Respiratory effects of off label anakinra in critically ill neonates: a 15-patient observational cohort study

Background: Interleukin-1 (IL-1)-mediated inflammation can contribute to lung injury, impaired alveolar development, and pulmonary vascular dysfunction in critically ill neonates. Anakinra, a recombinant IL-1 receptor antagonist, has emerged as a potential adjunct therapy in severe neonatal hyperinflammatory and respiratory conditions, but evidence in this population remains limited. Methods: We conducted a retrospective observational study of 15 neonates treated off label with anakinra (10 mg/kg/day in two doses) at a tertiary neonatal intensive care unit between 2021 and 2025. Clinical indications included severe or evolving bronchopulmonary dysplasia (BPD), secondary hemophagocytic lymphohistiocytosis (HLH), pulmonary hypertension, interstitial lung disease and complex congenital anomalies. Respiratory support was evaluated at treatment initiation and at predefined follow-up timepoints up to 60 days. Results: At baseline, 73% of infants required mechanical ventilation and 27% non-invasive ventilation. By the end of treatment (data available for 14/15 infants), mechanical ventilation decreased to 21% (absolute reduction 52%, relative reduction 71%), while spontaneous breathing with or without supplemental oxygen increased to 64%. All infants survived. Anakinra was generally well tolerated: transient transaminase elevations occurred in 40%, γGT increases in 20%, and transient neutropenia in 13%, with no clinically significant hepatotoxicity, allergic reactions, or seizures. Conclusions: In this largest neonatal cohort to date, Anakinra administration was associated with improvements in respiratory status, although a direct causal relationship cannot be established, and a favorable safety profile. Multicenter randomized controlled trials are warranted to confirm these findings, especially in preterm infants at risk of developing bronchopulmonary dysplasia.