Comparative Effectiveness of Fumarates Versus Sphingosine-1-Phosphate Receptor Modulators in Black Patients with Multiple Sclerosis

Abstract

Introduction: Multiple sclerosis (MS) is a heterogeneous disease that disproportionately impacts Black people with MS (PwMS), who experience more severe disease and higher relapse rates compared with non-Black populations. Despite widespread use of fumarates and sphingosine-1-phosphate (S1P) receptor modulators as oral disease-modifying therapies (DMTs) for relapsing MS, their comparative effectiveness in Black PwMS has not been studied. This study aims to help address this gap using real-world claims data.

Methods: This retrospective analysis using the Komodo Health Claims Database included Black PwMS. Patients were aged 18-64 years with ≥ 1 claim for MS diagnosis (International Classification of Diseases, Tenth Revision, Clinical Modification code G35) and ≥ 1 prescription claim for fumarates (dimethyl fumarate or diroximel fumarate) or an S1P receptor modulator (fingolimod, siponimod, ozanimod, or ponesimod) between January 2017 and April 2023. Outcomes included annualized relapse rate (ARR) and time to first relapse. Propensity score matching (2:1) and inverse probability weighting were used to balance baseline characteristics. Relapse events were identified using a claims-based algorithm.

Results: The analysis included 1664 Black PwMS (1231 and 433 in fumarate and S1P treatment arms, respectively). Post-index ARRs were comparable between groups (rate ratio [RR] 1.18, p = 0.423). Kaplan-Meier analyses showed similar relapse-free proportions at 24 months (72.6% and 74.7% in fumerate and S1P populations, respectively; p = 0.152). These findings were consistent in both the propensity score-matched and inverse probability weighted populations.

Conclusions: This real-world, claims-based analysis demonstrates that fumarates and S1P receptor modulators have similar effectiveness in reducing relapses among Black PwMS, with > 72% of patients in both treatment groups remaining relapse-free at 24 months. Given the underrepresentation of Black patients in MS clinical trials, these results provide valuable real-world evidence to guide treatment decisions for this population.

Keywords: African American populations; Dimethyl fumarate; Diroximel fumarate; Effectiveness; Multiple sclerosis; Sphingosine-1-phosphate.

Fig. 1

Study sample. ^a ≥1 claim with a diagnosis for MS (ICD-10 code G35). DMF Dimethyl fumarate, DMT disease-modifying therapy, DRF diroximel fumarate, ICD-10 International Classification of Diseases, Tenth Revision, FUM fumarate, MS multiple sclerosis, PwMS patients with MS, S1P sphingosine-1-phosphate receptor modulator

Fig. 2

The SMDs of baseline characteristics in the unadjusted population, the PS-matched population, and the IPW population. ARR Annualized relapse rate, DMT disease-modifying therapy, IPW inverse probability of treatment weights, MS multiple sclerosis, PS propensity score, SMD absolute standardized mean difference. Threshold ≤0.10 was considered to be well balanced [26]

Fig. 3

The ARR on FUM versus S1P. Relapses were defined as an MS-related inpatient claim with a primary diagnosis of multiple sclerosis (MS) or an outpatient MS-related diagnosis and prescription claim for an intravenous steroid, adrenocorticotropic hormone, total plasma exchange, or a high-dose oral corticosteroid ≤7 days after the outpatient visit. ARR was calculated as the total number of relapses observed divided by the total number of patient-years observed. The 95% CI was based on Poisson distribution. ARR Annualized relapse rate, CI confidence interval, FUM fumarates, IPW inverse probability of treatment weights, PS propensity score, S1P sphingosine-1-phosphate receptor modulators

Fig. 4

Time to first post-index relapse in the PS-matched population (a) and in the IPW population (b). Kaplan–Meier models were used to estimate the time to first relapse survival functions. CI Confidence interval, FUM fumarates, HR hazard ratio, IPW inverse probability of treatment weights, PS propensity score, S1P sphingosine-1-phosphate receptor modulators