Long-term real-world effectiveness and safety of fingolimod over 5 years in Germany

Abstract

Objective To evaluate the 5-year real-world benefit–risk profile of fingolimod in patients with relapsing–remitting MS (RRMS) in Germany. Methods Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) is a non-interventional real-world study to prospectively assess the effectiveness and safety of fingolimod in routine clinical practice in Germany. The follow-up period comprised 5 years. Patients were included if they had been diagnosed with RRMS and had been prescribed fingolimod as part of clinical routine. There were no exclusion criteria except the contraindications for fingolimod as defined in the European label. The effectiveness and safety analysis set comprised 4032 and 4067 RRMS patients, respectively. Results At the time of the 5-year follow-up of PANGAEA, 66.57% of patients still continued fingolimod therapy. Annualized relapse rates decreased from baseline 1.5 ± 1.15 to 0.42 ± 0.734 at year 1 and 0.21 ± 0.483 at year 5, and the disability status remained stable, as demonstrated by the Expanded Disability Status Scale mean change from baseline (0.1 ± 2.51), the decrease of the Multiple Sclerosis Severity Score from 5.1 ± 2.59 at baseline to 3.9 ± 2.31 at the 60-months follow-up, and the percentage of patients with ‘no change’ in the Clinical Global Impression scale at the 60-months follow-up (78.11%). Adverse events (AE) occurring in 75.04% of patients were in line with the known safety profile of fingolimod and were mostly non-serious AE (33.62%) and non-serious adverse drug reactions (50.59%; serious AE 4.98%; serious ADR 10.82%). Conclusions PANGAEA demonstrated the sustained beneficial effectiveness and safety of fingolimod in the long-term real-world treatment of patients with RRMS.

The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary

“…Furthermore, some studies employed patients with both progressive and relapsing-remitting disease type [37]. Most of our findings corroborate the outcomes of the biggest real-life studies conducted with fingolimod so far [37,[38][39][40][41][42][43][44][45][46][47][48][49][50][51]56]. Although several papers have been published evaluating the real-world effectiveness of fingolimod, most report outcomes are capped at 2 or 3 years.…”

“…Some of them were conducted solely in a single centre [30,[39][40][41][42][43], some of them were posthoc analyses of the pivotal studies [44][45][46], some used a relatively small cohort [30,39,40,43,47,48]. Meanwhile, others have focused only on a single objective [49][50]; except a few studies [51,52], the follow-up period was surprisingly brief [43,[53][54][55] in several reports. Furthermore, some studies employed patients with both progressive and relapsing-remitting disease type [37].…”

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

“…In another placebo-controlled trial, fingolimod improved relapse-related outcomes, but showed no effect on disability worsening 6. Non-interventional real-world studies supported the beneficial effectiveness of fingolimod in terms of reduced annualised relapse rates (ARRs)7 8 and stable Expanded Disability Status Scale (EDSS) scores 7…”

Risk of cardiovascular disease in patients with multiple sclerosis treated with fingolimod compared to natalizumab: A nationwide cohort study of 2095 patients in Denmark

“…Several observational studies with follow-up durations of 2-5 years, have shown fingolimod to have an acceptable CVD safety. [7][8][9][10][11][12][13] These observational studies did, however, not include a comparator group, and CVD safety data were collected at visits in MS clinics throughout the study observation period by each patient's treating neurologist, typically in terms of seriousness, severity, duration, and link with the DMT. [7][8][9][10][11][12][13] The aim of this study was to examine CVD safety in fingolimod-treated patients including natalizumab as reference group since natalizumab and fingolimod have similar treatment indication in MS patients.…”

“…Several observational studies with follow-up durations of 2–5 years, have shown fingolimod to have an acceptable CVD safety. 7 –13 These observational studies did, however, not include a comparator group, and CVD safety data were collected at visits in MS clinics throughout the study observation period by each patient’s treating neurologist, typically in terms of seriousness, severity, duration, and link with the DMT. 7 –13…”