The Cystic Fibrosis Foundation published recommendations for the use of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators in patients with CF in the Annals of the American Thoracic Society.
The Cystic Fibrosis Foundation selected cochairs to develop guidelines along with a multidisciplinary committee of CF caregivers and patient representatives. They also recruited a methodologist, an epidemiologist, a medical librarian, and a biostatistician to assist with the literature search, evidence grading, and creation of recommendations.
Using the Patient, Intervention, Comparison, and Outcome format, the committee developed clinical questions. They conducted a systematic review to find relevant publications and then evaluated the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Based on the evidence gathered and analyzed, the committee made recommendations regarding the use of the CFTR modulators.
CFTR modulators are small molecules that can partially restore function in mutated CFTR. Ivacaftor (IVA) and IVA combined with lumacaftor (IVA/LUM) have been approved by the US Food and Drug Administration for use in patients with CF. They have the potential to revolutionize CF care and may prevent disease progression by correcting the fundamental defect of CF.
The committee developed the following recommendations regarding IVA and IVA/LUM:
- For adults and children ≥6 years with CF as a result of gating mutations other than G551D or R117H, there is a conditional recommendation for IVA. For patients with the R117H mutation, there is a conditional recommendation for IVA treatment in adults ≥18 years and children aged 6 to 17 years with a forced expiratory volume in 1 second (FEV1) <90% predicted.
- For patients with R117H mutation, there is a conditional recommendation against treatment with IVA in children aged 12 to 17 years with FEV1 >90% and children ≤6 years.
- In individuals with 2 copies of F508del, there is a strong recommendation for treatment with IVA/LUM in adults and children ≥12 years with FEV1 <90% predicted, and there is a conditional recommendation for treatment with IVA/LUM in adults and children ≥12 years with FEV1 >90% and children aged 6 to 11 years.
Ren CL, Morgan RL, Oermann C, et al. Cystic Fibrosis Foundation pulmonary guidelines: use of CFTR modulator therapy in patients with cystic fibrosis [published online January 17, 2018]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201707-539OT