Adult

Cystic Fibrosis

Guidelines

Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187:680-9. This document offers graded recommendations for medication use according to patient age and severity of lung disease. It also summarizes areas of uncertainty.

PMID: 23540878

Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med 2009; 180:802-8. This document offers graded recommendations for management of exacerbations, but is most noteworthy for highlighting the lack of evidence guiding many fundamental aspects of care.

PMID: 19729669

Floto RA, Olivier KN, Saiman L, et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. Thorax. 2016;7:88-90.

A summary of evidence-based recommendations regarding screening, diagnosis, therapeutics, and transplant considerations for patients with cystic fibrosis.

PMID: 26678435

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Therapeutics- Inhaled Medications

Balfour-Lynn IM, Lees B, Hall P, et al. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med 2006; 173:1356-62. This study of 171 children and adults with mean baseline FEV1 of 76% predicted found no difference in time to 1st exacerbation, or use of rescue bronchodilators and antibiotics over the first 6 months of withdrawing inhaled steroid. These results suggest that many CF patients may be able to safely discontinue inhaled steroids.

PMID: 16556691

Therapeutics- CFTR Modulators

Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-72. The first study to show a substantial benefit from a therapy targeting the underlying cause of clinical CF, this trial showed an absolute increase in predicted FEV1 of 10% in patients with at least one G551D-CFTR mutation receiving ivacaftor, a CFTR potentiator, compared to a small FEV1 decline in the placebo group, over a study period of approximately six months.

PMID: 22047557

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Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015; 373: 220-231. This reports on pooled data from two multicenter, double-blind, placebo-controlled 24-week studies assessing the effect of ivacaftor (potentiator) in combination with two different doses of lumacaftor (corrector)  in patients with homozygous Phe508del CFTR mutations. The treatment group had a mean improvement in percent predicted FEV1 ranging from 2.4 to 4.0% (p < .001), as well as a 30% reduction in the risk of exacerbation. Adverse events were similar between groups. It remains to be seen whether these benefit persist or accumulate over time.

PMID: 25981758

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Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med. 2017; 377:2013-23. Randomized, double-blind, multicenter, placebo-controlled trial of nearly 500 patients 12 years and older homozygous for the Phe508 del mutation found combination therapy with tezacaftor and ivacaftor improved the percent predicted FEV1(4 points absolute and 6.8 points relative; p<0.001) after 24 weeks of treatment. The exacerbation rate was 35% lower in the treatment group (p=0.005).

PMID: 29099344

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Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-Ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017; 377:2024-35. This randomized, double-blind, placebo-controlled, crossover trial evaluated ivacaftor alone or in combination with tezacaftor in 248 cystic fibrosis patients heterozygous for the CFTR Phe508del mutation. Compared to placebo, tezacaftor-ivacaftor and ivacaftor alone improved the percent predicted FEV1 by 6.8 points and 4.7 points, respectively (p<0.001). Scores on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised significantly favored the active treatment.

PMID: 29099333

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Last Reviewed: May 2018