Curtis Jeffrey R, Yun Huifeng, Chen Lang, Ford Stephanie S, van Hoogstraten Hubert, Fiore Stefano, Ford Kerri, Praestgaard Amy, Rehberg Markus, Choy Ernest
University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Sanofi, Bridgewater, NJ, USA.
Rheumatol Ther. 2023 Aug;10(4):1055-1072. doi: 10.1007/s40744-023-00568-8. Epub 2023 Jun 22.
Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]).
Sarilumab initiators from the ACR-RISE Registry, with ≥ 1 prescription on/after its FDA approval (2017-2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase 3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and Cohort C (characteristics matched to the phase 3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12 months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3 mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24 weeks.
Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12 months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5 mg/l) showed better response to sarilumab in rule-positive patients.
In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data.
临床试验结果可能无法推广至常规临床实践。本研究评估了托珠单抗在类风湿关节炎（RA）患者中的有效性，并测试了基于机器学习从试验数据得出的反应预测规则（基于C反应蛋白[CRP]＞12.3mg/L和血清阳性[抗环瓜氨酸肽抗体，ACPA+]）在现实世界中的适用性。
来自美国风湿病学会-类风湿关节炎改善和安全性评估（ACR-RISE）注册研究的托珠单抗起始使用者，在其获得美国食品药品监督管理局（FDA）批准后（2017 - 2020年）有≥1次处方，根据逐渐严格的标准分为三个队列：队列A（患有活动性疾病）、队列B（符合对肿瘤坏死因子抑制剂[TNFi]反应不足/不耐受的RA患者3期试验的入选标准）和队列C（特征与3期试验基线匹配）。在6个月和12个月时评估临床疾病活动指数（CDAI）和患者指数数据3的常规评估（RAPID3）的平均变化。在一个单独的队列中，根据CRP水平和血清阳性状态（ACPA和/或类风湿因子）测试预测规则；患者被分为规则阳性（CRP＞12.3mg/L且血清阳性）和规则阴性组，以比较在24周内达到CDAI低疾病活动度（LDA）/缓解和最小临床重要差异（MCID）的几率。
在托珠单抗起始使用者中（N = 2949），各队列均观察到治疗有效性，队列C在6个月和12个月时改善更明显。在预测规则队列中（N = 205），规则阳性（与规则阴性相比）患者更有可能达到LDA（优势比：1.5[0.7，3.2]）和MCID（1.1[0.5，2.4]）。敏感性分析（CRP＞5mg/L）显示规则阳性患者对托珠单抗反应更好。
在现实世界中，托珠单抗显示出治疗有效性，在最具选择性的人群中改善更明显，这与3期TNFi难治性和规则阳性RA患者情况相似。血清阳性似乎比CRP更能驱动治疗反应，尽管在常规临床实践中优化该规则需要更多数据。
