Effect of Triple Combination CFTR Modulator Therapy on Sleep in Adult Patients with Cystic Fibrosis

Abstract

<b><i>Background:</i></b> Sleep-disordered breathing (SDB) and disturbed sleep are common, often underrecognized, comorbidities in people with cystic fibrosis (pwCF). <b><i>Objectives:</i></b> We studied the effect of CFTR triple combination therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on sleep in pwCF. <b><i>Method:</i></b> This was a prospective, observational sleep study in clinically stable adult pwCF. All participants underwent overnight polysomnography (PSG), before (T0) and after (T1) initiation of CFTR modulator therapy with ELX/TEZ/IVA. In addition, pulmonary function tests, calculation of BMI, and sweat chloride testing were performed. <b><i>Results:</i></b> Twenty-nine pwCF (mean age 32 ± 8 years; 15 female) participated in the study. Mean time between T0 and T1 was 194 ± 21 days. Total sleep time (TST) was 298 ± 40 min, with decreased sleep efficiency (SE) (76 ± 109) and increased sleep latency (SL) (73 ± 38 min). Sleep stages for NREM (N1–3) and REM sleep were within the normal range. Nocturnal respiratory events mainly occur during REM sleep (T0: AHI REM 8.3 ± 9.0/h; ODI REM 9.4 ± 10.6/h), whereas the overall AHI was normal (3.6 ± 3.7/h). After initiation of ELX/TEZ/IVA, we saw significant improvements in ppFEV1 (<i>p</i> &#x3c; 0.001) and BMI (<i>p</i> &#x3c; 0.001) and a reduction in sweat chloride levels (<i>p</i> &#x3c; 0.001). In parallel, there was a reduction in AHI (<i>p</i> = 0.003), ODI (<i>p</i> = 0.001), and nocturnal respiratory rate (<i>p</i> &#x3c; 0.001), both in total, REM and NREM sleep. Neither TST, SL, SE, nor sleep architecture was influenced (all <i>p</i> &#x3e; 0.05). <b><i>Conclusions:</i></b> Initiation of ELX/TEZ/IVA resulted in significant improvements in SDB in adult pwCF.