Tofacitinib是一种口服Janus激酶抑制剂,用于治疗类风湿性关节炎(RA)。为了在每日一次(QD)托法替尼改释(MR)制剂的监管提交中提供其他临床证据,我们比较了开始使用MRQD制剂的患者和开始每天两次(BID)立即释放(IR)制剂的患者的实际依从性和有效性.
进行了两项非干预性队列研究。首先,在IBM®MarketScan®商业和Medicare补充美国保险索赔数据库(2016年3月-2018年10月)中,比较了新开始托法替尼MR11mgQD或IR5mgBID的RA患者的依从性和两个有效性指标.第二,使用在科罗纳美国RA登记处(2016年2月至2019年8月)收集的数据,比较了两种基于临床疾病活动指数(CDAI)的有效性指标,在托法替尼MR11mgQD和IR5mgBID之间,和来自托法替尼IR制剂的安慰剂对照临床试验的非劣效性标准。对注册数据进行了多种敏感性分析,以确保监管者在不同假设下获得一致的结果。
在每一项研究中,大约三分之二的患者开始了MR制剂.在索赔数据库研究中,在12个月内,托法替尼MR与IR的依从性改善,有效性至少相当,特别是在没有预先治疗的患者中。在注册研究中,在~6个月时,两种CDAI结局均证明了托法替尼MR与IR的非劣效性;这一发现在多重敏感性分析中具有稳健性.
这些结果证明了来自补充数据源的真实世界证据在理解临床实践中使用QD制剂的药物依从性的影响方面的价值。这些分析适用于监管考虑,作为RA患者托法替尼11mgQD与IR5mgBID可比性证据的重要组成部分。
索赔数据库研究:ClinicalTrials.gov标识符NCT04018001,回顾性注册于2019年7月12日。Corona美国RA注册研究:ClinicalTrials.gov标识符NCT04267380,回顾性注册2020年2月12日。
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.
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.
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.
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.
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.