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

Chen JC, Chuang CH, Wang JD, Wang CW - J Med Biol Eng (2015)

Bottom Line: 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.These were analyzed in terms of data on effectiveness, adverse effects, and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Information Engineering, Asia University, Taichung, 41354 Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

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
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Fig6: 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

Mentions: Data on combination therapy safety, including adverse effects and mortality, are presented in Table 4. Since the first combination therapy type was clearly the most common, we collapsed the other six to create a workable balance between sample sizes. Note that we split the statistics for one study [11] into two parts because the patients were treated with two different combination therapies. Since some of the studies in the sample did not specifically describe adverse reactions for different phenotypes, the numbers of TBs for different phenotypes and for overall adverse effects are not equal. Of the 271 TBs listed in Table 4, 97 resulted in adverse reactions, an overall adverse effect rate of 35.8 % (95 % CI 30.1–41.5 %). The percentage for patients in the hepatic category was 41.7 % (95 % CI 31.1–52.2 %) and that for those in the neurological category was 26.3 % (95 % CI 12.3–40.3 %), not significantly different (p = 0.84), perhaps due to the small sample size. Results from our analysis of inter-studies on adverse effect rates are presented in Fig. 6, with the number of events noted as the number of TBs presenting adverse effects. The data indicate that the combination therapies resulted in greater relative risk compared to those for the TETA (RR: 1.67, 95 % CI 1.04–2.69) and Zn (RR: 2.25, 95 % CI 1.36–3.73) monotherapies [16], but not that for the DPA monotherapy [37] (RR: 1.10, 95 % CI 0.87–1.38). Statistically significant differences were not noted for correlation and difference measures between different combination therapy types and overall adverse effects (χ2(1) = 0.938, p = 0.333 and Z = −0.968, p = 0.166).Table 4


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

Chen JC, Chuang CH, Wang JD, Wang CW - J Med Biol Eng (2015)

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4666238&req=5

Fig6: 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
Mentions: Data on combination therapy safety, including adverse effects and mortality, are presented in Table 4. Since the first combination therapy type was clearly the most common, we collapsed the other six to create a workable balance between sample sizes. Note that we split the statistics for one study [11] into two parts because the patients were treated with two different combination therapies. Since some of the studies in the sample did not specifically describe adverse reactions for different phenotypes, the numbers of TBs for different phenotypes and for overall adverse effects are not equal. Of the 271 TBs listed in Table 4, 97 resulted in adverse reactions, an overall adverse effect rate of 35.8 % (95 % CI 30.1–41.5 %). The percentage for patients in the hepatic category was 41.7 % (95 % CI 31.1–52.2 %) and that for those in the neurological category was 26.3 % (95 % CI 12.3–40.3 %), not significantly different (p = 0.84), perhaps due to the small sample size. Results from our analysis of inter-studies on adverse effect rates are presented in Fig. 6, with the number of events noted as the number of TBs presenting adverse effects. The data indicate that the combination therapies resulted in greater relative risk compared to those for the TETA (RR: 1.67, 95 % CI 1.04–2.69) and Zn (RR: 2.25, 95 % CI 1.36–3.73) monotherapies [16], but not that for the DPA monotherapy [37] (RR: 1.10, 95 % CI 0.87–1.38). Statistically significant differences were not noted for correlation and difference measures between different combination therapy types and overall adverse effects (χ2(1) = 0.938, p = 0.333 and Z = −0.968, p = 0.166).Table 4

Bottom Line: 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.These were analyzed in terms of data on effectiveness, adverse effects, and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Information Engineering, Asia University, Taichung, 41354 Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus