P.72Optimizing long-term outcome in classic infantile Pompe patients: effects of higher dosing and immunomodulation

Abstract

Pompe disease is a metabolic myopathy, caused by deficiency of acid alpha-glucosidase. Complete deficiency of this enzyme leads to the severe classic infantile phenotype. Without treatment these patients usually die before one year of age. The introduction of enzyme replacement therapy (ERT; alglucosidase alfa), has substantially improved lifespan and motor development. However, treatment response varies between patients. Previous studies have suggested that outcome is dose dependent, and negatively affected by antibody formation. International consensus on dose has not been established, and dose regimen vary from 20mg/kg/every other week (eow) up to 40mg/kg/week. To study the effect of different dose regimen, we compared the long-term outcome of classic infantile Pompe patients treated with 20 mg/kg eow to those treated with 40 mg/kg/week, and studied the additional effect of immunomodulation. We prospectively studied 18 patients, six in the 20mg group and 12 in the 40mg group. Five patients were CRIM-negative, two in the 20mg, three in the 40mg group. Outcome parameters were (ventilator-free) survival, motor development and antibody formation. Survival was 92% in de 40mg group, compared to 67% in the 20mg group, with ventilator-free survival being 92% and 50%. At study end all three CRIM negative patients in the 40mg group were alive, whereas both CRIM negative patients in the 20mg group died. In the 40mg group 92% learned to walk, compared to 67% in the 20mg group. At 3 years of age none of the patients in the 40mg group had lost the ability to walk, while in the 20 mg group only 33% was still ambulant. Peak antibody titers ranged from 1:1250-1:31,250 (20mg/kg/eow) to 1:250-1:800,000 (40mg/kg/w). Five patients of the 40mg group received immunomodulation in an ERT-naïve setting, which did not prevent antibody formation. This study shows that classic infantile patients treated with 40 mg/kg/week have a better (ventilator-free) survival and motor outcome.