Phenotypes of Elosulfase Alfa–Induced Immediate Hypersensitivity Reactions and Long-term Outcomes of Desensitization in Mucopolysaccharidosis IVA

Background: Mucopolysaccharidosis type IVA (MPS IVA) is an ultra-rare lysosomal storage disease treated with enzyme replacement therapy (ERT) using Elosulfase alfa (ELA). However, ELA may induce immediate hypersensitivity reactions (I-HSRs), including anaphylaxis, and data on ELA-induced I-HSRs and rapid drug desensitization (RDD) are limited. Objective: This study aimed to evaluate the frequency, phenotypes, risk factors, and desensitization outcomes of ELA-induced I-HSRs in children with MPS IVA. Methods: Medical records of patients with MPS IVA between April 2004 and July 2023 were analyzed. I-HSRs were classified as Type I, cytokine-release syndrome (CRS), or mixed-type. Diagnostic testing and RDD protocols were evaluated. Logistic regression and receiver operating characteristic (ROC) analyses identified predictors of I-HSR occurrence. Results: Thirty-one patients were included (48% male); the median age at diagnosis was 45 months (6–203) and follow-up 109 months (1–234). ERT was given to 25 patients (81%) for a median of 66 months (1–98). I-HSRs occurred in 28%: 71% Type I (all anaphylaxis), 14% mixed, and 14% CRS; all were moderate to severe. Patients with I-HSRs had a significantly lower age at diagnosis (p = 0.021); diagnosis ≤30 months predicted I-HSR (AUC = 0.80; sensitivity 71.4%, specificity 83.3%, OR 12.5; p = 0.016). Four patients underwent 490 RDDs with only one mild breakthrough reaction (0.2%). Conclusion: ELA-induced I-HSRs are relatively frequent in MPS IVA, occur predominantly as Type I phenotypes, and are clinically significant. Younger age at diagnosis (≤30 months) markedly increases the risk of I-HSRs, and RDD is safe and effective long-term.