title: Efficacy and safety of oral chelators in treatment of patients with Wilson disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany. karl-heinz_weiss@med.uni-heidelberg.de
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Weiss
authors.forename: Florentine
authors.initials: F
authors.lastname: Thurik
authors.forename: Daniel Nils
authors.initials: DN
authors.lastname: Gotthardt
authors.forename: Mark
authors.initials: M
authors.lastname: Schäfer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Teufel
authors.forename: Franziska
authors.initials: F
authors.lastname: Wiegand
authors.forename: Uta
authors.initials: U
authors.lastname: Merle
authors.forename: Daniela
authors.initials: D
authors.lastname: Ferenci-Foerster
authors.forename: Andreas
authors.initials: A
authors.lastname: Maieron
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Heinz
authors.initials: H
authors.lastname: Zoller
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Reuner
authors.forename: Harald
authors.initials: H
authors.lastname: Hefter
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Trocello
authors.forename: Roderick H J
authors.initials: RH
authors.lastname: Houwen
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D000293:Adolescent; D000328:Adult; D001317:Austria; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005858:Germany; D006527:Hepatolenticular Degeneration / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014266:Trientine / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D002614:Chelating Agents; D010396:Penicillamine; D014266:Trientine
keywords: ATP7B; D-penicillamine; DPA; Metabolic Disorder; WD; Wilson disease; Wilson's Disease; Wilsons disease