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Enzyme replacement therapy for Anderson-Fabry disease.
Cochrane Database Syst Rev. 2016 Jul 25; 7:CD006663.CD

Abstract

BACKGROUND

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers.This is an update of a Cochrane review first published in 2010, and previously updated in 2013.

OBJECTIVES

To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease.

SEARCH METHODS

We searched the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 08 July 2016). We also searched 'Clinical Trials' on The Cochrane Library, MEDLINE, Embase and LILACS (date of the most recent search: 24 September 2015).

SELECTION CRITERIA

Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease.

DATA COLLECTION AND ANALYSIS

Two authors selected relevant trials, assessed methodological quality and extracted data.

MAIN RESULTS

Nine trials comparing either agalsidase alfa or beta in 351 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores measured by the Brief Pain Inventory severity, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval -3.79 to -0.41; at up to five months, mean difference -1.90 (95% confidence interval -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% confidence interval -3.66 to -0.34). There was a significant difference in the Brief Pain Inventory pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% confidence interval -3.92 to -0.28) but not at other time points. Death was not an outcome in either of the trials.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% confidence interval -2.09 to -1.31); heart, mean difference -0.90 (95% confidence interval -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% confidence interval -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only two trials compared agalsidase alfa to agalsidase beta. One of them showed no significant difference between the groups regarding adverse events, risk ratio 0.36 (95% confidence interval 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; (95% confidence interval 0.03 to 2.57).Two trials compared different dosing schedules of agalsidase alfa. One of them involved three different doses (0.2 mg/kg every two weeks; 0.1 mg/kg weekly and; 0.2 mg/kg weekly), the other trial evaluated two further doses to the dosage schedules: 0.4 mg/kg every week and every other week. Both trials failed to show significant differences with various dosing schedules on globotriaosylceramide levels. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores.One trial comparing agalsidase alfa to agalsidase beta showed no significant difference for any adverse events such as dyspnoea and hypertension.The methodological quality of the included trials was generally unclear for the random sequence generation and allocation concealment.

AUTHORS' CONCLUSIONS

Trials comparing enzyme replacement therapy to placebo show significant improvement with enzyme replacement therapy in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior or the optimal dose or frequency of enzyme replacement therapy. With regards to safety, adverse events (i.e., rigors, fever) were more significant in the agalsidase beta as compared to placebo. The long-term influence of enzyme replacement therapy on risk of morbidity and mortality related to Anderson-Fabry disease remains to be established. This review highlights the need for continued research into the use of enzyme replacement therapy for Anderson-Fabry disease.

Authors+Show Affiliations

Department of Anaesthesiology, Botucatu Medical School, UNESP - Univ Estadual Paulista, Distrito de Rubião Júnior, s/n, Botucatu, Brazil, 18603-970.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

27454104

Citation

El Dib, Regina, et al. "Enzyme Replacement Therapy for Anderson-Fabry Disease." The Cochrane Database of Systematic Reviews, vol. 7, 2016, p. CD006663.
El Dib R, Gomaa H, Carvalho RP, et al. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2016;7:CD006663.
El Dib, R., Gomaa, H., Carvalho, R. P., Camargo, S. E., Bazan, R., Barretti, P., & Barreto, F. C. (2016). Enzyme replacement therapy for Anderson-Fabry disease. The Cochrane Database of Systematic Reviews, 7, CD006663. https://doi.org/10.1002/14651858.CD006663.pub4
El Dib R, et al. Enzyme Replacement Therapy for Anderson-Fabry Disease. Cochrane Database Syst Rev. 2016 Jul 25;7:CD006663. PubMed PMID: 27454104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme replacement therapy for Anderson-Fabry disease. AU - El Dib,Regina, AU - Gomaa,Huda, AU - Carvalho,Raíssa Pierri, AU - Camargo,Samira E, AU - Bazan,Rodrigo, AU - Barretti,Pasqual, AU - Barreto,Fellype C, Y1 - 2016/07/25/ PY - 2016/7/26/entrez PY - 2016/7/28/pubmed PY - 2016/9/23/medline SP - CD006663 EP - CD006663 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 7 N2 - BACKGROUND: Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers.This is an update of a Cochrane review first published in 2010, and previously updated in 2013. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 08 July 2016). We also searched 'Clinical Trials' on The Cochrane Library, MEDLINE, Embase and LILACS (date of the most recent search: 24 September 2015). SELECTION CRITERIA: Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. DATA COLLECTION AND ANALYSIS: Two authors selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: Nine trials comparing either agalsidase alfa or beta in 351 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores measured by the Brief Pain Inventory severity, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval -3.79 to -0.41; at up to five months, mean difference -1.90 (95% confidence interval -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% confidence interval -3.66 to -0.34). There was a significant difference in the Brief Pain Inventory pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% confidence interval -3.92 to -0.28) but not at other time points. Death was not an outcome in either of the trials.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% confidence interval -2.09 to -1.31); heart, mean difference -0.90 (95% confidence interval -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% confidence interval -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only two trials compared agalsidase alfa to agalsidase beta. One of them showed no significant difference between the groups regarding adverse events, risk ratio 0.36 (95% confidence interval 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; (95% confidence interval 0.03 to 2.57).Two trials compared different dosing schedules of agalsidase alfa. One of them involved three different doses (0.2 mg/kg every two weeks; 0.1 mg/kg weekly and; 0.2 mg/kg weekly), the other trial evaluated two further doses to the dosage schedules: 0.4 mg/kg every week and every other week. Both trials failed to show significant differences with various dosing schedules on globotriaosylceramide levels. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores.One trial comparing agalsidase alfa to agalsidase beta showed no significant difference for any adverse events such as dyspnoea and hypertension.The methodological quality of the included trials was generally unclear for the random sequence generation and allocation concealment. AUTHORS' CONCLUSIONS: Trials comparing enzyme replacement therapy to placebo show significant improvement with enzyme replacement therapy in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior or the optimal dose or frequency of enzyme replacement therapy. With regards to safety, adverse events (i.e., rigors, fever) were more significant in the agalsidase beta as compared to placebo. The long-term influence of enzyme replacement therapy on risk of morbidity and mortality related to Anderson-Fabry disease remains to be established. This review highlights the need for continued research into the use of enzyme replacement therapy for Anderson-Fabry disease. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27454104/Enzyme_replacement_therapy_for_Anderson_Fabry_disease_ L2 - https://doi.org/10.1002/14651858.CD006663.pub4 DB - PRIME DP - Unbound Medicine ER -