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Research Article
12 September 2025

Matching-adjusted indirect comparisons of diroximel fumarate, ocrelizumab and interferon beta-1a for relapsing multiple sclerosis

Authors: Carrie M Hersh https://orcid.org/0000-0002-5716-5645 [email protected], Yolanda Aladro-Benito https://orcid.org/0000-0001-9459-5452, James B Lewin https://orcid.org/0000-0002-2352-9113, Changyu Shen https://orcid.org/0000-0002-4444-0943, Ivan Božin https://orcid.org/0009-0008-2205-4233, and Zhaonan Sun https://orcid.org/0000-0001-5333-4387Author Info & Affiliations
Volume 14, Number 10
https://doi.org/10.57264/cer-2025-0061
PDFFormats

Abstract

Aim: This study compares the efficacy of diroximel fumarate (DRF) with ocrelizumab (OCR) and interferon beta-1a (IFNβ-1a) for treating relapsing multiple sclerosis (MS) through matching-adjusted indirect comparisons (MAICs). Materials & methods: We used individual patient data from the EVOLVE-MS-1 (NCT02634307) study, the phase III trial of DRF (n = 1057), and group-level data from the OPERA I/II studies (NCT01247324 and NCT01412333), the 96-week, randomized, double-blind, phase III trials of OCR (n = 827) and IFNβ-1a (n = 829). EVOLVE-MS-1 data were adjusted to match the inclusion/exclusion criteria and baseline characteristics of OPERA I/II participants. Comparisons were made for annualized relapse rates (ARRs), confirmed disability progression (CDP) and radiological outcomes. Results: Baseline characteristics were balanced post-adjustment. ARR comparisons at 96 weeks showed no significant difference for DRF versus OCR (0.18 vs 0.16, p = 0.347) but favored DRF over IFNβ-1a (0.19 vs 0.29, p = 0.002). At 96 weeks, there were no significant differences in rates of 12-week or 24-week CDP between DRF and OCR (12 week: 6.4 vs 9.1%, p = 0.074; 24 week: 4.8 vs 6.9%, p = 0.14); both CDP outcomes favored DRF over IFNβ-1a (12 week: 6.5 vs 13.6%, p < 0.0001; 24 week: 4.9 vs 10.5%, p < 0.0001). The proportion of patients with gadolinium-enhancing lesions was higher for DRF versus OCR (16.4 vs 9.1%, p < 0.0001) but lower for DRF versus IFNβ-1a (15.7 vs 33.2%, p < 0.0001). The proportion of patients with new/newly enlarging T2 lesions was higher for DRF versus OCR (59.5 vs 38.7%, p < 0.0001), but there was no significant difference for DRF versus IFNβ-1a (58.4 vs 61.7%). Conclusion: While there were no significant differences in clinical outcomes (ARR, 12-week CDP and 24-week CDP) observed for DRF versus OCR, radiological outcomes indicated favorability for OCR. All outcomes favored DRF over IFNβ-1a, except from new/newly enlarging T2 lesions, which showed no significant difference.

Plain language summary

What is this article about?

This article looks at how three different multiple sclerosis (MS) treatments – diroximel fumarate (DRF), ocrelizumab (OCR) and interferon beta-1a (IFNβ-1a) – compare for people with relapsing MS. The authors applied a statistical approach to balance differences among patients in separate studies, aiming to see how well each medication reduces the number of relapses, slows disability progression and affects brain lesions seen on MRI scans.

What were the results?

DRF and OCR had similar effects on relapse rates and disability progression; however, OCR showed fewer new or active brain lesions. When compared with IFNβ-1a, DRF resulted in fewer relapses and lower rates of disability, though it did not differ much from IFNβ-1a in some types of lesions.

What do the results mean?

These findings suggest that in some cases, DRF may be a good treatment option to reduce relapses and stabilize disability. DRF also appears more effective than IFNβ-1a overall. This information can help people with MS and their healthcare providers consider the pros and cons of each treatment option, but it is important to note that these comparisons are based on indirect analyses, which have limitations. Individual patient factors and preferences should always be considered when choosing a treatment. Therefore, a personalized approach is essential when starting a new therapy for relapsing MS.

Supplementary Material

File (supplementary materials.docx)

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
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