ABSTRACT
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 (SpO2) 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.
Subject(s)
COVID-19 Drug Treatment , Bangladesh , Humans , Immunosuppressive Agents/adverse effects , Prospective Studies , SARS-CoV-2 , Treatment OutcomeSubject(s)
COVID-19 , Psoriasis , Antibodies, Monoclonal, Humanized , Humans , Interleukin-6 , SARS-CoV-2ABSTRACT
PURPOSE: Hyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia. METHODS: The objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups. RESULTS: Blood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4-5)/8 (IQR: 6-9), P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%, P < 0.05; 11.2%/4.1%, P > 0.05; N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%, P < 0.01; 11.9%/7.6%, P > 0.05; N = 116/122, respectively]. CONCLUSION: The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Azetidines/administration & dosage , COVID-19 Drug Treatment , Purines/administration & dosage , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Administration, Oral , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azetidines/therapeutic use , Bangladesh , COVID-19/mortality , Comorbidity , Critical Care , Female , Hospital Mortality , Humans , Male , Middle Aged , Patient Readmission , Prospective Studies , Purines/therapeutic use , Pyrazoles/therapeutic use , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Sulfonamides/therapeutic use , Treatment OutcomeABSTRACT
Pneumonia associated with coronavirus disease 2019 (COVID-19) has been accounted for high mortality rate in severe COVID-19 worldwide, and additional serious scarcity of standard and effective anti-inflammatory drug in COVID-19 pneumonia management is a big challenge. Baricitinib, a Janus kinase (JAK) inhibitor, is a promising drug in COVID-19 pneumonia. This study aims to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥95% (in room air) and return in normal breathing function were lower in case group than the control group. The requirement of intensive care unit and mechanical ventilation support was higher in the control group than in the case group [29.4% (N = 17)/10% (N = 20), P < 0.05; 11.8% (N = 17)/5% (N = 20), P > 0.05), respectively]. Thus, an additional loading dose of baricitinib revealed better clinical outcome of patients with COVID-19 pneumonia.