Providence Multiple Sclerosis Center, Providence Brain and Spine Institute, 2805 NE Glisan St., Portland, OR, 97213 USA.
Bristol Myers Squibb, 3551 Lawrenceville Rd., Princeton, NJ, 08540 USA.
Mult Scler Relat Disord. 2021 Jul;52:102972. doi: 10.1016/j.msard.2021.102972. Epub 2021 Apr 25.
A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS.
A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.
After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI.
In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.
越来越多的免疫调节疾病修正疗法可用于治疗复发型多发性硬化症（RMS）。在缺乏随机头对头试验的情况下，可以使用匹配调整的间接比较（MAIC）来调整试验间差异，并评估这些药物的比较疗效和安全性。我们使用 MAIC 方法学来间接比较奥扎那肽（OZM）和特立氟胺（TERI）在 RMS 治疗中的关键结局。
进行了系统的文献检索，以确定评估 OZM 与 TERI 疗效和安全性的临床试验。鉴于缺乏 OZM 与 TERI 的头对头试验，我们使用匹配调整的间接比较来调整潜在的治疗效果修饰剂和预后因素，同时评估确认的残疾进展（CDP）、复发和安全性结局。使用奥扎那肽的个体患者数据（SUNBEAM 和 RADIANCE 第 B 部分试验）和特立氟胺的汇总水平数据（ASCLEPIOS I/II、TOWER、OPTIMUM 和 TEMSO 试验）来评估以下结局：年化复发率（ARR）、复发患者比例、3 个月和 6 个月时的 CDP、总体不良事件（AE）、严重不良事件（SAE）和因 AE 而停药。
匹配后，OZM 和 TERI 之间的基线患者特征平衡。与 TERI 相比，OZM 显示出 ARR（比率比：0.73；95%置信区间：0.62-0.84）、复发患者比例（比值比：0.56；95%置信区间：0.44-0.70）、总体 AE（比值比：0.35；95%置信区间：0.29-0.43）、SAE（比值比：0.53；95%置信区间：0.37-0.77）和因 AE 而停药（比值比：0.14；95%置信区间：0.09-0.21）的显著改善。与 TERI 相比，OZM 在 3 个月时显示出 CDP 的统计学显著改善（风险比[HR]：0.78；95%置信区间：0.66-0.92），但在 6 个月时无显著差异（HR：0.78；95%置信区间：0.60-1.01）。
在这项 RMS 患者的间接治疗比较中，OZM 似乎比 TERI 具有更好的获益风险比。
