Elexacaftor-tezacaftor-ivacaftor use after solid organ transplant

Area of Science:

• Pharmacology
• Transplantation Medicine
• Pulmonology

Background:

• Cystic fibrosis treatment has advanced with elexacaftor-tezacaftor-ivacaftor (ETI).
• ETI targets the underlying protein defect in cystic fibrosis, improving both pulmonary and nonpulmonary symptoms.
• Transplant recipients were excluded from initial ETI trials, raising questions about its safety and efficacy in this population.

Purpose of the Study:

• To review the existing literature on the use of ETI in solid organ transplant recipients.
• To assess the safety and efficacy of ETI, focusing on potential drug interactions with immunosuppressants.
• To evaluate the benefits and risks of ETI in both lung and nonlung transplant recipients with cystic fibrosis.

Main Methods:

• Review of recent publications and real-world evidence on ETI use post-transplantation.
• Analysis of reported drug interactions between ETI and immunosuppression medications (e.g., tacrolimus).
• Assessment of adverse events and clinical outcomes in lung and nonlung transplant recipients.

Main Results:

• ETI demonstrates pulmonary benefits in nonlung transplant recipients, though adverse events can impact the transplanted organ.
• Lung transplant recipients may experience higher discontinuation rates due to side effects and lack of direct pulmonary benefit.
• Drug interactions with ETI and immunosuppressants are manageable, with mild to moderate increases in tacrolimus levels observed.

Conclusions:

• Limited data necessitate further research on ETI use in solid organ transplant recipients.
• Case-by-case evaluation is recommended for lung transplant recipients, particularly when nonpulmonary manifestations are present.
• For nonlung solid organ transplant recipients, the benefits of ETI for cystic fibrosis likely outweigh the risks.