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)

• Published in: Revista da Sociedade Brasileira de Medicina Tropical
• Main Authors: Lívia Pimenta Bonifácio, Eduardo Ramacciotti, Leandro Barile Agati, Fernando Crivelenti Vilar, Anna Christina Tojal da Silva, Paulo Louzada Júnior, Benedito Antônio Lopes da Fonseca, Hayala Cristina Cavenague de Souza, Caroline Candida Carvalho de Oliveira, Valéria Cristina Resende Aguiar, Carlos Augusto de Aguiar Quadros, Cesar Dusilek, Kengi Itinose, Ricardo Risson, Lucas Roberto Rivabem Ferreira, Renato Delascio Lopes, Esper Georges Kallas, Fernando Bellissimo-Rodrigues
• Format: Article in Journal/Newspaper
• Language: English
• Published: Sociedade Brasileira de Medicina Tropical (SBMT) 2023
• Subjects: COVID-19; SARS-CoV-2; Cytokine storm; Ixekizumab; Interleukin-2; Colchicine; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1590/0037-8682-0565-2022; https://doaj.org/article/4391a8037e444acb94a17755ec8515fb

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.