Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) for patients with cystic fibrosis (CF) is not well tolerated by lung transplant recipients and offers only modest benefits, according to a study published in Pharmacotherapy. The researchers also found a 50% decline in tacrolimus dose requirements in the study group.

The research team reviewed data on 13 lung transplant recipients with CF from a single center between November 2019 and July 2021. The primary endpoint was documented adverse events related to ELX/TEZ/IVA and withdrawal of the therapy due to adverse events. Secondary endpoints were patient-reported efficacy, pulmonary function, and body mass index (BMI).

The results found ELX/TEZ/IVA to be poorly tolerated by lung transplant recipients with CF, with negative effects on pulmonary function and on mental health. There were modest perceived extrapulmonary benefits and a decline in BMI, and, in contrast with other studies, a reduction in tacrolimus dose requirements was observed.

Also in contrast with ELX/TEZ/IVA approval studies that showed good tolerance to the treatment, in this study, 38.4% of the patients discontinued the therapy due to pulmonary and nonpulmonary concerns.

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The research team noted that mood disturbances were a particularly common adverse event associated with ELX/TEZ/IVA in this patient group, possibly due to drug-drug interactions, CF transmembrane conductance regulator modification in the brain, or perhaps simply due to screening of a population that is known to have a greater prevalence of mood disorders.

Given that the results conflict with those of other published experiences, the authors recommend close monitoring of lung transplant recipients with CF on ELX/TEZ/IVA therapy and further studies to better optimize the use and dosage of this therapy with these patients.

Reference

Doligalski CT, McKinzie CJ, Yang A, et al. Poor tolerability of cystic fibrosis transmembrane conductance regulator modulator therapy in lung transplant recipients. Pharmacotherapy. Published online June 11, 2022. doi:10.1002/phar.2710