Economic malpractice in the treatment of Gaucher's disease

Abstract

0 nly rarely can a physician save the health care system hundreds of thousands of dollars a year in the treatment of a single patient. The strategy that is documented in the paper by Zimran et all in this issue provides that opportunity in the management of patients with Gaucher’s disease. When Barton et al2 first investigated alglucerase in a small group of patients with this disease, they utilized a very high dose, reasoning that it was important to clearly define whether it was an effective treatment for the clinical manifestations of the disease. Even before their paper appeared, the FDA took the unusual step of approving the drug on the basis of a clinical trial carried out on only 12 patients, with 10 of those patients receiving the drug at only one dose level, 60 U/kg every two weeks, and 2 patients receiving 60 U/kg weekly. Even though no clinical dosage-response data had been developed, approval of the drug was a rational step. The F’DA displayed commendable courage in acting promptly; more detailed dosage data could be developed later. Over the past 3 years, it has become increasingly clear that the original dose was, indeed, much higher than needed, and that the dosage schedule used was far from optimal. The sparsely distributed specific mannose receptors on macrophages are outnumbered by three or four orders of magnitude by low affiity nonspecific receptors on endothelial cells and all other cells tested.3 As a consequence, very little of the infused enzyme reaches the macrophage. On theoretical grounds, one can predict that a much larger proportion of a small dose would reach the target than that of a large dose. Our clinical results4a5 and those reported by Zimran et al’ in this issue have proved that there is no longer any justification for the administration of 130 U/kg or even 65 U/kg every month as was originally recommended except, as Zimran et al state, “when cost is not an issue.” But at more than $400,000 per year for a 70-kg patient, cost is always an issue. In reality, even the low doses used by Zimran et al may be high on the dosage-response curve. Hollak et al6 have shown that most patients enjoy a satisfactory response to one-half of the dose that was used by the Israeli group and by ours. They propose an eminently