Department of Medicine, Division of Rheumatology, University of Alberta, Edmonton, AB, Canada; CARE Arthritis, Edmonton, AB, Canada.
Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany.
Lancet Rheumatol. 2022 Sep;4(9):e626-e634. doi: 10.1016/S2665-9913(22)00185-0. Epub 2022 Aug 9.
There is limited understanding regarding the inhibition of structural damage in the sacroiliac joint of patients with non-radiographic axial spondyloarthritis. This study evaluated the effect of the interleukin-17A inhibitor ixekizumab versus placebo on structural lesions in the sacroiliac joints as assessed by MRI at week 16 in patients with non-radiographic axial spondyloarthritis from the COAST-X study.
COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly allocated to placebo or double-blind ixekizumab 80 mg every 4 weeks (Q4W) or 2 weeks (Q2W), with an 80 mg or 160 mg starting dose. We report a post-hoc analysis of 266 patients with available MRI scans from baseline and week 16. MRI scans were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural score (SSS) method independently by two masked readers. Treatment comparisons used analysis of covariance based on observed cases. Correlations were evaluated among changes in SPARCC SSS for erosion, fat lesions, and backfill, and between changes in SPARCC SSS and sacroiliac joint inflammation scores and clinical measures. COAST-X was registered with ClinicalTrials.gov, NCT02757352.
Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled to the COAST-X study. 290 (96%) of 303 participants completed the week 16 visit (95 in the ixekizumab Q4W group, 98 in the ixekizumab Q2W group, and 97 in the placebo group), and MRI scans were available for 266 patients at baseline and week 16 (85 in the ixekizumab Q4W group, 91 in the ixekizumab Q2W group, and 90 in the placebo group). Changes from baseline to week 16 in mean SPARCC SSS for erosion were -0·39 for ixekizumab Q4W (p=0·003 vs placebo), -0·40 for ixekizumab Q2W (p=0·002), and 0·16 for placebo; for fat lesions: 0·16 for ixekizumab Q4W (p=0·013), 0·10 for ixekizumab Q2W (p=0·067), and -0·04 for placebo; and for backfill: 0·21 for ixekizumab Q4W (p=0·011), 0·22 for ixekizumab Q2W (p=0·006), and -0·10 for placebo. Ankylosis did not change. Effects of ixekizumab versus placebo on structural changes were most pronounced in patients with baseline inflammation in the sacroiliac joints. Changes from baseline at week 16 in erosion, fat lesions, and backfill were correlated.
Although the clinical relevance is not yet clear, patients with non-radiographic axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment.
Eli Lilly and Company.
对于非放射性轴性脊柱关节炎患者的骶髂关节结构损伤的抑制作用，人们的了解有限。本研究评估了白细胞介素-17A 抑制剂依奇珠单抗与安慰剂相比在非放射性轴性脊柱关节炎患者中的作用，这些患者来自 COAST-X 研究，在第 16 周通过 MRI 评估了骶髂关节的结构病变。
COAST-X 是一项为期 52 周、随机、双盲、安慰剂对照、平行组研究，在欧洲、亚洲、北美和南美 15 个国家的 107 个地点进行。符合条件的参与者为年龄≥18 岁的成年人，患有活动性轴性脊柱关节炎但无明确的放射性骶髂关节炎（非放射性轴性脊柱关节炎），有客观炎症迹象（通过 MRI 或 C 反应蛋白），并且对非甾体抗炎药反应不足或不耐受。患者被随机分配至安慰剂或双盲依奇珠单抗 80mg 每 4 周（Q4W）或每 2 周（Q2W）一次，起始剂量为 80mg 或 160mg。我们报告了一项 266 例基线和第 16 周有 MRI 扫描的患者的事后分析。MRI 扫描由两位盲法读者使用加拿大脊柱关节炎研究协会（SPARCC）骶髂关节结构评分（SSS）方法独立评分。基于观察到的病例，使用协方差分析比较治疗效果。评估了侵蚀、脂肪病变和填充的 SPARCC SSS 变化之间的相关性，以及 SPARCC SSS 变化与骶髂关节炎症评分和临床指标之间的相关性。COAST-X 在 ClinicalTrials.gov 上注册，注册号为 NCT02757352。
2016 年 8 月 2 日至 2018 年 1 月 29 日期间，共有 303 名患者入组 COAST-X 研究。303 名参与者中，290 名（96%）完成了第 16 周的就诊（依奇珠单抗 Q4W 组 95 名，依奇珠单抗 Q2W 组 98 名，安慰剂组 97 名），266 名患者（依奇珠单抗 Q4W 组 85 名，依奇珠单抗 Q2W 组 91 名，安慰剂组 90 名）在基线和第 16 周时均有 MRI 扫描。与基线相比，依奇珠单抗 Q4W 组、依奇珠单抗 Q2W 组和安慰剂组的平均 SPARCC SSS 侵蚀变化分别为-0.39（p=0.003）、-0.40（p=0.002）和 0.16（p=0.067），脂肪病变变化分别为 0.16（p=0.013）、0.10（p=0.067）和-0.04（p=0.583），填充变化分别为 0.21（p=0.011）、0.22（p=0.006）和-0.10（p=0.689）。强直没有变化。与安慰剂相比，依奇珠单抗对结构变化的疗效在基线时骶髂关节有炎症的患者中最为显著。第 16 周时侵蚀、脂肪病变和填充的基线变化之间存在相关性。
虽然临床相关性尚不清楚，但与安慰剂相比，接受依奇珠单抗治疗的非放射性轴性脊柱关节炎患者在第 16 周时骶髂关节的侵蚀减少，脂肪病变和填充增加，提示依奇珠单抗治疗有早期修复过程。
礼来公司。
