1. Efficacy and safety of oral chelators in treatment of patients with Wilson disease
- Author
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Uta Merle, Ulrike Reuner, Daniela Ferenci–Foerster, Peter Ferenci, Wolfgang Stremmel, Rudolf E. Stauber, Jean Marc Trocello, Heinz Zoller, Karl Heinz Weiss, Hartmut Schmidt, Andreas Maieron, Florentine F. Thurik, Harald Hefter, Mark Schäfer, Roderick H. J. Houwen, Daniel Gotthardt, Ulrike Teufel, and Franziska Wiegand
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,medicine.medical_treatment ,Disease ,Liver transplantation ,Trientine ,Cohort Studies ,Young Adult ,Hepatolenticular Degeneration ,Internal medicine ,Germany ,medicine ,Humans ,In patient ,Chelation therapy ,Adverse effect ,Child ,Chelating Agents ,Retrospective Studies ,Hepatology ,business.industry ,Metabolic disorder ,Penicillamine ,Gastroenterology ,Infant ,Middle Aged ,medicine.disease ,Surgery ,Discontinuation ,Wilson's disease ,Treatment Outcome ,Austria ,Child, Preschool ,Female ,business - Abstract
Background & Aims Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms. Chelating agents (D-penicillamine, trientine) are used as first-line therapies for symptomatic patients, but there are few data from large cohorts. We assessed the safety of D-penicillamine and trientine therapy and outcomes of patients with Wilson disease. Methods We performed a retrospective analysis of data on 380 patients with Wilson disease from tertiary care centers in Germany and Austria, and 25 additional patients from the EUROWILSON registry. Chelator-based treatment regimens were analyzed for their effect on neurologic and hepatic symptoms and for adverse events that led to discontinuation of therapy (Kaplan–Meier estimation; data were collected for a mean of 13.3 y after therapy began). Results Changes in medication were common, resulting in analysis of 471 chelator monotherapies (326 patients receiving D-penicillamine and 141 receiving trientine). Nine of 326 patients treated with D-penicillamine and 3 of 141 patients given trientine underwent liver transplantation. Adverse events leading to discontinuation of treatment were more frequent among those receiving D-penicillamine than trientine ( P = .039). Forty-eight months after therapy, hepatic deterioration was reported in only 4 of 333 patients treated initially with a chelating agent. Hepatic improvements were observed in more than 90%, and neurologic improvements were observed in more than 55%, of therapy-naive patients, and values did not differ significantly between treatments. However, neurologic deterioration was observed less frequently in patients given D-penicillamine first (6 of 295) than those given trientine first (4 of 38; P = .018). Conclusions Chelating agents are effective therapies for most patients with Wilson disease; D-penicillamine and trientine produce comparable outcomes, although D-penicillamine had a higher rate of adverse events. Few patients receiving chelation therapy had neurologic deterioration, which occurred more frequently in patients who received trientine.
- Published
- 2013