JAK ANTAGONISTS AND IL-6 INHIBITORS FOR MANAGEMENT OF SARS-COV-2 INFECTION: A SYSTEMIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

ABSTRACT

SESSION TITLE Medications and Pulmonary Rehabilitation in COVID-19 Posters SESSION TYPE Original Investigation Posters PRESENTED ON 10/18/2022 0130 pm - 0230 pm PURPOSE: JAK-antagonists and IL-6 inhibitors are immunomodulators indicated for inflammatory pathologies. With the COVID pandemic, these drugs have been utilized in management of hospitalized patients with SARS-CoV-2. Selection between the two drug classes has been attributed to availability and physician comfort. No existing comparative randomized trial to date. METHODS: We performed a systematic review and network meta-analysis using PRISMA guidelines. Randomized controlled trials evaluating various IL-6 inhibitors and JAK-antagonists were included. Outcomes were 28-day mortality and progression, defined as advancement to mechanical ventilation or ECMO. Subgroup analysis of concomitant steroid and remdesivir usage was also analyzed. P-scores were used to rank treatment groups in class and drug specific classifications. RESULTS: We identified 33 RCTs with 13,680 patients that met our selection criteria. Our analysis revealed that IL-6 inhibitor versus JAK antagonists, IL-6 was associated with greater odds of mortality (OR = 1.23 (1.13, 1.34), p = 0.01). This finding was also evident in the subgroup receiving concomitant steroids and remdesivir (OR = 1.41 (1.00, 2.00), p = 0.049) but no significant differences observed for the outcome of progression in this group. Baricitinib is associated with a significant 30% reduction in 28-day mortality compared to Tocilizamab CONCLUSIONS: JAK-a vs control and IL-6 inhibitors vs control exhibit mortality reducation but JAKs did so at a greater rate. Similarly, for drug specific comparisons, Baricitinib reduced mortality by the greatest amount. Only IL-6 inhibitors seemed to have a significant effect on preventing progression. Siltuximab and Tocilizumab were both effective against control but Tocilizumab reduced progression the best. As a secondary goal, a sub-group analysis on concomitant steroid and Remdesivir usage demonstrated that for drug specific comparisons, Baricitinib performed better for reducing mortality & Tocilizumab continued to be the most effective in preventing progression. However, with Remdesivir and steroids, there was no significant difference between Baricitinib and Tocilizumab in decreasing mortality. This is contrary to the findings without steroids. CLINICAL IMPLICATIONS We hope to use this data to help clinical decision making between JAK-a and IL-6 inhibitors which are currently being used interchangeably for the management of COVID-19 in hospitalized patients. Through our study results and analysis, we recommend that Baricitinib be used to decrease mortality rates and disease progression for the treatment of COVID-19 with concomitant therapy corticosteroids and Remdesivir. Moving forward with this data, we aim to help restructure COVID-19 treatment algorithms regarding IL-6 and JAK antagonists. DISCLOSURES No relevant relationships by Monica Bhagavan No relevant relationships by rukhsaar khanam No relevant relationships by Anant Naik No relevant relationships by Aashka Shah