnt]) on iDMT completed randomized treatment (p<0.001). Despite the shorter duration of exposure to iDMTs, the annualized relapse rate was numerically lower with fingolimod (ratio, 0.70; p=0.084). There was less brain volume loss (change from baseline at month 6, 0.19[percnt] vs. 0.31[percnt], p=0.011; month 12, 0.40[percnt] vs. 0.56[percnt], p=0.076), less cortical grey matter loss (change from baseline at last assessment 0.09[percnt] vs. 0.29[percnt]; p=0.002), and treatment satisfaction was greater (Medication Satisfaction Questionnaire: p<0.001, all assessments). Safety outcomes aligned with respective labels. Conclusions: Higher therapeutic retention, improved clinical and radiographical outcomes, greater treatment satisfaction and good tolerability support front-line use of fingolimod over platform iDMTs in early RRMS. Disclosure: Dr. Cree has received personal compensation for activities with Abbvie, Biogen Idec, EMD Serono, Genzyme/sanofi aventis, Medimmune, Novartis and Teva. Dr. Cree has received research support from Acorda, EMD Serono, Hoffman La Roche, MedImmune, Novartis a Dr. Wynn has received research support from Acorda, Avanir, EMD Serono, Genzyme, GlaxoSmithKline, Hoffman-LaRoche, Novartis, Ono Pharmaceutical Co, Opexa Therapeutics, Osmotica, Pfizer, and Questcor. Dr. Mark Cascione has received research support from Novartis, Genentech, Biogen and Genzyme. Dr. Meng has received personal compensation for activities with Novartis as an employee. Dr. Schofield has received personal compensation for activities with Novartis Pharmaceuticals Corporation as an employee. Dr. Tenenbaum has received personal compensation for activities with Novartis Pharmaceutical Corporation as an employee.