CIRI/Rheumatology and Fraunhofer Institute for Translationale Medicine & Pharmacology (ITMP) and Cluster of Excellence Immune-Mediated Diseases (CIMD), Goethe-University, Frankfurt.
Department of Rheumatology & Hiller Research Unit, University Hospital Duesseldorf, Duesseldorf, Germany.
Rheumatology (Oxford). 2022 Jul 6;61(7):2856-2866. doi: 10.1093/rheumatology/keab784.
ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients.
Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab.
At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes.
A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes.
clinicaltrials.gov, NCT02771210.
ACHILLES 旨在证明司库奇尤单抗在治疗脊柱关节炎（SpA）患者跟腱附着点炎中的疗效。
204 例年龄≥18 岁的活动性银屑病关节炎或中轴型 SpA 且存在足跟附着点炎的患者按 1:1 随机分为司库奇尤单抗 150/300mg 或安慰剂组，治疗至 24 周，此后安慰剂组患者转为司库奇尤单抗治疗。
24 周时，更多但统计学上无显著差异（P=0.136）的司库奇尤单抗组患者报告其受累足部的跟腱附着点炎得到缓解（42.2% vs 31.4%；优势比[OR] = 1.63；95%可信区间：0.87，3.08）。基于利兹附着点炎指数，司库奇尤单抗组报告附着点炎缓解的患者比例更高（33.3% vs 23.5%；OR = 1.65；95%可信区间：0.85，3.25）。24 周时，跟腱疼痛较基线的平均变化在司库奇尤单抗组更高（-2.8 [3.0] vs -1.9 [2.7]）。司库奇尤单抗组在跟腱病变活动度和疾病活动的整体评估方面观察到更大的改善。通过局部阅片确认了所有患者在筛查时的 MRI 跟腱附着点炎。根据中央阅片，56%的患者出现骨髓水肿和/或肌腱炎；根据跟腱附着点炎 MRI 评分系统（HEMRIS）的事后分析，76%的患者存在附着点炎症表现，86%的患者存在附着点炎症和/或结构改变。
尽管临床诊断为跟腱附着点炎，但中央阅片有相当比例的患者的 MRI 未见炎症迹象，这突出表明附着点炎的临床和影像学评估之间的差异需要进一步研究。尽管 ACHILLES 未达到主要终点，但该研究报告了患者相关结局的具有临床意义的改善。
clinicaltrials.gov，NCT02771210。
