A Single-Center Review of Infusion-Associated Reactions in Patients with CLN2 Disease Receiving Cerliponase Alfa

Background: Cerliponase alfa is an intracerebroventricular (ICV) enzyme replacement therapy (ERT) and the only approved treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) disease. While generally well tolerated, infusion-associated reactions (IARs), including hypersensitivity events and anaphylaxis, remain a recognized safety consideration. Methods: This single-center, retrospective study describes the incidence and management of IARs in pediatric patients with CLN2 receiving long-term ICV cerliponase alfa at Great Ormond Street Hospital, London, United Kingdom. Results: Over a 10-year period (2014–2024), 31 patients received approximately 2705 ICV infusions. Eleven patients experienced at least one IAR. Most reactions were mild and transient, typically consisting of pyrexia, vomiting, or rash, and were managed conservatively with antipyretics and antihistamines. Four patients required steroid intervention following recurrent or more pronounced symptoms, which led to improved infusion tolerance. One patient experienced a single episode of anaphylaxis that required treatment with intramuscular adrenaline and intravenous hydrocortisone. Therapy was continued with a revised pre-medication regime, with no further severe reactions. Conclusions: These findings demonstrate that IARs to ICV cerliponase alfa are typically mild and readily manageable within a multidisciplinary framework. They highlight the importance of structured infusion protocols, vigilant monitoring strategies, and a coordinated management approach to ensure the long-term safety of ERT for children with CLN2 disease.