Formerly: Biogen, Cambridge, MA 02142, USA.
Biogen, 6340, Baar, Switzerland.
J Comp Eff Res. 2024 Oct;13(10):e230161. doi: 10.57264/cer-2023-0161. Epub 2024 Aug 19.
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. 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. 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. Disability progression and radiological outcomes were favorable for DRF versus OZA, 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.
富马酸二甲酯（DRF）、奥扎莫德（OZA）和干扰素β-1a（IFN）是获批用于治疗复发型多发性硬化症的疾病修正治疗药物。目前尚无 DRF 与 OZA 和 IFN 直接比较的随机临床试验。我们使用匹配调整后的间接比较，比较了 DRF 与 OZA 和 DRF 与 IFN 的疗效结局，包括年化复发率（ARR）、12 周和 24 周确认的残疾进展（CDP）、无钆增强（Gd+）T1 病变和新/扩大 T2 病变的情况。我们使用了 EVOLVE-MS-1 研究（NCT02634307）的个体患者数据，这是一项为期 2 年的开放标签、单臂、III 期 DRF 研究（n=1057），以及 RADIANCE 研究（NCT02047734）的汇总数据，这是一项为期 2 年的双盲、III 期研究，比较了 OZA 1mg 每日一次（n=433）和肌肉内 IFN 30μg 每周一次（n=441）。为了考虑试验间的差异，将 EVOLVE-MS-1 人群限制在符合 RADIANCE 纳入/排除标准的人群中，然后进行加权以匹配 RADIANCE 的平均基线特征。加权后，DRF 和 OZA 的 ARR 相似（分别为 0.18 和 0.17），DRF 与 OZA 的差异率为 0.01（95%置信区间[CI]：-0.04 至 0.06）。DRF 的 ARR 低于 IFN（分别为 0.18 和 0.28），DRF 与 IFN 的差异率为-0.10（95%CI：-0.16 至 -0.04）。12 周和 24 周 CDP 的结果有利于 DRF 与 OZA；12 周 CDP 有利于 DRF 与 IFN，但在 24 周 CDP 方面，没有强有力的证据支持 DRF 优于 IFN。与 OZA 和 IFN 相比，DRF 有更高比例的患者无 Gd+ T1 病变和无新发/扩大 T2 病变。DRF 与 OZA 的残疾进展和影像学结局更有利，尽管在 ARR 方面没有差异。临床和影像学结局总体上有利于 DRF 与 IFN。这些发现可能为考虑多发性硬化症不同治疗方案的患者和临床医生提供信息。
