IntroductionCystic fibrosis transmembrane conductance regulator modulator therapies (CFTR‐MT) have altered management, reducing exacerbations and slowing pulmonary function decline. Nevertheless, it is still uncertain if the benefits of CFTR‐MTs last when they are stopped. This study aimed to assess pulmonary function changes, and exacerbation rates during and after CFTR‐MT use in adult cystic fibrosis patients.MethodsBetween 2018 and 2022, we conducted a study involving adult CF patients who initially used CFTR‐MTs but later discontinued them due to reimbursement issues. The study was divided into three phases: predrug (T1), in‐drug (T2), and postdrug (T3). We recorded pulmonary function tests, laboratory and culture results, and the number of exacerbations.ResultsThe study involved 33 patients, with 28 (84.8%) receiving Elexacaftor/Tezacaftor/Ivacaftor and 5 (15.2%) receiving Ivacaftor. The median treatment and interruption durations were 3.1 (IQR = 2.9–5.7), and 2.5 (IQR = 1.5–4.0) months, respectively. The mean FEV1% was 54.3% (± 26.6), 70.4% (± 27.4), and 60.2% (± 26.5) during T1, T2, and T3, respectively (p < 0.001). The mean FVC% was 65.5% (± 23.9) in T1, increased to 81.5% (± 24.5) in T2, and decreased to 71.6% (± 25.9) in T3 (p < 0.001). The number of Psedomonas aeruginosa, and Aspergillus positive sputum cultures decreased significantly with drug use (T1: 72.7%, 39.4%; T2: 48.5%, 9.1%; T3: 45.5%, 18.2%; p = 0.014, p = 0.004, respectively). The median number of hospitalizations was 1.0 (0–5.0) in T1, 0 (0–0) in T2, and 0 (0–1.0) in T3.ConclusionThis study revealed that CFTR‐MTs are effective even in the short term for adult CF patients, but their beneficial effects quickly diminish after discontinuation. Real‐life data obtained as a result of discontinuation of drugs due to reimbursement problems has highlighted the significance of regular and uninterrupted use of modulators.