Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

Claire Meyniel,Pierre Grammond,Edgardo Cristiano,Mark Slee,Gerardo Iuliano,Vincent Van Pesch,Guillermo Izquierdo,Norbert Vella,Helmut Butzkueven,Cavit Boz,Mary Tanner,Vetere Santiago,Marc Girard,Timothy Spelman,Michael Barnett,Fraser Moore,Marcela Fiol,Joseph Herbert,Alessandra Lugaresi,François Grand’Maison,Michelle Rutherford,Roberto Bergamaschi,Eva Havrdová ,José Antonio Cabrera-Gómez ,María Trojano ,Carolyn A Young ,Tatjana Petkovska‐Boskova ,Jeannette Lechner‐Scott ,Ricardo Fernández‐Bolaños ,G Giuliani ,Carmen Adella Sîrbu ,Vilija Jokubaitis ,Celia Oreja‐Guevara

doi:10.1371/journal.pone.0038661

Abstract

ObjectivesWe conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).MethodsThe MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation.ResultsA total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.ConclusionIn this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.

Highlights

The first attack of multiple sclerosis (MS), commonly an optic neuritis, a transverse myelitis or a brainstem syndrome, is known as a clinically isolated syndrome (CIS)
CIS were included in MSBase Incident Study (MSBASIS) by their physicians and followed for a median duration of 2.7 years (IQR 1.42, 4.69)
Baseline brain magnetic resonance imaging (MRI) scans were performed a median of 68 days from CIS onset

Summary

Introduction

The first attack of multiple sclerosis (MS), commonly an optic neuritis, a transverse myelitis or a brainstem syndrome, is known as a clinically isolated syndrome (CIS). Randomised-placebo controlled studies of immunomodulatory drugs (IMDs) in patients with CIS and early relapsing-remitting MS (RRMS) report a significant decrease in relapse rate and a reduction of brain lesion accumulation, suggesting that IMD therapy should be introduced at an early stage of the disease [1,2,3,4,5,6,7]. As IMD therapies are only partially effective and are parenterally administered, treatment persistence is a major issue. It has been reported by one large study that only 55% of MS patients continue their IMD for an 18-month period [8]. No previous studies were designed to prospectively follow patients in clinical practice from disease onset to assess factors that could predict IMD discontinuation

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