Effectivenesss of ivacaftor in severe cystic fibrosis patients and non-G551D gating mutations

Background: Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined. Methods: Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV1] < 40%, or on lung transplant waiting list, or with a fast worsening trend of lung function). Data were collected for 1 year before and 1 year after ivacaftor commencement. Results: Thirteen patients received ivacaftor for a median of 320 days. Mean (SD) ppFEV1 increased from 35.1% (14.3%) before treatment to 46.6% (18.8%) after 12 months of treatment (absolute increase 11.5%, relative increase 32.8%). Mean distance of the 6-minute walking test improved significantly, from 535.1 m before to 611.6 m after 12 months of treatment (P =.002). The number of pulmonary exacerbations decreased significantly, from 57 during the year before ivacaftor to 28 in the year following ivacaftor (P =.0048). Five of the 13 patients (38.5%) had no exacerbations during the 12 months after starting ivacaftor. Median weight increased significantly, from 52.7 kg to 55.6 kg (P =.0031). Mean (SD) sweat chloride concentration decreased significantly, from 99.5 (22.8) mmol/L to 39.3 (15.8) mmol/L (P <.0001). No safety concerns were registered. Conclusions: Ivacaftor was safe and effective in patients with CF with severe lung disease and non-G551D gating mutations.