Efficacy and safety of oral chelators in treatment of patients with Wilson disease

Clin Gastroenterol Hepatol. 2013 Aug;11(8):1028-35.e1-2. doi: 10.1016/j.cgh.2013.03.012. Epub 2013 Mar 28.


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.

Keywords: ATP7B; D-penicillamine; DPA; Metabolic Disorder; WD; Wilson disease; Wilson's Disease; Wilsons disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Austria
  • Chelating Agents / administration & dosage*
  • Chelating Agents / adverse effects*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Germany
  • Hepatolenticular Degeneration / drug therapy*
  • Hepatolenticular Degeneration / pathology
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Penicillamine / administration & dosage*
  • Penicillamine / adverse effects*
  • Retrospective Studies
  • Treatment Outcome
  • Trientine / administration & dosage*
  • Trientine / adverse effects*
  • Young Adult


  • Chelating Agents
  • Penicillamine
  • Trientine