Combination Therapy Using Chelating Agent and Zinc for Wilson's Disease

Abstract

There is no clear international consensus regarding the optimal medication therapy for treating Wilson's disease (WD). This study systematically reviews the effectiveness of various medication therapies in common use, specifically focusing on preliminary findings concerning the combination of a chelating agent and zinc. A systematic PubMed search was executed to locate original studies on the effectiveness of commonly used medications for WD published between January 1989 and August 2014. The results were used to conduct a systematic review of studies on combination therapies. A total of 17 combination therapy studies involving 1056 patients were reviewed. These were analyzed in terms of data on effectiveness, adverse effects, and mortality. Results from a pooled analysis indicate that combination therapies for hepatic patients were significantly less effective than the same therapies for neurological manifestations (47.1 vs. 78.6 %; pooled relative risk ratio (RR): 0.63, 95 % confidence interval CI 0.43-0.94; p = 0.02). Data from a subgroup analysis show that the combination therapy of penicillamine plus zinc sulfate resulted in a significantly higher mortality rate compared to all other combination therapy types (16.3 vs. 4.7 %; RR: 3.51, 95 % CI 1.54-8.00; p < 0.001). The use of combination therapies involving zinc and a chelator should be carefully monitored with close clinical observations and frequent biochemical tests, especially for WD patients with hepatic manifestations.

Keywords: Biomedical informatics; Combination therapy; Effectiveness; Safety; Wilson’s disease.

Fig. 1

Flow chart of included and excluded studies for this review

Fig. 2

Forest plot of 17 included studies measuring relative risk of pooled effectiveness following combination therapy compared to DPA monotherapy [15]

Fig. 3

Forest plot of 17 included studies measuring relative risk of pooled effectiveness following combination therapy compared to TETA monotherapy [37]

Fig. 4

Forest plot of 17 included studies measuring relative risk of pooled effectiveness following combination therapy compared to Zn monotherapy [16]

Fig. 5

Forest plot of studies on combination therapies for hepatic phenotype versus neurological phenotype examining relative risk of effectiveness

Fig. 6

Forest plot of 17 included studies measuring relative risk of pooled adverse effects following combination therapy compared to a DPA, b TETA, and c Zn monotherapies

Fig. 7

Forest plot of 17 included studies measuring relative risk of pooled mortality following combination therapy compared to pooled mortality of four most commonly used medications