Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the “per protocol” population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization’s (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

摘要
背景：仍有需住院治疗的2019冠状病毒病（COVID-19）病例出现在易感人群中，凸显了新型治疗手段的重要性。该疾病的严重程度以过度炎症反应为核心病理机制，靶向该通路或具备临床应用价值。本研究旨在评估针对白细胞介素（interleukin, IL）-6、IL-17及IL-2的免疫调节治疗能否改善住院COVID-19患者的临床结局。
方法：本项多中心、开放标签、前瞻性随机对照试验在巴西开展。60例中度至重度COVID-19住院患者在标准治疗（standard of care, SOC）基础上，分别接受以下干预：IL-17抑制剂依奇珠单抗（ixekizumab）80mg皮下注射，每周1次，每4周给药1剂；低剂量IL-2（每日150万国际单位），疗程7天或直至出院；间接IL-6抑制剂秋水仙碱（colchicine）口服，初始剂量为0.5mg，每8小时1次，持续3天，后续调整为0.5mg每日2次，持续4周；或仅接受标准治疗。主要结局指标在符合方案（per protocol）人群中评估，定义为至第28天时，患者在世界卫生组织（World Health Organization, WHO）七分类序数量表上的评分较基线下降≥2分的患者比例。
结果：所有干预措施均具有安全性，各治疗组的疗效结局与标准治疗组相比无显著差异。值得注意的是，秋水仙碱组所有受试者的WHO七分类序数量表评分均下降≥2分，且未观察到患者死亡或病情恶化情况。
结论：依奇珠单抗、秋水仙碱及IL-2均被证实具有良好安全性，但用于COVID-19治疗时未展现出显著疗效。由于本研究样本量有限，对上述结果的解读需谨慎。