Summary

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• This summary is based on the review of seven systematic review(s)/meta-analysis(es). ^[1-7]
• Dual Therapy: In patients with cystic fibrosis, dual therapies (lumacaftor-ivacaftor and tezacaftor-ivacaftor) showed moderate-certainty improvements in quality of life (QoL) in respiratory domains and significant improvements in lung function (FEV(1) % predicted) compared to placebo. Additionally, dual therapies were associated with reduced rates of pulmonary exacerbations (moderate-certainty evidence).
• Triple Therapy: Triple therapy (elexacaftor-tezacaftor-ivacaftor) provided moderate-certainty evidence of improved QoL scores and significant increases in FEV(1) % predicted, both in relative and absolute terms. It also led to fewer pulmonary exacerbations at four and 24 weeks compared to placebo, with notably higher improvements than dual therapies for patients with the F508del/F508del genotype.
• Comparative Effectiveness: When comparing dual and triple therapies, triple therapy (elexacaftor-tezacaftor-ivacaftor) demonstrated greater enhancements in QoL and FEV(1) % predicted and showed a more favorable safety profile relative to dual therapies, particularly lumacaftor-ivacaftor.
• Dual Therapy Safety: In dual therapy, lumacaftor-ivacaftor was associated with high-certainty evidence of transient breathlessness and increased blood pressure in long-term data, which were not observed with tezacaftor-ivacaftor, giving it a more favorable safety profile.
• Triple Therapy Safety: Triple therapy (elexacaftor-tezacaftor-ivacaftor) demonstrated minimal differences in adverse events compared to control, showing a more favorable safety profile than dual therapies, particularly lumacaftor-ivacaftor.
• Real-World Observations: Real-world data indicated higher rates of respiratory-related adverse events and treatment discontinuation with lumacaftor-ivacaftor. Additionally, a potential signal for mental health and neurocognitive adverse events was identified across all four CFTR (cystic fibrosis transmembrane conductance regulator) modulators (ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, elexacaftor-tezacaftor-ivacaftor).
• There is no population types or subgroups information available in the reviewed studies.