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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Middleton PG, Mall MA, Drevinek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381:1809-19. Randomized, double-blind, placebo-controlled trial of 403 patients 12 years or older with single Phe508del allele found elexacaftor-tezacaftor-ivacaftor improved percent predicted FEV1 by 14% at 24 weeks compared to placebo (p<0.001). Rate of exacerbation was 63% lower in the treatment group (p<0.001).

PMID: 31697873

Heijerman HGM, McKone EF, Downey DG et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940-48. Randomized, double-blind trial randomized 113 participants age 12 years or older to elexacaftor-tezacaftor-ivacaftor vs. tezacaftor-ivacaftor and found percent predicted FEV1 improved 10.0 points in the triple therapy group after 4 weeks. Triple combination therapy was well tolerated, although the trial was of short duration.

PMID: 31679946