Subgroup and Sensitivity Analyses of Treatment Retention in Patients Participating in the PREFERMS Study

Background: In PREFERMS, a large, randomized, prospective study, treatment retention was significantly greater with fingolimod 0.5 mg/day than with injectable disease-modifying therapies (iDMTs); many patients switched from an iDMT to fingolimod after 3–4 months. 

Objectives: To test whether the greater treatment retention rate with fingolimod than with iDMTs was robust to sensitivity and subgroup analyses.

Methods: PREFERMS was a 12-month, phase 4, open-label, active-controlled, randomized, multicenter study in patients with relapsing–remitting multiple sclerosis. At enrollment, patients were either treatment-naïve or receiving one class of iDMT (interferon or glatiramer acetate). Patients were randomized (1:1) to receive fingolimod 0.5 mg/day or a preselected iDMT. One on-study treatment switch was allowed after at least 3 months of treatment, or before if related to efficacy or safety. The primary endpoint was the proportion of patients retained on randomized treatment. A sensitivity analysis was conducted in the full analysis set (FAS) to exclude any patients who discontinued randomized treatment before 3 months for reasons other than safety or efficacy, and between days 77 and 110 (~ months 3–4) when switching for tolerability and convenience became permissible; a post hoc subgroup analysis of retention was also conducted in the FAS. Patient subgroups were defined by baseline clinical or demographic characteristics; comparisons used Cochran–Mantel–Haenszel tests adjusted for treatment naïvety.  

Results: Of 875 patients randomized (fingolimod, n=436; iDMT, n=439), 861 were included in the FAS (fingolimod, n=433; iDMT, n=428). Patient retention was significantly greater with fingolimod than with iDMTs (352 [81.3%] vs 125 [29.2%]; p<0.0001). Excluding patients as defined in the sensitivity analysis did not alter the significance of the primary endpoint (n/N [% retained]: fingolimod, 352/429 [82.1%]; iDMT, 125/298 [41.9%]; p<0.0001). Higher patient retention (p<0.01) with fingolimod than with iDMTs was also observed across subgroups stratified by race, age, disease severity, disability, employment status or treatment history. Retention across subgroups ranged from 68.4% to 91.7% in the fingolimod group, compared with 22.2% to 50.0% in the iDMT group.

Conclusions: The significantly higher treatment retention rate with fingolimod than with iDMTs seen in PREFERMS was robust to both sensitivity and subgroup analyses.