Two studies in one: A propensity-score-matched comparison of fingolimod versus interferons and glatiramer acetate using real-world data from the independent German studies, PANGAEA and PEARL.

Jonathan Alsop,Tjalf Ziemssen,Christian Cornelissen,Jennie Medin,Stefan Viktor Vormfelde

doi:10.1371/journal.pone.0173353

Abstract

BackgroundThis study compared outcomes following fingolimod or BRACE treatments (beta-interferons/glatiramer acetate) in patients with active MS (≥ 1 relapse in the previous year) following previous BRACE treatment.Methods and findingsPatients with active MS who previously received BRACE were identified from German prospective, observational studies, PANGAEA and PEARL. A novel methodology was developed to compare outcomes between propensity-score-matched cohorts (3:1 ratio) from the independent single-arm studies. Patients in PANGAEA (n = 1287) experienced 48% fewer relapses per year than those in PEARL (n = 429; annualized relapse rate ratio: 0.52; p < 0.001). The risk of 3-month or 6-month confirmed disability progression (CDP) was reduced in PANGAEA versus PEARL (3-month: 37% reduction; hazard ratio [HR], 0.63; p < 0.001; 6-month: 47% reduction; HR, 0.53; p < 0.001). A higher proportion of patients in PANGAEA (n = 1234) than PEARL (n = 401) were free from relapses and 3-month (65.7% vs 38.7%; p < 0.001) or 6-month (68.2% vs 39.2%; p < 0.001) CDP. The probability of confirmed disability improvement was higher in PANGAEA (n = 1163) than PEARL (n = 372; 3-month: 175% increase; HR, 2.75; p < 0.001; 6-month: 126% increase; HR, 2.26; p < 0.001). Patients in PANGAEA (n = 149) were less likely than those in PEARL (n = 307) to have taken sick leave (proportion with 0 days off work: 62.4% vs 44.6%; p = 0.0005). For change in disease severity from baseline (assessed by clinicians using the Clinical Global Impressions scale; PANGAEA, n = 1207; PEARL, n = 427), a larger proportion of patients had subjective improvement and a smaller proportion had worsening status in PANGAEA than PEARL (improvement: 28.2% vs 15.2%; worsening: 16.4% vs 30.4%; p < 0.0001).ConclusionsFingolimod appears to be more effective than BRACE in improving clinical and physician-/patient-reported outcomes in individuals with active MS.

Highlights

Multiple sclerosis (MS) is a chronic, inflammatory, degenerative disease of the central nervous system [1]
Patients with RRMS receiving fingolimod 0.5 mg were recruited into PANGAEA between April 2011 and December 2013, with the planned observational period ending in December 2018 [32]
On average, compared with patients in PEARL, those in PANGAEA had a diagnosis of MS for longer, had a slightly higher Expanded Disability Status Scale (EDSS) score and were more likely to have had multiple relapses in the previous year (56.7% vs 30.1%)

Summary

Introduction

Multiple sclerosis (MS) is a chronic, inflammatory, degenerative disease of the central nervous system [1] It is a leading cause of disability in young and middle-aged people, and affects approximately 2.3 million individuals worldwide [2]. Widespread diffuse damage starts early in the disease and often goes unnoticed [4,5,6,7] It is associated with progressive reduction in brain volume and accumulated loss of physical and cognitive function [4,5,6,7]; brain volume loss appears to be an important predictor of future disability [7]. This study compared outcomes following fingolimod or BRACE treatments (beta-interferons/glatiramer acetate) in patients with active MS (! 1 relapse in the previous year) following previous BRACE treatment

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