Tofacitinib Rescue for Refractory Drug-Induced Liver Injury With Severe DRESS: A Prospective Proof-of-Concept Study

Drug-induced liver injury (DILI) with severe DRESS carries high mortality, yet rescue therapies for corticosteroid-refractory cases remain undefined. We hypothesized that JAK inhibition could reverse refractory liver injury by targeting the underlying cytokine storm. In this prospective proof-of-concept study, consecutive patients with severe DRESS-associated DILI refractory to corticosteroids (persistent/worsening liver injury) received oral tofacitinib rescue. Key assessments were the normalisation of liver biochemistries. Despite initial corticosteroids, all four patients exhibited progressive severe injury (median peak ALT 1126 U/L). Tofacitinib rapidly reversed liver injury in all cases. Transaminases normalised or near-normalised (median: 48 days), total bilirubin normalised, and cutaneous symptoms resolved completely. Notably, baseline positive autoantibodies seroconverted to negative. No severe adverse events occurred (median follow-up: 274 days). Tofacitinib shows promise as a rescue strategy for corticosteroid-refractory DILI with severe DRESS. The rapid recovery underscores the JAK-STAT pathway's pathogenic role in this setting.