Therapeutic safety and efficacy of triple-immunosuppressants versus dual-immunosuppressants in severe-to-critical COVID-19: a prospective cohort study in Bangladesh

BACKGROUND: Hyperinflammation-induced respiratory failure is a leading cause of mortality in COVID-19 infection. Immunosuppressants such as, Baricitinib and interleukin inhibitors are the drug-of-choice to suppress cytokine storm in COVID-19. Here, we compared the therapeutic safety and efficacy of triple-immunosuppressants with dual-immunosuppressants in patients with severe-to-critical COVID-19. METHODS: This study was conducted on 103 confirmed COVID-19 patients. Of 103 patients, 49 (N) and 54 (N) patients received dual-immunosuppressants (baricitinib plus two doses of secukinumab) and triple immunosuppressants (baricitinib plus single dose of tocilizumab and secukinumab) in group A and group B, respectively. Groups were compared in terms of clinical outcome, critical support-requirement, survival, re-hospitalisation, and adverse events (AEs). RESULTS: Patients in group B achieved normal blood oxygen saturation level (SpO(2)) earlier than the patients of group A [4 day (IQR: 3–12) vs 5 day (IQR: 5–14), p < .05]. The requirement of intensive care unit (ICU) and mechanical ventilation (MV) support was less in group B than group A [16.7%/28.6%, 11.1%/18.4%, respectively p < .05]]. The incidence of COVID-19 acute respiratory distress syndrome and 60-day all cause mortality was reduced in group B compared to group A [0.43 (0.19–0.98), p < .05; 0.35 (0.08–1.44), p > .05]. The 60-day re-hospitalisation rate was two-fold high in group A than group B (p = .024). Immunosuppressant-associated adverse events and secondary bacterial/fungal infections were relative high in patients of group B. CONCLUSIONS: Triple-immunosuppressants in severe-to-critical COVID-19 infection exhibited better clinical outcome; reduced ICU and MV requirement; shorter hospital stay with deceased 60-day all cause mortality and re-hospitalisation compared to dual-immunosuppressants.