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Deoxyribonuclease for cystic fibrosis.

Abstract

BACKGROUND

Recombinant human deoxyribonuclease is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis.

OBJECTIVES

To determine whether the use of recombinant human deoxyribonuclease in cystic fibrosis is associated with improved mortality and morbidity as compared to placebo and to identify any adverse events associated with its use. To compare the efficacy of recombinant human deoxyribonuclease with other mucolytics.

SEARCH STRATEGY

The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstracts from conferences. The company producing recombinant human deoxyribonuclease was also contacted. Date of the most recent search of the Group's specialised register: November 1999.

SELECTION CRITERIA

All randomised and quasi-randomised trials where recombinant human deoxyribonuclease was compared to either placebo, standard therapy or another mucolytic for any duration, dose regimen and age of patient with cystic fibrosis of any disease severity.

DATA COLLECTION AND ANALYSIS

Trials were independently assessed for inclusion criteria, methodological quality and data extraction by the two reviewers. Comparisons were between recombinant human deoxyribonuclease and placebo and recombinant human deoxyribonuclease and other mucolytics. The following outcomes were recorded: Mean % change from baseline in forced vital capacity (FVC), forced expiratory voloume at one second (FEV1) and weight, mean number of respiratory tract exacerbations, days intravenous and oral antibiotics used, mean number of days as inpatient, number of deaths, adverse events and the cost of therapy.

MAIN RESULTS

Seven primary clinical trials were identified, totalling 1710 patients. Two further studies examined the health care cost of patients from one of the clinical trials. No eligible studies compared recombinant human deoxyribonuclease to another mucolytic. Five trials presented outcomes at up to one month, one at three months and one at six months. No reduction in mortality for treated patients was identified (Relative Risk (RR) at six month 1.01, 95%Confidence Interval (CI) 0.09, 11.11). Lung function improved to a greater extent in the treated groups (at six months Weighted Mean Difference (WMD) FEV1 5.7, 95%CI 4.18, 7.23, at three months 7.3, 95%CI 4.04, 10.65). Pooled data from the five trials of up to one month gave WMD 9.2 95%CI 0.93, 17. 6 although there was significant heterogeneity). Recombinant human deoxyribonuclease was well tolerated with no excess of serious adverse events (RR haemoptysis 0.89, 95%CI 0.54, 1.45, pneumothorax 0.97 95%CI 0.19, 4.96). Voice alteration was, however, reported more frequently in the treated groups (RR 2.33 95%CI 1.38, 3.93). No study analysed our pre-defined outcome measure for respiratory exacerbations and insufficient data was available to analyse differences in antibiotic treatment, inpatient stay and quality of life.

REVIEWER'S CONCLUSIONS

Studies are of insufficient duration to identify a reduction in mortality or number of respiratory exacerbations. Further trials are required to answer these important questions. Recombinant human deoxyribonuclease therapy is associated with an improvement in lung function after six months treatment, but it is not possible to assess whether this effect on lung function is sustained in the long-term. No studies were identified that compared recombinant human deoxyribonuclease to another mucolytic.

Authors+Show Affiliations

Northwick Park Hospital, Watford Road, Harrow, Middlesex, UK, HA1 3UJ.No affiliation info available

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

10796748

Citation

Kearney, C E., and C E. Wallis. "Deoxyribonuclease for Cystic Fibrosis." The Cochrane Database of Systematic Reviews, 2000, p. CD001127.
Kearney CE, Wallis CE. Deoxyribonuclease for cystic fibrosis. Cochrane Database Syst Rev. 2000.
Kearney, C. E., & Wallis, C. E. (2000). Deoxyribonuclease for cystic fibrosis. The Cochrane Database of Systematic Reviews, (2), CD001127.
Kearney CE, Wallis CE. Deoxyribonuclease for Cystic Fibrosis. Cochrane Database Syst Rev. 2000;(2)CD001127. PubMed PMID: 10796748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deoxyribonuclease for cystic fibrosis. AU - Kearney,C E, AU - Wallis,C E, PY - 2000/5/5/pubmed PY - 2000/7/8/medline PY - 2000/5/5/entrez SP - CD001127 EP - CD001127 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 2 N2 - BACKGROUND: Recombinant human deoxyribonuclease is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. OBJECTIVES: To determine whether the use of recombinant human deoxyribonuclease in cystic fibrosis is associated with improved mortality and morbidity as compared to placebo and to identify any adverse events associated with its use. To compare the efficacy of recombinant human deoxyribonuclease with other mucolytics. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstracts from conferences. The company producing recombinant human deoxyribonuclease was also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised and quasi-randomised trials where recombinant human deoxyribonuclease was compared to either placebo, standard therapy or another mucolytic for any duration, dose regimen and age of patient with cystic fibrosis of any disease severity. DATA COLLECTION AND ANALYSIS: Trials were independently assessed for inclusion criteria, methodological quality and data extraction by the two reviewers. Comparisons were between recombinant human deoxyribonuclease and placebo and recombinant human deoxyribonuclease and other mucolytics. The following outcomes were recorded: Mean % change from baseline in forced vital capacity (FVC), forced expiratory voloume at one second (FEV1) and weight, mean number of respiratory tract exacerbations, days intravenous and oral antibiotics used, mean number of days as inpatient, number of deaths, adverse events and the cost of therapy. MAIN RESULTS: Seven primary clinical trials were identified, totalling 1710 patients. Two further studies examined the health care cost of patients from one of the clinical trials. No eligible studies compared recombinant human deoxyribonuclease to another mucolytic. Five trials presented outcomes at up to one month, one at three months and one at six months. No reduction in mortality for treated patients was identified (Relative Risk (RR) at six month 1.01, 95%Confidence Interval (CI) 0.09, 11.11). Lung function improved to a greater extent in the treated groups (at six months Weighted Mean Difference (WMD) FEV1 5.7, 95%CI 4.18, 7.23, at three months 7.3, 95%CI 4.04, 10.65). Pooled data from the five trials of up to one month gave WMD 9.2 95%CI 0.93, 17. 6 although there was significant heterogeneity). Recombinant human deoxyribonuclease was well tolerated with no excess of serious adverse events (RR haemoptysis 0.89, 95%CI 0.54, 1.45, pneumothorax 0.97 95%CI 0.19, 4.96). Voice alteration was, however, reported more frequently in the treated groups (RR 2.33 95%CI 1.38, 3.93). No study analysed our pre-defined outcome measure for respiratory exacerbations and insufficient data was available to analyse differences in antibiotic treatment, inpatient stay and quality of life. REVIEWER'S CONCLUSIONS: Studies are of insufficient duration to identify a reduction in mortality or number of respiratory exacerbations. Further trials are required to answer these important questions. Recombinant human deoxyribonuclease therapy is associated with an improvement in lung function after six months treatment, but it is not possible to assess whether this effect on lung function is sustained in the long-term. No studies were identified that compared recombinant human deoxyribonuclease to another mucolytic. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/10796748/Deoxyribonuclease_for_cystic_fibrosis_ L2 - https://doi.org/10.1002/14651858.CD001127 DB - PRIME DP - Unbound Medicine ER -