RESUMEN
BACKGROUND: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. METHODS: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability. RESULTS: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p < .01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found. CONCLUSION: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.
Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Enfermedad de Fabry/tratamiento farmacológico , Isoenzimas/administración & dosificación , alfa-Galactosidasa/administración & dosificación , Adulto , Anciano , Esquema de Medicación , Enfermedad de Fabry/patología , Femenino , Humanos , Infusiones Intravenosas/métodos , Isoenzimas/uso terapéutico , Masculino , Persona de Mediana Edad , alfa-Galactosidasa/uso terapéuticoRESUMEN
Patients with Pompe disease have realized significant medical benefits due to enzyme replacement therapy (ERT) infusions with alglucosidase alfa. However, regular infusions are time-consuming. Utilizing recommended infusion rates, infusion duration is 3h 45min for a patient receiving the standard dose of 20mg/kg, not including additional time needed for preparation of ERT, assessment of vital signs, intravenous access, and post-infusion monitoring. Recent studies have demonstrated increased effectiveness of higher dose of ERT (40mg/kg) in infantile-onset Pompe disease (IOPD), which increases the infusion duration to 6h 36min. Increased infusion durations compound the psychosocial burden on patients and families and potentially further disrupt family activities and obligations. We developed a stepwise infusion rate escalation protocol to administer higher dose ERT safely while decreasing infusion duration, which has been implemented in 15 patients to date. Reported here in detail are five patients with IOPD on 40mg/kg/weekly ERT in whom infusion duration was decreased with individualized, stepwise rate escalation. All patients tolerated rate escalations above the recommended rates without experiencing any infusion associated reactions and experienced a reduction in infusion duration by 1h and 24min with a corresponding increase in reported satisfaction. Our experience with ERT rate escalation is presented. SYNOPSIS: A careful stepwise method of enzyme replacement therapy (ERT) rate escalation can safely reduce infusion duration in patients with Pompe disease.