Division of Rheumatology, Department of Medicine, Centre for Prognosis Studies in The Rheumatic Diseases, University of Toronto, Krembil Research Institute, Toronto Western Hospital, 399 Bathurst St. 1E-410B, Toronto, Ontario, M5T 2S8, Canada.
Psoriatic Arthritis Program, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Arthritis Res Ther. 2019 Jan 29;21(1):38. doi: 10.1186/s13075-019-1831-0.
Ixekizumab improves signs/symptoms of psoriatic arthritis (PsA). We present an integrated analysis of baseline disease burden and post-baseline outcomes in ixekizumab-treated patients with enthesitis or dactylitis.
Data from SPIRIT-P1 and SPIRIT-P2 were integrated. Patients with PsA were randomized to 80-mg ixekizumab every 4 weeks (IXEQ4W) or 2 weeks (IXEQ2W), after a 160-mg starting dose, or to placebo. Inadequate responders at week 16 received rescue therapy. Among patients with baseline enthesitis (Leeds Enthesitis Index [LEI] > 0) or dactylitis (Leeds Dactylitis Index-Basic [LDI-B] > 0), baseline characteristics and disease burden were reported. At week 24, LEI and LDI-B (percentage of patients with resolution [LEI = 0, LDI-B = 0]) were assessed. In pooled treatment groups, the impact of enthesitis or dactylitis resolution on health-related quality of life (HRQoL) (EuroQol-5 Dimensions Visual Analogue Scale [EQ-5D VAS]), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and pain was assessed.
The integrated analysis set comprised 679 patients; of these, 60% (n = 403 of 675) had baseline enthesitis (LEI > 0) and 23% (n = 155 of 676) had baseline dactylitis (LDI > 0). At week 24, ixekizumab-treated patients experienced significantly more resolution than placebo of enthesitis (39% IXEQ4W, 35% IXEQ2W, 21% placebo) and dactylitis (78% IXEQ4W, 65% IXEQ2W, 24% placebo). Furthermore, at entheseal points measured by the LEI, ixekizumab-treated patients had significantly higher resolution of enthesitis compared to placebo. At week 24, among all placebo- and ixekizumab-treated patients, resolution of enthesitis was associated with improvements in function and HRQoL whereas dactylitis resolution was associated with more limited improvements. The least squares mean HAQ-DI improvements from baseline were - 0.44 and - 0.25 for patients who did/did not resolve enthesitis, and - 0.41 and - 0.31 for patients who did/did not resolve dactylitis. EQ-5D VAS improvements were 12.3 and 5.8 for patients who did/did not resolve enthesitis, and 10.8 and 9.8 for patients who did/did not resolve dactylitis.
Among patients with pre-existing enthesitis or dactylitis, IXEQ2W- and IXEQ4W-treatment resulted in significant improvements in enthesitis and dactylitis. Enthesitis resolution was associated with improvements in patients' function, pain, and HRQoL.
ClinicalTrials.gov, NCT01695239 , registered on September 25, 2012, and NCT02349295 , registered on October 10, 2014.
依奇珠单抗可改善银屑病关节炎（PsA）的体征/症状。我们报告了依奇珠单抗治疗附着点炎或指（趾）炎患者的基线疾病负担和基线后结局的综合分析结果。
整合了 SPIRIT-P1 和 SPIRIT-P2 的数据。接受 160mg 起始剂量治疗后，患者被随机分配至每 4 周（IXEQ4W）或每 2 周（IXEQ2W）接受 80mg 依奇珠单抗治疗，或接受安慰剂治疗。治疗 16 周后应答不足的患者接受解救治疗。基线时存在附着点炎（利兹附着点炎指数 [LEI]＞0）或指（趾）炎（利兹指（趾）炎指数-基础 [LDI-B]＞0）的患者报告基线特征和疾病负担。在第 24 周时，评估 LEI 和 LDI-B（缓解的患者比例 [LEI=0，LDI-B=0]）。在合并治疗组中，评估附着点炎或指（趾）炎缓解对健康相关生活质量（EuroQol-5 维度视觉模拟量表 [EQ-5D VAS]）、身体机能（健康评估问卷-残疾指数 [HAQ-DI]）和疼痛的影响。
整合分析集包含 679 例患者；其中，60%（n=675 例中的 403 例）存在基线附着点炎（LEI＞0），23%（n=676 例中的 155 例）存在基线指（趾）炎（LDI＞0）。在第 24 周时，与安慰剂相比，依奇珠单抗治疗患者附着点炎（39%IXEQ4W、35%IXEQ2W、21%安慰剂）和指（趾）炎（78%IXEQ4W、65%IXEQ2W、24%安慰剂）的缓解比例显著更高。此外，根据 LEI 测量的附着点处，与安慰剂相比，依奇珠单抗治疗患者附着点炎的缓解比例更高。在第 24 周时，在所有安慰剂和依奇珠单抗治疗患者中，附着点炎的缓解与功能和 HRQoL 的改善相关，而指（趾）炎的缓解与更有限的改善相关。从基线到第 24 周，与未缓解附着点炎的患者相比，缓解附着点炎的患者的 HAQ-DI 平均最小平方差改善分别为-0.44 和-0.25，缓解指（趾）炎的患者的 HAQ-DI 平均最小平方差改善分别为-0.41 和-0.31。与未缓解指（趾）炎的患者相比，缓解指（趾）炎的患者的 EQ-5D VAS 改善分别为 12.3 和 5.8，缓解附着点炎的患者的 EQ-5D VAS 改善分别为 10.8 和 9.8。
在存在基线附着点炎或指（趾）炎的患者中，IXEQ2W 和 IXEQ4W 治疗可显著改善附着点炎和指（趾）炎。附着点炎的缓解与患者的功能、疼痛和 HRQoL 的改善相关。
ClinicalTrials.gov，NCT01695239，于 2012 年 9 月 25 日注册；NCT02349295，于 2014 年 10 月 10 日注册。
