Depression, Fatigue and Clinical Improvements After Switch To Fingolimod

Background: Fingolimod is a once-daily, oral therapy approved for relapsing forms of multiple sclerosis (MS). Many patients with MS do not respond adequately to initial treatment with standard disease-modifying therapy (DMT), and data are needed to inform treatment switching.

Objectives: Evaluate rates of depression, fatigue, and clinical improvement in patients with relapsing MS switching to fingolimod vs standard DMT.

Methods: The study to Evaluate Patient OutComes (EPOC) is a phase 4, open-label, multicenter, 6-month study in patients with relapsing MS. Eligible patients were fingolimod naive and had received continuous treatment with interferon β [IFNβ] or glatiramer acetate [GA] for ≥6 months before study initiation. Patients were randomized 3:1 to once-daily fingolimod 0.5 mg or standard DMT (GA, intramuscular [IM] IFNβ-1a, subcutaneous [SC] IFNβ-1a, and IFNβ-1b SC). This post hoc analysis evaluated categorical data for the secondary patient-reported outcomes, Beck Depression Inventory-II (BDI-II) and Fatigue Severity Scale (FSS), and physician-assessed Clinical Global Impression of Improvement (CGI-I) at month 3 and month 6 (last observation carried forward [LOCF]). Categories were defined by clinically relevant thresholds. Differences in categorical proportions between fingolimod and standard DMT were statistically analyzed using the Cochran Mantel Haenszel Test with no adjustment for multiple comparisons.

Results: In total, 1053 patients were randomized, and 942 (fingolimod, n=714; standard DMT, n=229) completed the study. For the BDI-II, 36.2% of patients in the fingolimod group and 33.5% of patients in the standard DMT group had scores indicative of clinical depression at baseline (P=0.515), whereas the proportions for fingolimod vs standard DMT were 23.0% and 31.5% at month 3 (P=0.013) and 22.9% vs 30.6% at month 6 (LOCF; P=0.020). For the FSS, 66.5% of patients in the fingolimod group vs 66.4% of patients in the standard DMT group had scores of borderline fatigued or fatigued at baseline (P=0.866), whereas the proportions for fingolimod vs standard DMT were 60.6% vs 66.8% at month 3 (P=0.066) and 59.9% vs 67.3% at month 6 (LOCF; P=0.052). For the CGI-I, the proportion of patients with scores of very much/much/minimally improved were 45.4% for fingolimod vs 14.0% for standard DMT at month 3 (P<0.001) and 49.9% vs 13.5% at month 6 (LOCF; P<0.001).

Conclusions: In patients with relapsing MS who were candidates for therapy change, higher proportions reported themselves to be not depressed and not fatigued 3 months after switching to fingolimod vs standard DMT, with sustained benefit at 6 months (LOCF). In addition, higher proportions of patients switching to fingolimod were rated by their clinician as very much/much/minimally improved. These data demonstrate that benefits of therapy switch from standard DMT to fingolimod are perceived by patients and physicians.