Harrold Leslie R, Litman Heather J, Connolly Sean E, Alemao Evo, Kelly Sheila, Rebello Sabrina, Hua Winnie, Kremer Joel M
Departments of Medicine and Orthopedics, University of Massachusetts, Worcester, MA, USA.
Corrona, LLC, Waltham, MA, USA.
Rheumatol Ther. 2019 Jun;6(2):217-230. doi: 10.1007/s40744-019-0149-3. Epub 2019 Mar 13.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serological biomarkers that are indicative of a poor prognosis in patients with rheumatoid arthritis (RA). The effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) with different mechanisms of action may vary, based on patients' serostatus. The aim of this study is to compare the effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFis) in patients with RA who were anti-cyclic citrullinated peptide antibody positive (anti-CCP+).
Abatacept or TNFi initiators with anti-CCP+ status (≥ 20 U/ml) at or prior to treatment initiation were identified from a large observational US cohort (1 December 2005-31 August 2016). Using propensity score matching (1:1), stratified by prior TNFi use (0, 1 and ≥ 2), effectiveness at 6 months after initiation was evaluated. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) score. Secondary outcomes included achievement of remission (CDAI ≤ 2.8), low disease activity/remission (CDAI ≤ 10), modified American College of Rheumatology 20/50/70 responses and mean change in modified Health Assessment Questionnaire score.
After propensity score matching, the baseline characteristics between 330 pairs of abatacept and TNFi initiators (biologic naïve, n = 97; TNFi experienced, n = 233) were well balanced with absolute value standardized differences of ≤ 0.1. Both overall, and in the biologic-naïve cohort, there were no significant differences in mean change in CDAI score at 6 months. However, in the TNFi-experienced cohort, there was a significantly greater improvement in CDAI score at 6 months with abatacept versus TNFi initiators (p = 0.033). Secondary outcomes showed similar trends.
Improvements in clinical disease activity were seen in anti-CCP+ abatacept and TNFi initiators. TNFi-experienced anti-CCP+ patients with RA had more improvement in disease activity with abatacept versus TNFis, whereas outcomes were similar between treatments in the overall population and in biologic-naïve patients.
ClinicalTrials.gov identifier: NCT01625650.
This study is sponsored by Corrona, LLC and funded by Bristol-Myers Squibb. Bristol-Myers Squibb funded the publication of this manuscript.
抗瓜氨酸化蛋白抗体（ACPAs）是高度特异性的血清生物标志物，提示类风湿关节炎（RA）患者预后不良。基于患者的血清学状态，作用机制不同的生物改善病情抗风湿药（bDMARDs）的疗效可能有所差异。本研究旨在比较阿巴西普与肿瘤坏死因子抑制剂（TNFis）在抗环瓜氨酸肽抗体阳性（抗CCP+）的RA患者中的疗效。
从美国一个大型观察性队列（2005年12月1日至2016年8月31日）中确定治疗开始时或之前抗CCP+状态（≥20 U/ml）的阿巴西普或TNFis起始治疗者。采用倾向评分匹配（1:1），按既往TNFis使用情况（0、1和≥2）分层，评估起始治疗后6个月的疗效。主要结局为临床疾病活动指数（CDAI）评分的平均变化。次要结局包括达到缓解（CDAI≤2.8）、低疾病活动度/缓解（CDAI≤10）、美国风湿病学会改良20/50/70反应以及改良健康评估问卷评分的平均变化。
倾向评分匹配后，330对阿巴西普和TNFis起始治疗者（初治生物制剂者，n = 97；曾使用TNFis者，n = 233）之间的基线特征平衡良好，绝对值标准化差异≤0.1。总体上以及在初治生物制剂队列中，6个月时CDAI评分的平均变化无显著差异。然而，在曾使用TNFis的队列中，6个月时阿巴西普起始治疗者的CDAI评分改善明显大于TNFis起始治疗者（p = 0.033）。次要结局显示出相似趋势。
抗CCP+的阿巴西普和TNFis起始治疗者的临床疾病活动度均有改善。曾使用TNFis的抗CCP+的RA患者使用阿巴西普比使用TNFis疾病活动度改善更大，而在总体人群和初治生物制剂患者中，两种治疗的结局相似。
ClinicalTrials.gov标识符：NCT01625650。
本研究由Corrona有限责任公司发起，百时美施贵宝公司资助。百时美施贵宝公司资助了本手稿的发表。
