[Idursulfase desensitization in a child with Hunter syndrome (mucopolysaccharidosis II)]. / Desensibilización con idursulfase en un niño con síndrome de Hunter (mucopolisacaridosis II).

Enzyme replacement therapy with idursulfase decreases morbidity and improves quality of life of patients with mucopolysaccharidosis ii. Immediate hypersensitivity reactions to this drug have been described. Desensitization is a treatment that induces temporary tolerance to a culprit drug, allowing the allergic patient to receive the medication. We present the case of a 7-year-old patient diagnosed with Hunter syndrome who presented, after 4 years of treatment, two episodes of anaphylaxis during the infusion of idursulfase. Detection of specific immunoglobulin E was carried out using skin tests, with intradermal reaction at a 1/10 dilution (0.2 mg/ml) being positive. A 12-step desensitization protocol was performed without presenting adverse events. The allergological evaluation and the possibility of desensitization were useful tools in the management of our patient.

La terapia de reemplazo enzimático disminuye la morbilidad y mejora la calidad de vida de los pacientes con mucopolisacaridosis ii. Se han descrito reacciones de hipersensibilidad inmediata a este fármaco. La desensibilización es un tratamiento que induce la tolerancia temporaria a una droga y permite al paciente alérgico recibir la medicación. Se presenta el caso de un niño de 7 años con diagnóstico de síndrome de Hunter que, luego de 4 años de tratamiento con idursulfase, tuvo dos episodios de anafilaxia durante la infusión del fármaco. Se detectó inmunoglubulina E específica mediante pruebas cutáneas, y fue positiva la intradermorreacción con dilución 1/10 (0,2 mg/ml). Se realizó un protocolo de desensibilización de 12 pasos, sin presentar eventos adversos. La evaluación alergológica y la posibilidad de desensibilización constituyeron herramientas útiles en el manejo de nuestro paciente.

A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4-7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy.

PURPOSE: The primary objective of this study was to determine the safety of idursulfase in Hunter syndrome patients aged 5 years or younger. METHODS: Idursulfase (0.5 mg/kg) was administered intravenously on a weekly basis (52 infusions per patient) in an open-label study. Safety monitoring included adverse events, anti-idursulfase antibodies, vital signs, physical examination, 12-lead electrocardiogram, concomitant medications or procedures, and laboratory testing (clinical chemistry, hematology, and urinalysis). The following exploratory efficacy outcomes were assessed at baseline and at weeks 18 or 36 or 53: urinary glycosaminoglycan levels, liver or spleen size, developmental milestones, and growth indices. Pharmacokinetic parameters were assessed at week 27. RESULTS: Twenty-eight boys aged 1.4-7.5 years were enrolled (one discontinued for noncompliance) in the study. All the patients reported adverse events (16 patients (57%) reported possibly or probably treatment-related adverse events). The only severe adverse event was sleep apnea (two patients); others were mild or moderate. Sixteen patients had infusion-related adverse events, a similar proportion as previously reported. Thirteen patients (46%) experienced at least one serious adverse event: pyrexia and bronchopneumonia were the most common (three patients each). No clinically important drug-related changes in laboratory parameters or vital signs or electrocardiograms were reported. Nineteen patients (68%) developed anti-idursulfase immunoglobulin G antibodies. Growth rates remained within normal age-related ranges. Developmental quotients were lower than normal but remained stable. By week 18, organ size and urinary glycosaminoglycan levels decreased as compared with baseline and remained stable throughout the study. CONCLUSION: Idursulfase safety, tolerability, and efficacy were similar to that previously reported in males ≥5 years.

Eficácia e segurança da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem comparação com placebo: revisão sistemática e metanálise / Efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II with and without comparison to placebo: systematic review and meta-analysis / Eficacia y seguridad del tratamiento con idursulfasa en pacientes con mucopolisacaridosis tipo II con y sin comparación con el placebo: revisión sistemática y metaanálisis

A mucopolissacaridose tipo II (MPS II) é uma doença genética de amplo espectro clínico, caracterizada por deficiência da enzima iduronato-2sulfatase. Revisão sistemática avaliou a eficácia e segurança da terapia de reposição enzimática (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados até 30 de novembro de 2012. Apenas cinco estudos preencheram os critérios de inclusão (ensaios clínicos randomizados - ECRs, ECRs abertos ou séries de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanálise foi realizada para capacidade vital forçada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudanças significativas em ambas as variáveis; também foi encontrado risco aumentado de reações leves relacionadas à infusão e de desenvolvimento de anticorpos IgG à IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS é segura e tem benefício potencial em MPS II, mas estudos adicionais são necessários.

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.

La mucopolisacaridosis tipo II (MPS II) es una enfermedad genética de amplio espectro clínico, caracterizada por una deficiencia de la enzima iduronato-2-sulfatasa. El objetivo fue evaluar la seguridad y eficacia de la Terapia de Reemplazo Enzimático (TRE) con idursulfasa (IDS) en la MPS II. En las bases PubMed/MEDLINE, EMBASE, LILACS y Cochrane Library se inició la búsqueda hasta el 30 de noviembre de 2012. Sólo cinco estudios cumplieron los criterios de inclusión (ensayos controlados aleatorios -ECA, o ECA abiertos o series de casos prospectivo incluyendo > 5 pacientes y evaluación de los resultados pertinentes). El metaanálisis se realizó para la capacidad vital forzada (FVC; absoluta y %) y la distancia caminada en 6 minutos, con cambios significativos en ambas variables; el riesgo también se encuentra aumentado por reacciones leves y anticuerpos IgG, relacionados con la infusión con IDS. El TRE con IDS es seguro y tiene un beneficio potencial en la MPS II, pero se necesitan estudios adicionales.

[Efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II with and without comparison to placebo: systematic review and meta-analysis]. / Eficácia e segurança da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem comparação com placebo: revisão sistemática e metanálise.

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.