Transition from zinc salts to trientine tetrahydrochloride in a cohort of adult patients with Wilson disease: the ZICUP study

Wilson disease (WD) treatment aims to reduce copper accumulation in the liver and brain. Zinc salts (ZS) are often associated with gastrointestinal side effects, poor adherence, and reduced efficacy. Copper chelators, such as trientine tetrahydrochloride (TETA4), offer an alternative for patients who are intolerant or unresponsive to ZS. This observational study assesses the long-term efficacy and safety of switching from ZS to TETA4 in twenty WD patients (15 hepatic, 5 hepato-neurological) from the French WD Registry. Treatment goals included normalization of aminotransferases, stabilization or improvement of the liver (APRI, liver stiffness and liver ultrasonography; US) and the neurological (Unified Wilson’s Disease Rating Scale; UWDRS) involvement, Clinical Global Impression (CGI) severity scale, and achievement of copper balance targets. Assessments were performed at baseline and every 6 months for 3 years. Adverse events were recorded throughout the follow-up. The results revealed that the main reasons for switching were gastrointestinal intolerance and loss of efficacy with ZS; 60% had elevated ALT at baseline. TETA4 was initiated at a median dose of 412.5 mg (360–450) and titrated up to 750 mg/day (600–900 mg) to achieve the treatment goals. Over 3 years, no changes were observed in ALT, APRI, liver US, UWDRS and CGI scores. TETA4 was well tolerated. In conclusion, transitioning from ZS to TETA4 maintained clinical stability and adherence with a favorable safety profile. Dose adjustments suggest conversion ratios of ~1:6 elemental zinc.