Comparative analysis of clinical outcomes and safety profile of trientine and d-penicillamine in the management of Wilson’s disease: A systematic review and meta-analysis

Abstract

Introduction

Wilson disease (WD) is a rare metabolic disorder of copper metabolism, requiring life-long therapy, usually with D-penicillamine or trientine. This review compares their clinical effectiveness and safety.

Methodology

PubMed, Cochrane, Clinicaltrials.gov and WHO-ICTRP, along with other sources were searched. The cohorts and RCTs reporting WD patients of any age or stage, receiving either trientine or D-penicillamine, were included. The Mantel-Haenszel method along with either a fixed- or random-effects model was used for analysing dichotomous outcomes.

Results

Twenty-six cohorts and one RCT were included. The odds of having (1) treatment failures were greater with trientine (OR = 4.09; 95 %-CI:2.34–7.15; p < 0.00001); (2) adverse events were lesser with trientine (OR = 0.34; 95 %-CI:0.14–0.80; p = 0.01); (3) treatment discontinuation due to adverse events were lesser with trientine (OR = 0.30; 95 %-CI:0.21–0.43; p < 0.00001); and (4) symptomatic worsening were not significantly different (OR = 1.68; 95 %-CI:0.88–3.20; p = 0.012). Subgroup analysis within symptomatic worsening showed non-significant difference for neurological worsening (OR = 1.33; 95 %-CI:0.44–3.97; p = 0.61) and greater odds with trientine for hepatic worsening (OR = 2.45; 95 %-CI:1.17–5.12; p = 0.02). Trientine had similar serum copper parameters and slightly lower urinary copper-excretion rates compared to D-penicillamine. Trientine affected coagulation profiles but with no clinical association, and both treatments had similar effects on pregnancy outcomes.

Conclusion

Trientine therapy had significantly lower incidences of adverse events and treatment discontinuations, but higher incidences of treatment failure and neurological worsening compared to D-penicillamine. However, the low quality and indirectness of the evidence may have lowered the validity of the results. Studies directly comparing the clinical outcomes of both treatments are needed to establish more robust evidence.