Treatment of Neuronal Ceroid Lipofuscinosis Type 2 with Cerliponase Alfa: A Systematic Review and Single-Arm Meta-Analysis of Two Studies

Background: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disorder caused by CLN2 gene mutations, leading to ceroid lipofuscin accumulation and progressive neurodegeneration. Cerliponase alfa, a recombinant tripeptidyl peptidase-1, may improve aspects of disease progression, but common hypersensitivity and infusion reactions, along with a limited number of studies and lack of controlled trials, constrain the generalizability of these findings. Purpose: This systematic review and single-arm meta-analysis aims to evaluate the efficacy and safety of cerliponase alfa in treating children with CLN2. Methods: Following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the protocol was registered in PROSPERO (CRD42024541000). We included prospective and retrospective cohorts of CLN2 patients treated with cerliponase alfa. A comprehensive search was conducted in PubMed, Embase, and Cochrane Central up to February 2024. Clinical outcomes and adverse effects were analyzed using a random effects model to compute pooled proportions with 95% CIs. Study quality was assessed with the Cochrane Risk of Bias tool for Non-randomized Studies. Results: From 318 records, 3 observational studies with 55 patients were included. A Clinical Rating Scale score of 0 or 1 was seen in 24% of patients. Generalized tonic-clonic seizures occurred in 41%, and dystonia in 15%. Adverse events included pyrexia (60%), hypersensitivity (82.6%), anaphylaxis (3%), and infusion-associated reactions (18.31%). Significant heterogeneity was observed. Conclusion: Cerliponase alfa may improve clinical outcomes in children with CLN2, though adverse effects might be prevalent.