Comparison of first-line and second-line use of fingolimod in relapsing MS: The open-label EARLIMS study

Oscar Fernández; Guillermo Izquierdo; Eduardo Aguera; Cristina Ramo; Miguel Hernandez; Diego Silva; Rob Walker; Helmut Butzkueven; Chenyu Wang; Michael Barnett; EARLIMS investigators

doi:10.1177/2055217320957358

Comparison of first-line and second-line use of fingolimod in relapsing MS: The open-label EARLIMS study

Mult Scler J Exp Transl Clin. 2020 Sep 13;6(3):2055217320957358. doi: 10.1177/2055217320957358. eCollection 2020 Jul-Sep.

Authors

Oscar Fernández^{1

2}, Guillermo Izquierdo³, Eduardo Aguera⁴, Cristina Ramo⁵, Miguel Hernandez⁶, Diego Silva⁷, Rob Walker⁸, Helmut Butzkueven⁹, Chenyu Wang^{10

11}, Michael Barnett^{10

11}; EARLIMS investigators

Affiliations

¹ Department of Neurology, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario, Málaga, Spain.
² Department of Pharmacology, Faculty of Medicine, University of Malaga, Malaga, Spain.
³ Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain.
⁴ Neurología, Hospital Universitario Reina Sofía - IMIBIC, Córdoba, Spain.
⁵ Departamento de Neurociencias, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
⁶ Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain.
⁷ Novartis Pharma AG, Basel, Switzerland.
⁸ Novartis Pharmaceuticals Australia, NSW, Australia.
⁹ MS and Neuroimmunology Unit, Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
¹⁰ Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia.
¹¹ Sydney Neuroimaging Analysis Centre, Camperdown, NSW, Australia.

Abstract

Background: Treatment of MS often begins with low-efficacy injectable disease-modifying therapy (iDMT).

Objectives: To compare the effect of fingolimod 0.5 mg/day on clinical, MRI, patient-reported, and safety outcomes, in treatment-naïve and previously treated (≥1 iDMT) patients with early MS.

Methods: EARLIMS was a multicentre, open-label, non-randomized, parallel-group phase 3 b/4 study in Australia and Spain. Patients with relapsing-remitting MS, Expanded Disability Status Scale (EDSS) score <4.0, and ≥1-5 years since diagnosis, received daily fingolimod for 48 weeks. The primary endpoint was annualized relapse rate (ARR).

Results: Of 347 patients enrolled at 51 sites (treatment-naïve, 200 [57.6%]; previously treated, 147 [42.4%]), 320 completed the study (treatment-naïve, 184 [92.0%]; previously treated, 136 [92.5%]), but the study remained underpowered (planned enrolment, n = 432). Fingolimod reduced ARR to similar levels in both treatment-naïve (mean ARR [95% confidence interval], 0.21 [0.14, 0.29]) and previously treated groups (0.30 [0.20, 0.41]; p = 0.1668). There were no new safety signals.

Conclusions: Fingolimod appeared equally effective as first- or second-line therapy in relapsing MS. There was a trend for better outcomes with fingolimod in treatment-naïve patients than in those previously treated with >1 iDMT.

Keywords: Beta-interferon; clinical trial; disease-modifying therapies; glatiramer acetate; outcome measurement; relapsing/remitting.