CFTR modulator monotherapy for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del)
Abstract
RATIONALE: Cystic fibrosis (CF) is a common, life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR gene variant, F508del, is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF) in some populations). The F508del variant lacks meaningful CFTR function: the faulty protein is degraded before reaching the cell membrane, where it would normally transport salt across the epithelial membrane. Corrective therapy with CFTR modulators could benefit many pwCF. This review evaluates treatment with single modulators (monotherapy).
OBJECTIVES: To evaluate the clinically important benefits and harms of CFTR modulator monotherapy in people of any age with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
SEARCH METHODS: We last searched the Cochrane CF Trials Register and online trials registries on 27 June 2025. We also checked the reference lists of relevant articles for additional studies.
ELIGIBILITY CRITERIA: We included parallel-group randomised controlled trials (RCTs) comparing any single CFTR modulator to placebo or any other single CFTR modulator in pwCF of any age or disease severity with class II variants.
OUTCOMES: Our critical outcomes were survival, quality of life (total score and respiratory domain), and forced expiratory volume in one second (FEV1 % predicted; relative and absolute change from baseline). Our important outcomes included…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 424 participants or records.
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