Can supportive therapies be discontinued in patients with cystic fibrosis treated with Elexacaftor (VX-661)/Tezacaftor (VX-661)/Ivacaftor (Kalydeco)?

Discontinuation of Supportive Therapies in People with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor

Supportive therapies can be safely discontinued in patients with cystic fibrosis who demonstrate clinical improvement and stability after initiating elexacaftor/tezacaftor/ivacaftor (ETI) therapy, using a structured de-escalation algorithm. 1

Evidence for Discontinuation of Supportive Therapies

• A 2024 retrospective study demonstrated that de-escalating supportive therapies in patients on ETI was non-inferior to maintaining all supportive therapies, with continued improvement in lung function over 12 months 1
• Patients on ETI showed significant clinical improvements that persisted despite discontinuation of supportive therapies, with mean ppFEV1 improving from 67% at baseline to 87% at 12 months 1
• The FDA label for elexacaftor/tezacaftor/ivacaftor (TRIKAFTA) confirms substantial improvements in lung function, with increases in ppFEV1 of 10.0 percentage points compared to previous CFTR modulators 2

Recommended De-escalation Algorithm

When considering discontinuation of supportive therapies in patients on ETI:

1. Initial Assessment Period

   • Ensure patient has been on ETI for at least 1 month with documented clinical improvement 1
   • Verify stability in lung function (ppFEV1) and absence of pulmonary exacerbations 1

2. Sequential De-escalation Approach

   • Discontinue therapies gradually at quarterly intervals rather than all at once 1
   • Monitor lung function, symptoms, and quality of life after each medication discontinuation 1

3. Priority for Discontinuation

   • First tier: Consider discontinuing inhaled medications with insufficient evidence of benefit, such as inhaled anticholinergics and beta-adrenergic receptor agonists 3
   • Second tier: Consider discontinuing medications with low certainty of benefit, such as leukotriene modifiers, N-acetylcysteine, and glutathione 3
   • Third tier: Consider discontinuing oral antistaphylococcal antibiotics if appropriate 3

Cautions and Monitoring

• Continue close monitoring of lung function, symptoms, and quality of life after discontinuation of any supportive therapy 1
• Be prepared to reinstate therapies if clinical deterioration occurs 1
• Some patients with residual symptoms may benefit from continuing certain supportive therapies 3

Special Considerations

• Patients with advanced lung disease (ppFEV1 <40%) who show improvement on ETI may still benefit from a more conservative de-escalation approach 4, 5
• The long-term benefits of ETI include substantial improvements in survival (projected median survival of 71.6 years) and reduced disease severity 6
• ETI has been shown to significantly reduce pulmonary exacerbations from 3.9 to 0.9 per year in patients with advanced disease, which may further support the discontinuation of some preventive therapies 4

Benefits of De-escalation

• Decreased medication burden for patients 1
• Reduced treatment costs 1
• Improved quality of life through simplified treatment regimens 1
• Maintained or improved lung function despite fewer medications 1

This approach to discontinuing supportive therapies in CF patients on ETI should be implemented with careful monitoring and a structured plan, recognizing that the substantial efficacy of ETI may reduce or eliminate the need for many traditional supportive therapies while maintaining or improving clinical outcomes.