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INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.
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BACKGROUND/GOALS: There are limited data regarding the frequency and proportionality of drug-induced hepatotoxicity in the United States. We sought to determine the scope of nonfulminant drug-induced hepatitis as seen in a community-based hepatology referral service. STUDY: From a population of 4,039 outpatients referred for evaluation of acute (n = 96) and chronic (n = 3,943) liver disease over a 10-year period, we reviewed the records of those patients diagnosed with acute bona fide drug-induced hepatitis. RESULTS: Thirty-two patients presented with self-limited acute drug-induced hepatitis, representing 0.8% of all hepatology patients and 33% of those patients presenting with acute liver injury. Antibiotics (amoxicillin/clavulanic acid, minocycline, nitrofurantoin, an investigational ketolide antibiotic, trimethoprim-sulfamethoxazole, and trovafloxacin) were the class of drugs most frequently implicated (14 of 32; 44%), while amiodarone was the single agent most commonly associated with liver injury (7 of 32; 22%). The mean age of affected patients was 52.2 years, and we found a male predominance (18 of 32; 56%). The mean time to biochemical resolution after discontinuation of the offending agent was 14.1 weeks. CONCLUSIONS: Drug-induced hepatitis is an uncommon entity in clinical hepatology but does represent a significant proportion of acute self-limited liver disease in the United States. Antibiotics and amiodarone were the most common drug culprits in our population. Time to resolution following the discontinuation of the offending agent may be protracted. Prospective studies are needed to further assess the burden of drug-induced liver injury.
