Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Aetion Inc., Boston, Massachusetts, USA.
Clin Pharmacol Ther. 2020 Oct;108(4):874-884. doi: 10.1002/cpt.1861. Epub 2020 May 23.
Regulators wish to understand whether real world evidence can be used for secondary indications of biologics. Using the secondary indication of adalimumab for ulcerative colitis (UC) as an example, we aimed to replicate the ULTRA-2 randomized controlled trial finding on the effectiveness of adalimumab in patients with UC using realworld data analyses. Adalimumab, a TNF-alpha receptor inhibitor initially approved for Crohn's disease, was approved for moderate to severe UC in 2012. The ULTRA-2 trial had shown improved remission against placebo in patients with UC. Using claims data (2006-2012), we conducted a cohort study of patients with UC who initiated adalimumab and compared them with (i) nonusers and (ii) new users of infliximab using propensity score matching. The coprimary end points were corticosteroid (CS) discontinuation within 8 weeks and 1 year of treatment. We computed hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 398 matched pairs of adalimumab users vs. nonusers and 326 pairs of adalimumab vs. infliximab users. Adalimumab users were 28% more likely to achieve CS-discontinuation compared with nonusers over 1 year (HR = 1.28; 95% CI 0.94-1.73). However, unlike in ULTRA-2, this effect was not observed in the first 8 weeks (HR = 0.79; 95% CI 0.65-0.97). Compared with infliximab, adalimumab initiators showed no incremental benefit over 1 year (HR = 1.08; 95% CI 0.80-1.04), but showed a 22% reduction (HR = 0.78; 95% CI 0.64-0.95) during the first 8 weeks of treatment. In summary, our results highlight opportunities and some limitations of database analysis to identify treatment effects for secondary indications.
监管机构希望了解真实世界证据是否可用于生物制剂的次要适应证。以阿达木单抗治疗溃疡性结肠炎（UC）的次要适应证为例，我们旨在使用真实世界数据分析复制阿达木单抗治疗 UC 患者的有效性在 ULTRA-2 随机对照试验中的发现。阿达木单抗是一种最初批准用于克罗恩病的 TNF-α受体抑制剂，于 2012 年批准用于中重度 UC。ULTRA-2 试验表明，与安慰剂相比，UC 患者的缓解率有所提高。使用索赔数据（2006-2012 年），我们对开始接受阿达木单抗治疗的 UC 患者进行了队列研究，并将其与（i）未使用者和（ii）英夫利昔单抗新使用者进行了倾向评分匹配。主要终点是治疗 8 周和 1 年内停用皮质类固醇（CS）。我们计算了危险比（HR）和 95%置信区间（CI）。我们确定了 398 对阿达木单抗使用者与非使用者和 326 对阿达木单抗与英夫利昔单抗使用者的匹配对。与非使用者相比，阿达木单抗使用者在 1 年内达到 CS 停药的可能性高 28%（HR=1.28；95%CI 0.94-1.73）。然而，与 ULTRA-2 不同，这种效果在 8 周内并未观察到（HR=0.79；95%CI 0.65-0.97）。与英夫利昔单抗相比，阿达木单抗的起始治疗在 1 年内没有显示出额外的获益（HR=1.08；95%CI 0.80-1.04），但在治疗的前 8 周内显示出 22%的降低（HR=0.78；95%CI 0.64-0.95）。总之，我们的结果突出了数据库分析识别次要适应证治疗效果的机会和一些局限性。
