Comparative effectiveness of dimethyl fumarate in multiple sclerosis.

Pauline Bosco‐Lévy,Francis Guillemin,Abdelilah Abouelfath,Séverine Lignot,Elisabeth Maillart,Céline Louapre,Patrick Blin,Marc Debouverie,Pauline Diez,Régis Lassalle,Olivier Heinzlef,Cécile Droz‐Perroteau,Bruno Brochet

doi:10.1111/bcp.15071

Abstract

To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1-3.5years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61-0.86]) and TERI (0.81 [0.68-0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

Highlights

To date, disease-modifying therapies (DMTs) represent the main therapeutic strategy in RelapsingRemitting Multiple sclerosis (RRMS), to reduce the risk of relapses and delay disability progression
Interpretation: dimethyl fumarate (DMF) is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM)
Other baseline clinical characteristics were similar among patients initiating DMF, TERI or IMM: in each treatment group, around 35% of patients had a disability mainly of motor type, the pre-index annual rate of relapse (ARR) was on average 0.13, around 40% of patients had a multiple sclerosis (MS)-related hospitalization, around 55% of them had a visit to a neurologist and around 90% of them had a cerebral or spinal cord MRI

Summary

Introduction

Disease-modifying therapies (DMTs) represent the main therapeutic strategy in RelapsingRemitting Multiple sclerosis (RRMS), to reduce the risk of relapses and delay disability progression. Treatment options have broadened to include the orally administered DMTs fingolimod (FTY), which is predominantly indicated as secondline therapy in Europe, and more recently, teriflunomide (TERI) and dimethyl fumarate (DMF). All these drugs showed a significant treatment effect compared with placebo on the occurrence of relapses, disease activity and disability progression 1. Its clinical efficacy cannot be directly compared with other oral DMTs. A systematic review and meta-analysis of randomized clinical trials found that DMF significantly reduced the occurrence of relapse compared to IFNs, GA and TERI 2. Indirect comparisons studies are not sufficient to conclude for DMF superiority due to the variability of study population, and endpoint definitions

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