Sieper Joachim, Braun Jürgen, Kay Jonathan, Badalamenti Salvatore, Radin Allen R, Jiao Lixia, Fiore Stefano, Momtahen Tanya, Yancopoulos George D, Stahl Neil, Inman Robert D
Med. Department 1, Rheumatology, Charité University Medicine Berlin, Berlin, Germany.
Rheumazentrum Ruhrgebiet, Herne, Germany.
Ann Rheum Dis. 2015 Jun;74(6):1051-7. doi: 10.1136/annrheumdis-2013-204963. Epub 2014 Feb 18.
The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-α (IL-6Rα), in patients with ankylosing spondylitis (AS).
Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety.
Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints. The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred.
The ALIGN study shows that IL-6Rα blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.
ALIGN研究（NCT01061723）评估了首个全人源抗白细胞介素-6受体-α（IL-6Rα）单克隆抗体药物萨立鲁单抗在强直性脊柱炎（AS）患者中的疗效和安全性。
尽管接受了常规治疗但仍患有活动性AS的患者被随机分配至安慰剂组，或萨立鲁单抗的五种皮下给药剂量方案之一（每两周100、150或200mg，或每周100或150mg），治疗12周。主要疗效终点是在第12周达到国际脊柱关节炎协会（ASAS）20反应标准的患者百分比。次要终点包括ASAS40反应、ASAS部分缓解、AS疾病活动评分、高敏C反应蛋白（hs-CRP）值和安全性。
入组的301例患者的基线人口统计学和疾病特征在各治疗组间相似。在第12周时，安慰剂组（ASAS20 = 24.0%）与任何萨立鲁单抗剂量组之间的ASAS20反应率无统计学显著差异。与安慰剂相比，较高剂量的萨立鲁单抗使hs-CRP值显著降低。次要疗效终点无其他统计学显著差异。报告的萨立鲁单抗最常见的治疗中出现的不良事件包括感染（非严重）、中性粒细胞减少和丙氨酸转氨酶升高。未报告结核病、机会性或真菌感染或肠穿孔病例。7例患者发生治疗中出现的严重不良事件（均在萨立鲁单抗治疗组）。无死亡病例。
ALIGN研究表明，用萨立鲁单抗阻断IL-6Rα对AS并非有效治疗方法。萨立鲁单抗总体耐受性良好，安全性可控。
