Résumé :
|
Pompe disease is caused by a deficiency of acid alpha-glucosidase (GAA). Severe GAA deficiency manifests during infancy with rapidly progressing muscle weakness and cardiomyopathy. Most patients die by age 1 year. Two open-label studies (S1 and S2) were conducted in patients <6 months (S1, n=18) or >6-36 months (S2, n=21) of age. S1 patients were randomized to alglucosidase alfa at 20 or 40 mg/kg qow; all S2 patients started at 20 mg/kg qow. Mean age at treatment ± SD was 5.1 ±2.0 months (S1) and 15.7 ±11.0 months (S2), respectively. Median treatment duration for both studies was 120.5 weeks (range: <1–168). Cox regression analyses comparing study patients to similar historical controls; (S1 n=61; S2 n=84) indicated that in patients treated at <6 months, treatment reduced the risk of death by 95% and the risk of death or invasive ventilation by 91% (both with p <0.0001). In patients >6-36 months, treatment reduced the risk of death by 79% (p=0.0009) and the risk of death or invasive ventilation by 58% (p=0.02). Decrease in LV mass occurred in 94% (S1) and 81% (S2) of patients, respectively. In both studies, normal growth was seen in >80% of patients and clinically significant motor gains in 61%. Infusion-associated reactions occurred in 56%; IgG antibodies developed in 92%. Low IgG titres or a trend towards decreasing titres occurred in 74% of those who seroconverted. Patients with two null GAA mutations and high, sustained IgG titres were observed more frequently among those who died, needed ventilation, and/or had minimal motor response. These findings illustrate the clinical benefit of alglucosidase alfa in infants and children with Pompe disease. A more robust response was noted in patients treated at earlier stages of disease progression, underscoring the need for early diagnosis.
|