Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study

Abstract

Introduction: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS.

Methods: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion.

Results: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9).

Conclusions: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis.

Keywords: Disability; Disease-modifying treatment; Effectiveness; Quality of life; Radiological markers; Relapsing–remitting multiple sclerosis; Tolerability.

Fig. 1

Patient disposition. FAS full analysis set, CTS continuous treatment set, PI prescribing information compliant, RRMS relapsing–remitting multiple sclerosis. Percentages are calculated with respect to the number of patients enrolled in each case. Multiple reasons can be provided for fingolimod discontinuation and, for this reason, the response modalities are not mutually exclusive

Fig. 2

Previous disease-modifying treatments (FAS). Data correspond to the last disease-modifying treatment used before inclusion in the study. DMF dimethylfumarate, Exp experimental therapy, FGM fingolimod, GA glatiramer acetate, IFN-β interferon-β, NTZ natalizumab, OCR ocrelizumab, TFL teriflunomide; ¹Azathioprine, cyclophosphamide, methotrexate or mycophenolate mofetil. ²Laquinimod, siponimod, daclizumab, high-dose vitamin D or zaurategrast

Fig. 3

Annual relapse rate over the course of the study (FAS and CTS sets). Data are presented as mean values with their 95% confidence intervals. Light columns, full analysis set; dark columns, continuous treatment set. The numbers below the columns (N) indicate the number of patients available for analysis at each time point

Fig. 4

EDSS disability score over the course of the study (FAS set). Data are presented as a box and whisker plot. The white circles represent the mean values (with figure above), the white bars represent the median values, the grey boxes represent the interquartile ranges and the whiskers represent the extreme (minimum and maximum) values. The numbers below the columns indicate the number of patients available for analysis at each time point

Fig. 5

Radiological disease activity over the course of the study. FAS full analysis set, CTS continuous treatment set