Enzyme replacement therapy desensitization in a child with infantile onset Pompe disease

Abstract

Background: Enzyme replacement therapy significantly reduces morbidity and mortality in patients with Pompe disease. Development of hypersensitivity reactions to enzyme replacement therapy is common and can adversely affect disease outcomes when treatment is halted or delayed.Objective: Our institution reports a case of successful alglucosidase alfa enzyme replacement therapy desensitisation in a 9-year-old girl with infantile onset Pompe disease.Methods: A desensitisation protocol was tailored to our patient with the help of a multidisciplinary team including the allergist, geneticist, nurses and pharmacists.Results: For our patient, desensitisation was successful using a multi-step three-fold dose escalation protocol. Conclusion:Desensitisation is possible in individuals with hypersensitivity reactions to enzyme replacement. Desensitisation protocols need to be tailored according to the patient's needs and responses to find a protocol that is safe, effective and simple.

Reacciones de hipersensibilidad a alglucosidasa alfa en enfermedad de Pompe: dos casos de desensibilización exitosa

“…Con respecto al tratamiento para las reacciones infusionales, se describen tres opciones. En primer lugar, la prevención y manejo estándar, donde se incluye la premedicación y la disminución de la velocidad de infusión; en segundo lugar, la inmunomodulación, cuyo objetivo es disminuir la respuesta de anticuerpos mediante la supresión de los linfocitos B, utilizando rituximab y metotrexate antes de administrar la primera dosis de alglucosidasa alfa en pacientes negativos para CRIM; y, finalmente, la desensibilización [17], con algunos casos reportados en la literatura para la desensibilización específica para la alglucosidasa alfa [3,[17][18][19][20][21][22].…”

Desensitization to drugs in children

“…Desensitization has been successfully described in laronidase (type-I mucopolyssacharidosis [MPS-I]), arylsulfatase B (MPS-VI), galsufase (MPS-VI), aglucosidase alfa (Pompe disease), and sebelipase alfa (lysosomal acid lipase deficiency) (Table 1). [36][37][38][39][40][41]…”

Immune responses to alglucosidase in infantile Pompe disease: recommendations from an Italian pediatric expert panel

“…As infusion-associated reactions of various mechanisms have similar presentation, clinicians are unable to use clinical history to predict these events and guide management [74]. After a potential hypersensitivity reaction has been identified, three approaches are possible: standard prevention and management, immunomodulation, and desensitization [75].…”

“…To our knowledge, 10 cases (8 pediatric, 2 adults) affected by Pompe disease and subjected to desensitization protocol have been reported [14,56,74,75,79,81,82] (Table 6). Of note, recently Emecen Sanli et al reported the first case of successful concomitant immunotolerance induction and desensitization protocol in a CRIM negative 7-month-old male patient, that have developed IARs and anti-rhGAA antibodies (1:12,800) [83].…”

“…If anaphylaxis is severe: 1/1,000,000-1/10,000 of the full therapeutic dose. If positive skin test, the starting dose can be determined based on the endpoint titration Concentration increase[74] Doubling or three-fold every 15-20 min until the therapeutic dose is achieved…”