Background

Patients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited.

Objective

The aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population.

Methods

A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.

Results

After matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53–0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67–0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52–0.83), overall AEs (OR 0.11; 95% CI 0.08–0.16), SAEs (OR 0.27; 95% CI 0.19–0.39), and discontinuations (OR 0.11; 95% CI 0.07–0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62–1.26).

Conclusions

After adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences.

中文翻译：

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使用匹配调整的间接比较比较奥扎莫德和富马酸二甲酯治疗复发-缓解型多发性硬化症的疗效和安全性

背景

多发性硬化症 (MS) 患者经历复发和持续残疾进展。自 2004 年以来，针对 MS 的疾病缓解疗法 (DMT) 的数量大幅增长。因此，患者、医疗保健提供者和保险公司对比较疗效和安全性评估以区分治疗方案越来越感兴趣，但 DMT 之间的头对头研究是有限的。

客观的

本研究的目的是使用匹配调整间接比较 (MAIC) 来比较 DMT 奥扎尼莫德和富马酸二甲酯 (DMF) 的疗效和安全性结果，以调整研究设计和人群中的交叉试验差异。

方法

进行了系统的文献回顾，以确定评估 ozanimod 与 DMF 相比的疗效和安全性的临床研究。ozanimod 的个体患者水平数据 (IPD) 来自 SUNBEAM 和 RADIANCE Part B 试验，DMF 的总体患者水平数据 (APD) 来自 CONFIRM 和 DEFINE。MAIC 用于根据重要的基线患者特征（被认为是影响修饰符或预后因素）对 IPD 与 APD 进行加权，以平衡协变量分布以建立更同质的试验人群。一旦确定试验人群足够同质，就可以估计感兴趣的结果并将其用于产生加权 IPD 和 APD 之间的治疗效果。我们使用 MAIC 方法来比较 ozanimod 1 之间感兴趣的疗效和安全性结果。

结果

在匹配患者数据后，在接受 ozanimod 的患者和接受 DMF 的患者之间平衡了基线患者特征。与 DMF 相比，ozanimod 在 3 个月时表现出显着改善 CDP（风险比 0.67；95% 置信区间 [CI] 0.53–0.86）、ARR（比率 [RR] 0.80；95% CI 0.67–0.97）、复发患者的比例（优势比 [OR] 0.66；95% CI 0.52–0.83）、总体 AE（OR 0.11；95% CI 0.08–0.16）、SAE（OR 0.27；95% CI 0.19–0.39）和停药（OR 0.11；95 % CI 0.07–0.17)。两种药物在 6 个月时的 CDP 没有显着差异（RR 0.89；95% CI 0.62–1.26）。

结论

在调整基线患者特征后，MAIC 证明 ozanimod 1.0 mg OD 的疗效和安全性优于 DMF 240 mg BID。虽然 MAIC 不太可能产生有偏估计，而不是通过普通比较器进行的幼稚或标准间接治疗比较，但局限性包括由于未观察到的潜在混淆，因此无法解释基线差异。