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

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.

本数据集为发表于《比较有效性研究杂志》之文章《比较二氯甲酸二甲酯、奥赞米德及干扰素β-1a治疗复发型多发性硬化症的疗效：基于匹配调整的间接比较》的同行评审补充材料。补充表1：EVOLVE-MS-1研究中应用于匹配RADIANCE研究纳入/排除标准的限制条件。补充表2：敏感性分析，估算在EVOLVE-MS-1研究第104周访视中，无Gd+ T1病变和出现/新出现T2病变患者的比例。补充表3：EVOLVE-MS-1研究中，在限制条件和匹配调整后新招募患者的基线特征。补充表4：在EVOLVE-MS-1研究中，对限制条件和匹配调整后新招募患者的结局进行比较。研究目标：二氯甲酸二甲酯（DRF）、奥赞米德（OZA）和干扰素β-1a（IFN）均为批准用于治疗复发型多发性硬化的疾病修饰疗法。目前尚无随机试验比较DRF与OZA以及DRF与IFN。本研究通过匹配调整的间接比较法，对DRF与OZA、DRF与IFN的有效性结局进行比较，包括年化复发率（ARR）、12周和24周确认的残疾进展（CDP）以及无钆增强（Gd+）T1病变和出现/新出现T2病变。研究方法：本研究利用EVOLVE-MS-1（NCT02634307）研究中的个体患者数据（n = 1057），该研究是一项为期2年的开放标签、单臂、III期研究，以及RADIANCE（NCT02047734）研究中的汇总数据，该研究是一项为期2年的双盲、III期研究，比较了每日一次1mg的OZA（n = 433）和每周一次肌肉注射30μg的IFN（n = 441）。为考虑跨试验差异，EVOLVE-MS-1的研究人群被限制为符合RADIANCE的纳入/排除标准，然后加权以匹配RADIANCE的平均基线特征。研究结果：在加权后，DRF和OZA的ARR相似（分别为0.18和0.17），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），加权后的差异率为-0.10（95% CI：-0.16至-0.04）。12周和24周的CDP结局显示DRF优于OZA；12周的CDP结局显示DRF优于IFN，但24周的CDP没有强有力的证据表明DRF优于IFN。与OZA和IFN相比，DRF在无Gd+ T1病变和无新出现/新扩大T2病变的患者比例中更高。结论：在DRF与OZA的比较中，残疾进展和影像学结局均较佳，尽管ARR上未观察到差异。临床和影像学结局总体上倾向于DRF优于IFN。这些发现可能对考虑不同MS治疗方案的患者和医生具有参考价值。