Relapse Outcomes in Fingolimod-Treated Patients Previously Exposed to Natalizumab, Interferon, or Glatiramer Acetate: Results from the First Study

Background: The Fingolimod Initiation and caRdiac Safety Trial (FIRST) was a phase 3b, single-arm, open-label, multicenter, 4-month study of fingolimod 0.5 mg in patients (N=2417) with relapsing multiple sclerosis (MS) in 23 countries. In addition to treatment-naive patients, the study population included patients who had been treated with natalizumab, interferon beta (IFNβ), or glatiramer acetate (GA) prior to enrollment.

Objectives: To determine relapse outcomes with fingolimod in patients previously treated with natalizumab, IFNβ, or GA.

Methods: Post hoc analyses of data from patients who received natalizumab >6 months (n=135) and 3–6 months (n=119) prior to baseline and from patients who received IFNβ (n=1040) or GA (n=432) within 6 months prior to baseline were carried out. Pre- and on-study annualized relapse rates (ARR) and proportions of patients who were relapse free during the trial were analyzed. ARR was calculated as the total number of relapses divided by the total duration (in days) of fingolimod exposure for all patients in that group multiplied by 365.25. The ARR for the 1 year before the study was calculated as the total number of retrospectively reported relapses divided by the number of patients in the group.

Results: Prior to the study, ARR at year –1 was 1.52 in patients who discontinued natalizumab >6 months before the study, 1.08 in patients who discontinued natalizumab 3–6 months before the study, 1.13 in patients who discontinued GA before the study, and 1.01 in patients who discontinued IFNβ before the study. During 4 months of fingolimod therapy, ARR was 0.85 in the natalizumab >6 month group, 0.97 in the natalizumab 3–6 month group, 0.51 in the GA group, and 0.45 in the IFNβ group. The proportions of patients who were relapse free after 4 months of fingolimod therapy were 76.1%  in the natalizumab >6 month group, 74.8% in the natalizumab 3–6 month group, 85.9% in the GA group, and 87.3% in the IFNβ group.

Conclusions: Results of these analyses indicate that patients with relapsing MS who recently discontinued natalizumab, GA, or IFNβ had improvement in ARR with fingolimod treatment.