Topic
Cystic fibrosis
Mucolytics, inhaled antibiotics, and the CFTR modulators.
What the evidence shows
CFTR modulators corrected the basic defect, and the sweat chloride fall in the first positive trial made that literally measurable (STRIVE). Ivacaftor gave a 10-point FEV1 gain but only to the 4% of patients carrying G551D.
Triple therapy extended that to roughly 90% of patients. Elexacaftor-tezacaftor-ivacaftor produced a 14-point improvement in predicted FEV1 and cut exacerbations by 63% in genotypes where earlier modulators had failed (VX17-445-102) — the trial that changed the trajectory of the disease. A once-daily successor is non-inferior on lung function and reduces treatment burden (SKYLINE).
The field's question is now what to stop. In patients on triple modulator therapy with well-preserved lung function, discontinuing hypertonic saline or dornase alfa for six weeks was non-inferior to continuing (SIMPLIFY). Six weeks is short and the participants were well, so this licenses deprescribing in stable patients rather than in everyone.
CFTR modulators
| Trial | Year | Therapy | Effect | Finding |
|---|---|---|---|---|
| SKYLINE | 2025 | Vanzacaftor/tezacaftor/deutivacaftor | The once-daily triple matched the twice-daily standard on lung function | |
| VX17-445-102 | 2019 | Elexacaftor/tezacaftor/ivacaftor | Triple modulator therapy gave a 14-point FEV1 gain to the 90% of CF patients with a single Phe508del allele | |
| STRIVE | 2011 | Ivacaftor | Ivacaftor produced a 10-point FEV1 gain in G551D cystic fibrosis — the first drug to correct the basic defect |
De-escalating older therapies
| Trial | Year | Therapy | Effect | Finding |
|---|---|---|---|---|
| SIMPLIFY | 2023 | Hypertonic saline and dornase alfa withdrawal | Patients on triple modulator therapy could stop hypertonic saline or dornase alfa without losing lung function |
Key references
Guidelines, standards and reviews for this topic.
- Guidelines
- 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 Jan;71(1):88-90. PMID 26678435
- Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med 2009 Nov 1;180(9):802-8. PMID 19729669
- Respiratory complications of CF
- Mingora CM, Flume PA. Pulmonary Complications in Cystic Fibrosis: Past, Present, and Future: Adult Cystic Fibrosis Series. Chest 2021 Oct;160(4):1232-1240. PMID 34147501
- Reviews
- Grasemann H, Ratjen F. Cystic Fibrosis. N Engl J Med 2023 Nov 2;389(18):1693-1707. PMID 37913507
Studies not yet summarised
On the reading list for this topic and awaiting a full record. Listed here so nothing is hidden.
- Therapeutics - CFTR Modulators
- Barry PJ, Mall MA, Álvarez A, et al. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med 2021 Aug 26;385(9):815-825. PMID 34437784
- Treatment of exacerbations
- Goss CH, Heltshe SL, West NE, et al. A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment. Am J Respir Crit Care Med 2021 Dec 1;204(11):1295-1305. PMID 34469706