Hypersensitivity reactions and enzyme replacement therapy: Outcomes and safety of rapid desensitization in 1,008 infusions

• Published in: The journal of allergy and clinical immunology in practice (Cambridge, MA) Vol. 10; no. 3; pp. 870 - 873.e1
• Main Authors: Aranda, Carolina Sanchez, Aun, Marcelo Vivolo, Souza, Carolina Fischinger Moura de, Pinto, Louise Lapagesse de Camargo, Porras-Hurtado, Gloria Liliana, Salgado, Omar Francisco Sierra, Arantes, Rodrigo Rezende, Martins, Ana Maria, Solé, Dirceu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2022; Elsevier Limited
• Subjects: Allergies; Antineoplastic Agents - therapeutic use; Cardiac arrhythmia; Desensitization (Psychology); Desensitization, Immunologic; Drug dosages; Drug Hypersensitivity - drug therapy; Drug Hypersensitivity - therapy; Enzyme Replacement Therapy - adverse effects; Enzymes; Erythema; Humans; Hypersensitivity; Immunoglobulin E; Monoclonal antibodies; Mucopolysaccharidosis; Nausea; Patients; Pruritus; Quality of life; Respiratory function; Skin tests; Tachycardia; Urticaria; Vomiting
• ISSN: 2213-2198; 2213-2201
• DOI: 10.1016/j.jaip.2021.10.052

Clinical Implications Enzyme replacement therapy (ERT) discontinuation significantly worsens visceromegaly, respiratory function, and walking capacity in patients with mucopolysaccharidoses. Because ERT is the only possible therapeutic alternative for most patients, hypersensitivity reactions are a cause of early treatment discontinuation. The intradermal tests were performed with diluted (1/100 and 1/10) and pure concentrations according to our previous data showing this is nonirritating.5 Both tests were performed and interpreted according to the European guidelines.4 As per standard guidance,2 we decided to offer RDD for patients with a confirmed hypersensitivity reaction with no equally effective therapeutic alternative. Because all patients had positive skin tests and were in need of ERT, all patients were offered RDD. [...]the RDD consisted of administrating elosulfase alfa (MPS IVA) or galsulfase (MPS VI) in a 12-step or a 16-step protocol as proposed by Castells and coauthors.2,6 The choice between both protocols was performed based on risk stratification, according to the severity of the initial reaction, as previously described by Sloane and colleagues.3 All protocols were performed in settings in which resuscitation personnel and resources were readily available.2 All the enzyme infusions were only conducted if patients were considered healthy. All authors critically revised the text and approved the final manuscript.Online Repository Patient number ERT-induced IHR Brown classification of IHR SPT IDT Breakthrough reactions during the RDD Breakthrough reactions clinical features Breakthrough reactions∗ Management of future RDDs 1 Flushing (erythema and/or warmth), pruritus, urticarial, and nausea Grade 2 Positive Positive Yes Step 12 (twice) Flushing (erythema and/or warmth), pruritus Grade 1 Change from 12-step to 16-step protocol 2 Vomiting and SpO2 < 92% at any stage Grade 3 NA Positive No No NA Change from 16-step to 12-step protocol 3 Flushing (erythema and/or warmth), pruritus, urticarial, and tachycardia Grade 1 Positive Positive No No NA NA 4 Flushing (erythema and/or warmth), pruritus, urticaria, tachycardia, and vomiting Grade 2 Positive NA Yes Step 12 Urticaria Grade 1 Change from 12-step to 16-step protocol 5 Flushing (erythema and/or warmth), pruritus, urticarial, and vomiting Grade 2 Positive Positive Yes Various steps† Pruritus, urticarial, and nausea Grade 2 Change from 12-step to 16-step protocol and administration of omalizumab 6 Flushing (erythema and/or warmth), pruritus, and urticaria Grade 1 Positive Positive No No NA NA Table I Characterization of the IRR and the breakthrough reactions presented by the enrolled patients before and after the