Heart & lung : the journal of critical care · 2026
Body mass index and baricitinib treatment effect in hospitalized adults with COVID-19: A secondary analysis of ACTT-2.
СтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Rigsby Rachel, Gaulton Timothy G
Аннотация
BACKGROUND: Obesity alters inflammatory signaling in critical illness. Whether body weight modifies response to targeted immunomodulatory therapy remains unknown.
OBJECTIVES: To assess whether body mass index (BMI) and metabolic phenotypes modify the treatment effect of baricitinib in hospitalized adults with COVID-19.
METHODS: We conducted a secondary analysis of the Adaptive COVID-19 Treatment Trial 2, which randomized participants to baricitinib plus remdesivir versus placebo plus remdesivir between May and July 2020. We included participants with BMI 18.5 to <50 kg/m². For the primary outcome of time to recovery, we used Fine-Gray competing risk regression with linear BMI and a BMI × treatment interaction, adjusted for age, sex, and baseline severity, with heterogeneity tested by likelihood ratio test. We also tested heterogeneity across four metabolic phenotype groups based on BMI (<30 vs ≥30 kg/m²) and the presence of diabetes or hypertension.
RESULTS: Among 942 participants, mean age was 56 years and 58% required advanced respiratory support at baseline. Subdistribution hazard ratios ranged from 1.11 (95% CI, 0.85-1.46) at BMI 20 kg/m² to 1.26 (95% CI, 0.93-1.70) at BMI 45 kg/m² (BMI × treatment interaction: χ²=0.22, P=.64). Among 925 participants with complete comorbidity data, treatment effects across four metabolic subgroups varied from 1.11 to 1.26 (χ²=0.58, P=.90).
CONCLUSION: In this early pandemic population, we did not observe substantial variation in baricitinib treatment effect across BMI or metabolic subgroups, though clinically meaningful heterogeneity cannot be excluded. These findings inform broader questions of how obesity interacts with immunomodulatory therapy in critical illness.
OBJECTIVES: To assess whether body mass index (BMI) and metabolic phenotypes modify the treatment effect of baricitinib in hospitalized adults with COVID-19.
METHODS: We conducted a secondary analysis of the Adaptive COVID-19 Treatment Trial 2, which randomized participants to baricitinib plus remdesivir versus placebo plus remdesivir between May and July 2020. We included participants with BMI 18.5 to <50 kg/m². For the primary outcome of time to recovery, we used Fine-Gray competing risk regression with linear BMI and a BMI × treatment interaction, adjusted for age, sex, and baseline severity, with heterogeneity tested by likelihood ratio test. We also tested heterogeneity across four metabolic phenotype groups based on BMI (<30 vs ≥30 kg/m²) and the presence of diabetes or hypertension.
RESULTS: Among 942 participants, mean age was 56 years and 58% required advanced respiratory support at baseline. Subdistribution hazard ratios ranged from 1.11 (95% CI, 0.85-1.46) at BMI 20 kg/m² to 1.26 (95% CI, 0.93-1.70) at BMI 45 kg/m² (BMI × treatment interaction: χ²=0.22, P=.64). Among 925 participants with complete comorbidity data, treatment effects across four metabolic subgroups varied from 1.11 to 1.26 (χ²=0.58, P=.90).
CONCLUSION: In this early pandemic population, we did not observe substantial variation in baricitinib treatment effect across BMI or metabolic subgroups, though clinically meaningful heterogeneity cannot be excluded. These findings inform broader questions of how obesity interacts with immunomodulatory therapy in critical illness.