Trientine tetrahydrochloride well tolerated in patients with Wilson disease: Lancet

A new study published in The Lancet Gastroenterology & Hepatology suggests that trientine tetrahydrochloride (TETA4) was as effective and well tolerated as an oral maintenance medication for adults with Wilson disease compared to penicillamine.

Wilson disease is a genetic copper transport abnormality. Trientine is recommended for people who are intolerant to penicillamine, whereas penicillamine is used therapeutically to restore copper balance. In order to compare penicillamine with trientine tetrahydrochloride for maintenance treatment in individuals with Wilson disease, Michael L. Schilsky and colleagues carried out this study.

At 15 healthcare facilities in nine countries, researchers conducted this randomized, phase 3 experiment. Patients with stable Wilson disease who had penicillamine treatment for at least a year were included, ranging in age from 18 to 75. Patients were evaluated clinically by site investigators over a 12-week period, as well as according to predetermined thresholds for alanine aminotransferase, 24 hour urine copper excretion, and serum non-ceruloplasmin-bound copper. Stable patients were randomly randomized (1:1) to either continue receiving the maintenance twice-daily oral penicillamine dosage or to centrally switch mg-for-mg to oral TETA4. NCC by speciation test was the main outcome, which was evaluated 24 weeks after randomization. All patients who took at least one dosage of trial therapy had their safety evaluated.

The key findings of this study were:

1. 77 individuals underwent screening between June 4, 2018, and March 10, 2020. 

2. After 24 weeks, the lower limit of the 95% confidence interval for the mean difference in serum NCC by speciation test between the penicillamine group and the TETA4 group was -9 g/L, falling within the predetermined non-inferiority margin.

3. When compared to penicillamine, urinary copper excretion was reduced with TETA4 at 24 weeks.

4. In terms of NCC by speciation test, TETA4 was still non-inferior to penicillamine at 48 weeks.

5. Urinary copper excretion at 48 weeks for well-treated patients in both study groups remained below predicted limits, and the mean difference was not substantially different.

6. Clinical stability was established in 100% of all individuals at 24 and 48 weeks by masked clinical adjudication of stability assessed by three independent doctors, which was consistent with the stability seen with the NCC by speciation test.

7. At weeks 24 and 48, neither the Clinical Global Impression of Change nor the Unified Wilson Disease Rating Scale (neurological evaluation) showed any significant deviations from the pre-randomization baseline.

8. The mean change in serum total caeruloplasmin from baseline to 24 weeks was 1 mg/L (-19 2 to 22 8) with penicillamine and -2 mg/L (-6 1 to 1 7).

9. The mean change in serum total copper from baseline to 24 weeks was 17 6 g/L with penicillamine and -6 3 g/L (-34 7 to 22 1).

Reference: 

Schilsky, M. L., Czlonkowska, A., Zuin, M., Cassiman, D., Twardowschy, C., Poujois, A., Gondim, F. de A. A., Denk, G., Cury, R. G., Ott, P., Moore, J., Ala, A., D'Inca, R., Weiss, K. H., To, U., … Cosgrove, J. (2022). Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. In The Lancet Gastroenterology & Hepatology. Elsevier BV. https://doi.org/10.1016/s2468-1253(22)00270-9