Supplementary materials: Comparative efficacy of diroximel fumarate, ozanimod and interferon beta-1a for relapsing multiple sclerosis using matching-adjusted indirect comparisons

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posted on 2024-08-19, 15:26 authored by Tammy Jiang, Mathura Shanmugasundaram, Ivan Bozin, Mark Freedman, James Lewin, Changyu Shen, Tjalf Ziemssen, Douglas L Arnold

These are peer-reviewed supplementary materials for the article 'Comparative efficacy of diroximel fumarate, ozanimod and interferon beta-1a for relapsing multiple sclerosis using matching-adjusted indirect comparisons' published in the Journal of Comparative Effectiveness Research.

Supplementary Table 1: Restrictions applied to EVOLVE-MS-1 to match inclusion and exclusion criteria used in RADIANCE.
Supplementary Table 2: Sensitivity analysis to estimate proportions of patients without Gd+ T1 lesions and new/newly enlarging T2 lesions if EVOLVE-MS-1 had a Week 104 visit.
Supplementary Table 3: Baseline characteristics before and after restriction and MAIC weighting in newly enrolled patients in EVOLVE-MS-1.
Supplementary Table 4: Comparison of outcomes after restriction and MAIC weighting in newly enrolled patients in EVOLVE-MS-1.

Aim: Diroximel fumarate (DRF), ozanimod (OZA) and interferon beta-1a (IFN) are disease-modifying therapies approved for the treatment of relapsing multiple sclerosis. No randomized trials have compared DRF versus OZA and IFN. We compared DRF versus OZA and DRF versus IFN using matching-adjusted indirect comparisons for efficacy outcomes, including annualized relapse rate (ARR), 12- and 24-week confirmed disability progression (CDP) and absence of gadolinium-enhancing (Gd+) T1 lesions and new/newly enlarging T2 lesions. Patients & methods: We used individual patient data from EVOLVE-MS-1 (NCT02634307), a 2-year, open-label, single-arm, phase III study of DRF (n = 1057) and aggregate data from RADIANCE (NCT02047734), a 2-year, double-blind, phase III study that compared OZA 1 mg once daily (n = 433) and intramuscular IFN 30 μg once weekly (n = 441). To account for cross-trial differences, the EVOLVE-MS-1 population was restricted to those who met the inclusion/exclusion criteria for RADIANCE, then weighted to match the average baseline characteristics of RADIANCE. Results: After weighting, DRF and OZA had similar ARRs (0.18 and 0.17, respectively), with a rate difference (DRF vs OZA) of 0.01 (95% confidence interval [CI]: -0.04 to 0.06). DRF had a lower ARR than IFN (0.18 and 0.28, respectively), with a rate difference (DRF vs IFN) of -0.10 (95% CI: -0.16 to -0.04) after weighting. Outcomes for 12- and 24-week CDP favored DRF versus OZA; 12-week CDP favored DRF versus IFN, but there was not strong evidence favoring DRF over IFN for 24-week CDP. Compared with OZA and IFN, DRF had higher proportions of patients without Gd+ T1 lesions and patients without new/newly enlarging T2 lesions. Conclusion: Disability progression and radiological outcomes were favorable for DRF versusOZA, although no differences were observed in ARR. Clinical and radiological outcomes generally favored DRF versus IFN. These findings may be informative for patients and clinicians considering different treatment options for MS.