真实世界证据：为临床试验结果提供背景信息并为监管决策提供参考——每日一次托法替布缓释片与每日两次托法替布速释片治疗类风湿关节炎的比较。
Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis.
机构信息
Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, USA.
Corrona, LLC, Waltham, MA, USA.
出版信息
Adv Ther. 2021 Jan;38(1):226-248. doi: 10.1007/s12325-020-01501-z. Epub 2020 Oct 9.
INTRODUCTION
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation.
METHODS
Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM MarketScan Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions.
RESULTS
In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses.
CONCLUSION
These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA.
TRIAL REGISTRATION
Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.
简介
托法替布是一种用于治疗类风湿关节炎（RA）的口服 Janus 激酶抑制剂。为了在监管申报中提供关于改良释放（MR）每日一次（QD）托法替布制剂的额外临床证据，我们比较了开始使用 MR QD 制剂和开始使用即时释放（IR）每日两次（BID）制剂的患者之间的真实世界依从性和疗效。
方法
进行了两项非干预性队列研究。首先，在 IBM MarketScan 商业和医疗保险补充美国保险索赔数据库中（2016 年 3 月至 2018 年 10 月），比较新开始使用托法替布 MR 11mg QD 或 IR 5mg BID 的 RA 患者的依从性和两个疗效替代指标。其次，使用 Corrona 美国 RA 登记处（2016 年 2 月至 2019 年 8 月）收集的数据，比较托法替布 MR 11mg QD 和 IR 5mg BID 的两种基于临床疾病活动指数（CDAI）的疗效指标，并与托法替布 IR 制剂的安慰剂对照临床试验得出的非劣效性标准进行比较。对登记处数据进行了多次敏感性分析，以向监管机构保证在不同假设下结果的一致性。
结果
在每项研究中，约三分之二的患者开始使用 MR 制剂。在索赔数据库研究中，在 12 个月内，与 IR 相比，托法替布 MR 显示出改善的依从性和至少相当的疗效，特别是在没有先前高级治疗的患者中。在登记处研究中，托法替布 MR 与 IR 的两种 CDAI 结果均显示非劣效性，约 6 个月时；这一发现在多种敏感性分析中是稳健的。
结论
这些结果表明，来自补充数据源的真实世界证据在理解 QD 制剂在临床实践中对药物依从性的影响方面具有价值。这些分析适合作为监管考虑因素，作为托法替布 MR 11mg QD 与 IR 5mg BID 在 RA 患者中可比性的证据的重要组成部分。
试验注册
索赔数据库研究：ClinicalTrials.gov 标识符 NCT04018001，于 2019 年 7 月 12 日回顾性注册。Corrona 美国 RA 登记处研究：ClinicalTrials.gov 标识符 NCT04267380，于 2020 年 2 月 12 日回顾性注册。
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