Studies that assessed D-penicillamine, trientine, tetrathiomolybdate or zinc monotherapy in patients with an established diagnosis of Wilson disease were eligible. Case reports or series and studies that did not evaluate anticopper therapy were excluded. Clinical outcomes had to be specified as asymptomatic, improved, unchanged, deteriorated or dead and determined after more than three months of follow-up. Outcomes had to be reported for all patients exposed to a single anticopper drug and relate to their initial presentation.
Most studies were retrospective or prospective cohort studies. They evaluated D-penicillamine (doses ranging from 0.6 to 1.8g/day) and elemental zinc (150 to 275mg/day) alone or together. The one randomised controlled trial (RCT) compared D-penicillamine (1 to 1.5g/day) with zinc (0.6 to 0.8g/day). There were some inconsistencies in reporting of doses. Most studies included presymptomatic patients or combinations of presymptomatic, hepatic and neuralgic patients. Mean patient ages at diagnosis were 14 years (range 1.5 to 52 years, D-penicillamine) and 12.5 (range three to 39, zinc). Outcomes were assessed after a mean of 64 months (D-penicillamine) or 81 months (zinc) with a range from three to 323 months.
The authors did not state how many reviewers performed study selection.