Rheumazentrum Ruhrgebiet, Herne, Germany.
Ruhr-University Bochum, Bochum, Germany.
Clin Drug Investig. 2020 Mar;40(3):269-278. doi: 10.1007/s40261-020-00886-7.
Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has demonstrated low radiographic progression over 4 years in patients with ankylosing spondylitis (AS). An adalimumab (tumor necrosis factor [TNF] inhibitor) biosimilar, GP2017 (SDZ-ADL; Sandoz), has been approved by the European Medicines Agency (July 2018) for use in all same indications as adalimumab, including AS. Adalimumab has also shown low long-term radiographic progression in patients with AS. Direct comparison of radiographic progression in AS between IL-17A and TNF inhibitors has not been studied. SURPASS is the first head-to-head, Phase IIIb, randomized, biologic-controlled study in AS to compare effects of secukinumab versus SDZ-ADL on spinal radiographic progression.
Overall, 858 biologic-naïve patients with AS with elevated high-sensitivity C-reactive protein (≥ 5 mg/L) and/or at least one syndesmophyte in the cervical/lumbar spine at baseline (without total ankylosis) were randomized (1:1:1) to subcutaneous (sc) secukinumab (300 or 150 mg) or SDZ-ADL (40 mg). Secukinumab will be administered at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 100. SDZ-ADL will be administered every 2 weeks from baseline until week 102. Patients and investigators will be unblinded to drug but blinded to secukinumab doses. Spinal X-rays will be obtained at baseline, and weeks 52 and 104, sacroiliac joint (SIJ) X-rays at baseline and week 104, and magnetic resonance imaging (MRI) of SIJs and spine at baseline, weeks 16, 52, and 104. The primary endpoint is to demonstrate superiority of secukinumab (300 or 150 mg) treatment versus SDZ-ADL regarding proportion of patients with no radiographic progression (change from baseline in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤ 0.5) at week 104. Secondary endpoints include change from baseline in mSASSS, proportion of patients with syndesmophyte at baseline who develop no new syndesmophytes, reduction of osteitis on MRI of SIJs and spine (Berlin method). Assessment of SpondyloArthritis International Society (ASAS) 20/40 responses, ASAS partial remission, and AS Disease Activity Score (ASDAS) inactive disease (ASDAS < 1.3) in secukinumab- versus SDZ-ADL-treated patients at week 104.
This is the first study designed to evaluate superiority of an IL-17A inhibitor, secukinumab, over a TNF inhibitor, SDZ-ADL, in reducing spinal radiographic progression in AS.
ClinicalTrials.gov, NCT03259074.
司库奇尤单抗是一种抗白细胞介素（IL）-17A 的单克隆抗体，在患有强直性脊柱炎（AS）的患者中，其在 4 年内的放射学进展较低。阿达木单抗（肿瘤坏死因子 [TNF] 抑制剂）的一种生物类似药，GP2017（SDZ-ADL；山德士）已获欧洲药品管理局批准（2018 年 7 月），可用于阿达木单抗的所有相同适应证，包括 AS。阿达木单抗在 AS 患者中也显示出长期放射学进展较低。IL-17A 和 TNF 抑制剂在 AS 中的放射学进展的直接比较尚未研究。SURPASS 是第一项头对头、三期 b 期、随机、生物对照研究，旨在比较司库奇尤单抗与 SDZ-ADL 对 AS 脊柱放射学进展的影响。
共有 858 名生物初治的 AS 患者，基线时（无完全强直）血清高敏 C 反应蛋白（hsCRP）升高（≥5mg/L）和/或颈椎/腰椎有至少一个骨桥，被随机（1:1:1）分配至皮下（sc）司库奇尤单抗（300 或 150mg）或 SDZ-ADL（40mg）。司库奇尤单抗将在基线时、第 1、2、3 和 4 周以及第 100 周时进行给药，然后每 4 周给药一次，直到第 100 周。SDZ-ADL 将从基线开始每 2 周给药一次，直到第 102 周。患者和研究者将对药物保持盲态，但对司库奇尤单抗剂量保持开放。基线时和第 52 和 104 周时拍摄脊柱 X 射线，基线和第 104 周时拍摄骶髂关节（SIJ）X 射线，基线、第 16、52 和 104 周时拍摄 SIJ 和脊柱的磁共振成像（MRI）。主要终点是证明司库奇尤单抗（300 或 150mg）治疗与 SDZ-ADL 相比，在第 104 周时无放射学进展（改良 Stoke 强直性脊柱炎脊柱评分[mSASSS]较基线的变化≤0.5）的患者比例具有优越性。次要终点包括 mSASSS 较基线的变化、基线时有骨桥的患者中新骨桥形成的比例、SIJ 和脊柱 MRI 上骨炎的减少（柏林方法）。在第 104 周时评估司库奇尤单抗与 SDZ-ADL 治疗患者的强直性脊柱炎国际协会（ASAS）20/40 反应、ASAS 部分缓解和 AS 疾病活动度评分（ASDAS）无疾病活动（ASDAS<1.3）。
这是第一项旨在评估 IL-17A 抑制剂司库奇尤单抗与 TNF 抑制剂 SDZ-ADL 相比，在降低 AS 脊柱放射学进展方面的优越性的研究。
ClinicalTrials.gov，NCT03259074。
