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Meta-Analysis
. 2018 Sep 6;9(9):CD001127.
doi: 10.1002/14651858.CD001127.pub4.

Dornase alfa for cystic fibrosis

Connie Yang  1 , Mark Montgomery
Affiliations
Meta-Analysis

Dornase alfa for cystic fibrosis

Connie Yang et al. Cochrane Database Syst Rev. .

Update in

  • Dornase alfa for cystic fibrosis.
    Yang C, Montgomery M. Yang C, et al. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5. Cochrane Database Syst Rev. 2021. PMID: 33735508 Free PMC article.

Abstract

Background: Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.

Objectives: To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018.

Selection criteria: All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance.

Data collection and analysis: Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence.

Main results: The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash.

Authors' conclusions: There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.

PubMed Disclaimer

Conflict of interest statement

Dr Connie Yang has received support from Novartis to attend the Killarney Cystic Fibrosis Meeting in 2014 and the Pediatric Advisory Board.

Dr. Montgomery has no conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Adde 2004 {published data only}
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Amin 2011 {published data only}
    1. Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, et al. The effect of dornase alfa on ventilation in homogeneity in patients with cystic fibrosis. European Respiratory Journal 2011;37(4):806‐12. [CFGD Register: BD163b] - PubMed
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Castile 2009 {published data only}
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Dodd 2000 {published data only}
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Frederiksen 2006 {published data only}
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McCoy 1996 {published data only}
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Minasian 2010 {published data only}
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Quan 2001 {published data only}
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Ramsey 1993 {published data only}
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Ranasinha 1993 {published data only}
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Robinson 2000 {published data only}
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Robinson 2005 {published data only}
    1. Robinson T, Leung AN, Northway WH, Blankenberg FG, Chan F, Bloch DA, et al. Composite CT/PFT score: an outcome measure which markedly improves sensitivity to change in early cystic fibrosis lung disease [abstract]. Pediatric Pulmonology 2002;Suppl 24:298. [CFGD Register: BD106a]
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Shah 1995a {published data only}
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Suri 2001 {published data only}
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Wilmott 1996 {published data only}
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References to studies excluded from this review

Anderson 2009 {published data only}
    1. Anderson P, Morton J. Evaluation of two different timings of Pulmozyme nebulisation in relation to chest physiotherapy in children with cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S74, Abstract no: 299. [CFGD Register: BD162]
Bakker 2010 {published data only}
    1. Bakker EM, Volpi S, Salonini E, Mullinger B, Kroneberg P, Hop WCJ, et al. Efficacy of peripheral deposition of inhaled rhDNase in CF patients during a respiratory tract infection [abstract]. Journal of Cystic Fibrosis 2010;9 Supplement 1:S62, Abstract no: 239. [CFGD Register: BD155a]
    1. Bakker M, Volpi S, Salonini E, Wiel E, Merkus P, Sintnicolaas C, et al. Peripheral versus central deposition of inhaled rhdnase in children with cystic fibrosis [abstract]. Pediatric Pulmonology 2010;45(S33):306, Abstract no: 244. [CFGD Register: BD155b]
    1. Beukel‐Bakker M, Volpi S, Salonini E, Wiel‐Kooij EC, Sintnicolaas C, Hop WC, et al. Small airways response to dornase alfa improves using controlled inhalation: a randomized controlled trial in cystic fibrosis patients [abstract]. Journal of Cystic Fibrosis 2011;10 Supplement 1:S19, Abstract no: 75. [CFGD Register: BD155c]
Bilton 2011 {published data only}
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Bishop 2011 {published data only}
    1. Bishop JR, Erskine OJ, Middleton PG. Timing of dornase alpha inhalation does not affect the efficacy of an airway clearance regimen in adults with cystic fibrosis: a randomised crossover trial. Journal of physiotherapy 2011;57(4):223‐9. [CFGD Register: BD252a] - PubMed
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Bollert 1999 {published data only}
    1. Bollert FG, Paton JY, Marshall TG, Calvert J, Greening AP, Innes JA. Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n‐of‐1 trials. Scottish Cystic Fibrosis Group.. European Respiratory Journal 1999;13(1):107‐13. - PubMed
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Cimmino 2005 {published data only}
    1. Cimmino M, Nardone M, Cavaliere M, Plantulli A, Sepe A, Esposito V, et al. Dornase alfa as postoperative therapy in cystic fibrosis sinonasal disease. Archives of Otolaryngology ‐ Head and Neck Surgery 2005;131(12):1097‐101. - PubMed
Craig 2013 {published data only}
    1. Craig T. Pulmozyme in cystic fibrosis with sinusitis. clinicaltrials.gov/ct2/show/NCT01155752 (accessed 14 April 2015).
Dab 2000 {published data only}
    1. Dab A, Malfroot D, Baran EM, App M, Coffiner M, Nagy AM. Randomized multicentric double blind study of safety and efficacy of Nacystelyn DPI versus placebo in rhDNase treated cystic fibrosis patients [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(3):A72.
    1. Malfroot A, Dab I, Baran D, App EM, Coffiner M, Nagy AM. Randomised multicentric double blind study of tolerability and efficacy of a DPI Nacystelyn versus placebo in cystic fibrosis patients treated by rhDNase for at least 3 months [abstract]. Proceedings of the 13th International Cystic Fibrosis Congress; 2000 June 4‐8; Stockholm, Sweden. 2000:146.
    1. Malfroot A, Dab I, Baran D, App EM, Coffiner M, Nagy AM. Randomized multicentric double blind study of tolerability and efficacy of a DPI Nacystelyn versus placebo in cystic fibrosis patients treated by rhDNase for at least 3 months [abstract]. Pediatric Pulmonology 1999;Suppl 19:244.
Diot 2009 {published data only}
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Elkins 2006 {published data only}
    1. Elkins MR, Bye PTP. Comparison of Pari LC‐Star and ‐Plus nebulisers delivering 2.5mg recombinant human deoxyribonuclease (rhDNase) [abstract]. Journal of Cystic Fibrosis 2006;5 Suppl:S42.
EUCTR2006‐002098‐30‐NL {published data only}
    1. EUCTR2006‐002098‐30‐NL. Efficacy of inhaled rhDNase in mechanically ventilated pediatric patients with an atelectasis ‐ rhDNase in ventilated pediatric patients. apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2006‐002098‐30‐NL (first received 01 June 2006).
EUCTR2007‐000935‐25‐NL {published data only}
    1. EUCTR2007‐000935‐25‐NL. Peripheral targeting of inhaled rhDNase in stable CF patients. apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2007‐000935‐25‐NL (first received 02 April 2007).
Fitzgerald 2005 {published data only}
    1. Fitzgerald DA, Hilton J, Jepson B, Smith L. A crossover, randomized, controlled trial of dornase alfa before versus after physiotherapy in cystic fibrosis. Pediatrics 2005;116(4):e549‐54. [CFGD Register: BD102b] - PubMed
    1. Fitzgerald DA, Hilton J, Smith L, Jepson B. Is dornase alfa (pulmozyme) more effective before or after physiotherapy? A cross‐over, randomised placebo controlled trial [abstract]. Pediatric Pulmonology 2001;Suppl 22:309‐10. [CFGD Register: BD102a]
Freemer 2010 {published data only}
    1. Genentech Inc. A study of Pulmozyme® (dornase alpha) in 3‐ to 5‐year‐old patients with cystic fibrosis. clinicaltrials.gov/ct2/show/NCT00680316 (accessed 14 April 2015). [clinicaltrials.gov: NCT00680316]
Furuya 2001 {published data only}
    1. Furuya ME, Lezana‐Fernandez JL, Vargas MH, Hernandez‐Sierra JF, Ramirez‐Figueroa JL. Efficacy of human recombinant DNase in pediatric patients with cystic fibrosis. Archives of Medical Research 2001;32(1):30‐4. - PubMed
Genentech 2010 {published data only}
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Griese 1997 {published data only}
    1. Griese M, App EM, Derouix A, Burkert A, Schams A. Recombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum. Pulmonary Pharmacology and Therapeutics 1997;10(1):21‐7. - PubMed
Hagelberg 2008 {published data only}
    1. Hagelberg M, Dooley MJ, Poole SG, Leung D, Bailey M, Finlayson F, et al. Direct dispensing of dornase alpha improves adherence and lung function in cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2008;7(Suppl 2):S27.
Heijerman 1995 {published data only}
    1. Heijerman HGM, Rossem RN, Bakker W. Effect of rhDNase on lung function and quality of life in adult cystic fibrosis patients. The Netherlands Journal of Medicine 1995;46(6):293‐7. [CFGD Register: BD43] - PubMed
Hubbard 1992 {published data only}
    1. Hubbard RC, McElvaney NG, Birrer P, Shak S, Robinson WW, Jolley C, et al. A preliminary study of aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. New England Journal of Medicine 1992;326(12):812‐5. - PubMed
Johnson 2006 {published data only}
    1. Johnson JC, Waldrep JC, Dhand R. Aerosol delivery of recombinant human DNase 1. Comparison of a vibrating mesh nebulizer with a jet nebulizer [abstract]. American Thoracic Society International Conference; 2006 May 19‐24; California, USA. 2006:A82.
Kelijo 2001 {published data only}
    1. Kelijo DJ, Giroir B, Jialal I. Circulating tumor necrosis factor‐alpha and IL‐6 levels in patients with cystic fibrosis and mild lung disease: effects of Dnase and alpa‐tocopherol therapy. Unpublished article 2001, issue Obtained 2014. [CFGD Register: GN87b]
King 1997 {published data only}
    1. King M, Dasgupta B, Tomkiewicz RP, Brown NE, Pulmonary Research Group. Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I. American Journal of Respiratory and Critical Care Medicine 1997;156(1):173‐7. - PubMed
Lahiri 2012 {published data only}
    1. Lahiri T. Nasally Delivered Pulmozyme for Sinusitis in Cystic Fibrosis. https://clinicaltrials.gov/ct2/show/NCT00416182?term=nct00416182&rank=1 accessed 14 April 2015.
    1. Lahiri T, Herrington H, Diehl S, Landrigan G. The effect of intranasal dornase alfa on chronic sinusitis in patients with cystic fibrosis: a pilot study.. Pediatric Pulmonology 2012;S35:354.
Laube 2005 {published data only}
    1. Laube BL, Geller DE, Lin TC, Dalby RN, Diener‐West M, Zeitlin PL. Positive expiratory pressure changes aerosol distribution in patients with cystic fibrosis. Respiratory Care 2005;50(11):1438‐44. - PubMed
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Mainz 2011 {published data only}
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