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

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.