Prospective Study to Assess Long-Term Outcomes of Chelator-Based Treatment With Trientine Dihydrochloride in Patients With Wilson Disease.

Background and Aims: Wilson disease is an inherited disorder of copper metabolism affecting mainly the liver and brain. Trientine dihydrochloride (TETA-2HCl) is approved for the treatment of Wilson disease in patients (≥ 5 years) intolerant to D-penicillamine therapy. This study assessed the long-term outcomes of treatment with TETA-2HCl in Wilson disease patients. Methods: In this Phase 2, prospective study, patients continued their treatment of TETA-2HCl 300 mg (200 mg trientine base) for 12 months (July 2015-April 2017) at one center in Germany. Primary outcomes were the safety and efficacy of TETA-2HCl treatment; Biomarkers of copper metabolism; and the course of hepatic and neurologic disease. Results: Overall, 51 patients contributed data. Almost all patients (50 [98.0%]) were considered responders (rating of ≤ 4 at the 12-month visit); Unified Wilson Disease Rating Scale scores improved throughout the study from a mean (standard deviation) of 11.3 (24.31) at Baseline to 8.8 (22.86) at Month 12. Biochemical assessments of liver parameters (transaminases, liver synthesis) as well as markers of copper metabolism (24-h urinary copper, non-ceruloplasmin bound copper (NCC)) showed improved or stable disease throughout the study. Treatment-emergent adverse events were reported in five (9.6%) patients. No patients withdrew from treatment due to adverse events, and no serious adverse events were considered to be treatment-related. Conclusions: This study demonstrated that treatment with TETA-2HCl was effective and well tolerated in hepatic and neurologic disease manifestations. Additionally, improvement in neurological symptoms was reported throughout the trial, suggesting that improvements may be reported for an extended period after initiation of therapy.