Individualised low-dose alglucerase therapy for type 1 Gaucher's disease

Abstract

Previous studies have shown that enzyme supplementation therapy with alglucerase for type 1 Gaucher's disease is effective at doses of 30-130 U/kg per month. Since both the clinical presentation and the response to therapy in Gaucher's disease are highly variable, individual dosing seems indicated. This notion, as well as the high costs of alglucerase and the unknown long-term side-effects, led us to investigate the efficacy of an individualised very low dose of alglucerase. Twenty-five adults with symptomatic type 1 Gaucher's disease (thirteen splenectomised) received alglucerase 1.15 U/kg three times a week (15 U/kg per month). Every 6 months, the dose was halved, maintained, or doubled, according to the response (based on haematological variables and liver and spleen volume). After 6 months of treatment, eighteen (72%) patients had a response (seventeen moderate, one good). After 12 months (in nineteen patients) and 18 months (in seven patients), all had sustained improvement. Severe splenomegaly resulted in slower haematological responses. Our results are similar to those obtained by others with higher-dose regimens and better than a low-dose regimen of 10U/kg every 2 weeks. We conclude that very low initial doses of alglucerase, when administered frequently, are effective and cost-saving in the treatment of type 1 Gaucher's disease.