REMDESIVIR PLUS DEXAMETHASONE VS TOCILIZUMAB OR BARICITINIB SUPPLEMENTATION INITIATED INSIDE 48 HOURS OF INDEX COVID-19 HOSPITALIZATION IN ICU PATIENTS

ABSTRACT

SESSION TITLE Critical Care Management of COVID-19 SESSION TYPE Original Investigations PRESENTED ON 10/17/2022 0130 pm - 0230 pm PURPOSE: We hypothesized that supplementation of NIH recommended remdesivir (REM) and dexamethasone (DEX) combination treatment with tocilizumab (TOCI) or baricitinib (BARI) initiated inside 48h of index hospitalization would enhance reduction of inflammatory markers and discharges to home in adults over 18 years old who received intensive care. METHODS: Electronic medical record data were extracted under IRB exemption. Treatment responsiveness was estimated using delta in C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) and D-dimer levels from assays respectfully respectively first within 24h and last between 25-72h of initiating REM/DEX with vs without TOCI or BARI. Confounder balanced multigroup contrasts were significant when p<.017. RESULTS: Between March 10, 2020 and January 31, 2022, 891 COVID-19 patients were admitted to the ICU with 459 receiving REM/DEX (n=326) or supplemented with BARI (n=85) or TOCI (n=41). Results are sequenced as REM/DEX, REM/DEX/BARI, REM/DEX/TOCI. Age was 67[57,77] (p<.0001) vs. 61[51,69] and 62[48,68] among statistically similar sex (male, 65%;female, 35%) and race (White, 76%;Black, 8%;Other, 16%) distributions and BMI (32[27,38] kg/m2). Hypertension (70%), obesity (59%), diabetes (38%), deficiency anemia (36%), coagulopathy (29%) chronic pulmonary disease (22%), and renal failure (17%) were similarly distributed. Initial CRP, ferritin, LDH and D-dimer levels -24h to +24h of REM/DEX first dose respectively were 12.1[7.1,18.2], 11.4[7.5,15.7], 14.0[11.2,21.0] mg/dL;811[441,1390], 1178[529,1956], 1110[653,1810] ng/mL (REM/DEX, p=.013);437[321,576], 516[403,695], 518[397,692] U/L (REM/DEX, p=.0001);and 1.02[0.67,2.28], 0.97[0.72,1.88], 1.47[0.86,2.19] ug/mL. Responsiveness quantified using last levels 25h-72h post REM/DEX first dose respectively included -3.4[-7.2,-0.6], -4.3[-7.7,-1.9], -7.2[-10.1,-3.6] mg/dL (REM/DEX/TOCI, p=.014);7[-125,202], -94[-329,69], -29[-181, 535] U/L;-3[-74,80], 85[-58,273], -33[-188,-3] U/L (p=.051);and 0.00[-0.50,1.05], 0.88[-0.45,10.52], -0.01[-0.38,0.50] ug/mL. ICU length of stay (LOS) was 6[3,13], 6[3,12], 8[5,15] days (p<.00001) with hospital LOS of 16[10,24], 20[12,33], 17[11,23] days (REM/DEX/BARI, p<.021). Hospital mortality was 51%, 71%, 43%, with REM/DEX/BARI exhibiting increase (p=.0019), but REM/DEX/TOCI numerically lowest (p>.017). Discharge to home was 24%, 18%, 43%, with REM/DEX/TOCI demonstrating increase (p=.0038). CONCLUSIONS: REM/DEX/TOCI combination therapy provided largest reduction of inflammatory markers and mortality while substantially increasing percentage of discharges to home. REM/DEX treatment responsiveness was adversely impacted by addition of baricitinib, while augmented by tocilizumab. CLINICAL IMPLICATIONS Our findings highlight need to refine early longitudinal biomarker-tracking to identify patient-centric COVID-19 treatment responsiveness to COVID-19 directed treatments. DISCLOSURES No relevant relationships by Qassem Abdelal No relevant relationships by Kevin Dawkins No relevant relationships by Karen Hamad No relevant relationships by Natalia Lattanzio No relevant relationships by Richard Walo Jr No relevant relationships by Wilhelmine Wiese-Rometsch No relevant relationships by Stephanie Williams