Real-world persistence and benefit-risk profile of fingolimod over 36 months in Germany

Abstract

Objective: To assess the long-term real-world benefit-risk profile of fingolimod in patients with relapsing MS in Germany.

Methods: This analysis used data from the noninterventional real-world study, Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA), to assess prospectively the persistence, effectiveness, and safety of fingolimod over 36 months (±90 days) in Germany. For inclusion in the effectiveness analysis (n = 2,537), patients were required to have received fingolimod for the first time in PANGAEA, to have at least 12 months of data, and to have completed each 12-month follow-up period. For the safety analysis (n = 3,266), patients were additionally allowed to have received fingolimod before enrollment.

Results: At baseline, 94.7% of patients in the effectiveness analysis had received a previous disease-modifying therapy. After 36 months, 70.4% of patients were still receiving fingolimod. Over this period, annualized relapse rates decreased to 0.265 (95% CI: 0.244-0.286) from 1.79 (95% CI: 1.75-1.83), and mean Expanded Disability Status Scale scores remained stable (mean change from baseline: +0.049 [95% CI: -0.015 to +0.114]). In total, 16% of patients had 6-month confirmed disability improvement, 12.5% had 6-month confirmed disability worsening, and 52.4% were free from relapses and 6-month confirmed disability worsening. Adverse events (AEs) and serious AEs were experienced by up to 23.4% and 3.9% of patients, respectively, during any of the 12-month follow-up periods. The frequency and nature of AEs were in line with previous findings.

Conclusions: Using systematically collected data from PANGAEA, this analysis demonstrates the sustained effectiveness, high persistence, and manageable safety profile of fingolimod over 36 months.

Figure 1. Relapse^a outcomes during 36 months of fingolimod treatment

(A) Mean ARR during the 12-month prebaseline period before fingolimod initiation and during each 12-month follow-up period and in the overall 36-month follow-up period following fingolimod initiation. (B) Proportion of patients with relapse(s) during the 12-month prebaseline period before fingolimod initiation and during each 12-month follow-up period and in the overall 36-month follow-up period following fingolimod initiation. ^aRelapses were assessed in accordance with the clinical judgment of physicians in the real world. Relapses were not included in this analysis if they occurred within 30 days of a previous relapse that had already been included. Error bars show 95% CI. ARR = annualized relapse rate; n = number of patients. Data relating to the ARR for the 12-month prebaseline and 0–12-month periods were taken from Ziemssen T, Lang M, Tackenberg B et al. Clinical and demographic profile of patients receiving fingolimod in clinical practice in Germany and the benefit–risk profile of fingolimod after 1 year of treatment: initial results from the observational, noninterventional study PANGAEA. Neurotherapeutics 2018;15:190–199, with the permission of the copyright holders (authors).

Figure 2. Disability outcomes during 36 months of fingolimod treatment

(A) Mean change in the EDSS score during each 12-month follow-up period and in the overall 36-month follow-up period following fingolimod initiation. (B) Mean proportion of patients with 6-month confirmed disability improvement or 6-month confirmed disability worsening during each 12-month follow-up period and in the overall 36-month follow-up period following fingolimod initiation. ^aConfirmed disability improvement was assessed in accordance with the decreases in the EDSS score from baseline, with confirmation of the decrease in disability made at a visit in the absence of a relapse: a decrease of at least 1 point regardless of baseline EDSS scores. ^bConfirmed disability worsening was assessed in accordance with the increases in EDSS score from baseline, with confirmation of the increase in disability made at a visit in the absence of a relapse: a 1.5-point increase from a baseline EDSS score of 0; a 1-point increase from baseline EDSS scores of 1–5.0; and a 0.5-point increase in baseline EDSS scores of 5.5 or more. Patients for whom MS was a cause of death were considered to have confirmed disability worsening irrespective of baseline EDSS score or change in the EDSS score. Error bars show 95% CI. EDSS = Expanded Disability Status Scale; n = number of patients. Data for the 0–12-month change in the EDSS score were taken from Ziemssen T, Lang M, Tackenberg B et al. Clinical and demographic profile of patients receiving fingolimod in clinical practice in Germany and the benefit–risk profile of fingolimod after 1 year of treatment: initial results from the observational, noninterventional study PANGAEA. Neurotherapeutics 2018;15:190–199, with the permission of the copyright holders (authors).

Figure 3. Freedom from clinical disease activity during 36 months of fingolimod treatment

Mean proportion of patients who were free from relapses and 6-month confirmed disability progression during each 12-month follow-up period and in the overall 36-month follow-up period following fingolimod initiation. Error bars show 95% CI. N = number of patients. Data for the 0–12-month period were taken from Ziemssen T, Lang M, Tackenberg B et al. Clinical and demographic profile of patients receiving fingolimod in clinical practice in Germany and the benefit–risk profile of fingolimod after 1 year of treatment: initial results from the observational, noninterventional study PANGAEA. Neurotherapeutics 2018;15:190–199, with the permission of the copyright holders (authors).