Table_2_Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort.docx

IntroductionIxekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting.
MethodsThis retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized.
ResultsAmong the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was −1.2 (5.5) and −1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points.
ConclusionTreatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.

引言
依奇珠单抗(ixekizumab)在银屑病关节炎(psoriatic arthritis, PsA)患者的关键性临床试验中已被证实具有疗效，无论这些患者是未接受过生物制剂治疗的初治人群，还是既往对生物制剂应答不佳或不耐受的人群；然而目前关于依奇珠单抗在常规临床实践中的有效性信息仍十分有限。本研究旨在真实世界环境中，探究依奇珠单抗治疗银屑病关节炎在6个月和12个月随访周期内的临床有效性。

方法
本回顾性队列研究纳入了来自OM1 PremiOMTM PsA数据集的初始接受依奇珠单抗治疗的患者，该数据集包含超过50000例患者的理赔数据与电子病历(electronic medical record, EMR)数据。研究对6个月和12个月时的肌肉骨骼结局指标进行了汇总分析，包括压痛与肿胀关节计数、患者报告的疼痛评分，以及采用临床疾病活动指数(Clinical Disease Activity Index, CDAI)和患者常规评估指数3(Routine Assessment of Patient Index Data 3, RAPID3)评估的医师与患者整体评估情况。
针对RAPID3评分、CDAI评分及其各组成指标，本研究采用多变量回归分析进行校正，校正变量包括年龄、性别与基线值。研究结果按生物改善病情抗风湿药(biologic disease-modifying antirheumatic drug, bDMARD)治疗状态（初治 vs 经治）以及单药治疗状态（单药治疗 vs 联合传统合成改善病情抗风湿药(conventional synthetic DMARDs)治疗）进行分层。此外，研究还汇总了由医师整体评估、患者整体评估及患者报告疼痛评分组成的3项复合评分的变化情况。

结果
在纳入的1812例接受依奇珠单抗治疗的患者中，84%曾接受过bDMARD治疗，82%为单药治疗使用者。所有结局指标在6个月和12个月时均得到改善。对于RAPID3评分，6个月和12个月时的平均（标准差）变化值分别为-1.2（5.5）和-1.2（5.9）。在校正后的分析中，全部患者、经治bDMARD患者以及单药治疗患者的CDAI评分及其所有组成指标从基线至6个月和12个月时均出现了具有统计学意义的平均变化。在两个时间点，患者的3项复合评分均得到改善。

结论
依奇珠单抗治疗与肌肉骨骼疾病活动度及患者报告结局(patient-reported outcomes, PROs)的改善相关，这一点通过多项结局指标得以证实。未来的研究应采用银屑病关节炎特异性终点指标，在真实世界环境中评估依奇珠单抗在银屑病关节炎所有领域的临床有效性。