(120) Sleep disturbances after initiation of elexacaftor/tezacaftor/ivacaftor

Background: The CFTR-modulator elexacaftor/tezacaftor/ivacaftor was approved by the U.S. Food and Drug Administration (FDA) in October 2019 for patients with cystic fibrosis (CF) and at least one F508del mutation [1]. Phase 3 trials indicated that it is generally well tolerated and patients participating in the trials did not report any sleep disturbances [2]. However, sleep disturbances related to CF can occur and poor sleep can impact health outcomes [3]. Additionally, while no sleep disturbances were reported in trials, one case study reported sleep paralysis with hypnopompic hallucinations, depression, and anxiety after initiation of elexacaftor/tezacaftor/ivacaftor. Therefore, it is important to assess for sleep disturbances after initiation of this modulator as a routine part of CF care. The goal of this study was to examine self-reported sleep disturbances in patients with CF after initiation of elexacaftor/tezacaftor/ivacaftor.

Methods: A retrospective chart review was conducted of adult patients with CF (n=127) receiving care at an Adult CF Clinic in an academic health center in the Southeastern United States from January 2015 to February 2022. Data collected included demographic data, FEV1 percent predicted (ppFEV1; predicted for age, gender, and height) at each visit, consistency and timeline of elexacaftor/tezacaftor/ivacaftor use, and self-reported sleep disturbances.

Results: One hundred and twenty seven patients were screened for study eligibility and 100 patients were included. Around a quarter (23%) of patients reported new onset sleep issues and 30% reported pre-existing sleep issues that continued after initiation of elexacaftor/tezacaftor/ivacaftor. Two patients discontinued the modulator after reporting significant insomnia, anxiety, and depression.

Conclusions: New onset or ongoing sleep disturbances after initiation of elexacaftor/tezacaftor/ivacaftor were reported by over half of the patients and contributed to two patients discontinuing the modulator. It is important to screen for and treat sleep disturbances as a routine part of CF care.

Acknowledgements:

References: [1] Hoy SM. Elexacaftor/ivacaftor/tezacaftor: first approval. Drugs. 2019;79(18):2001-2007. https://doi: 10.1007/s40265-019-01233-7.
[2] Heijerman HGM, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940-1948. https://doi: 10.1016/S0140-6736(19)32597-8.