Abstract
Objective : Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study. Methods : Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment. Results : Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events. Conclusion : Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.
Keywords: COVID-19; Itolizumab; acute respiratory distress syndrome; anti-CD6; coronavirus; cytokine release syndrome; immune hyperactivation; immunotherapy.
【저자키워드】 COVID-19, coronavirus, acute respiratory distress syndrome, itolizumab, Cytokine release syndrome, immunotherapy., anti-CD6, immune hyperactivation, 【초록키워드】 Treatment, ARDS, Open-label, IL-6, Immunotherapy, outcome, immune, lymphopenia, Randomized, survival, immunomodulatory, Patient, death, patients, COVID-19 patients, mAb, immunomodulatory therapy, acute respiratory distress, supportive care, COVID-19 patient, Safe, Enrollment, FiO2, PaO2, SpO2, 95% CI, necrotic, reaction, syndrome, cytokine release, Two-arm, reduction in mortality, Complete, objective, FIVE, effective, Transient, Result, reported, evaluated, events, receiving, screened, treated, Two patient, replaced, reduction in, 【제목키워드】 Open-label, Randomized, Patient, Efficacy and safety, moderate, severe ARDS, Two-arm, evaluate,