Objective: Ivacaftor, a CFTR potentiator, is indicated in patients with CF 6 years and older carrying a G551D mutation. It has been available in France since April 2012. Our aim was to review the efficacy and safety data in French patients treated with ivacaftor in real life setting. Methods: An independent retrospective survey was completed by email by physicians from French CF centers who had patients treated with ivacaftor. Collected information included birth date, gender, date of first treatment with ivacaftor, FEV1 and weight at treatment initiation, after one, 3, 6, 9 and 12 months of treatment, sweat chloride before and after initiation of treatment, adverse events and any treatment interruption. Results: Survey included 57 patients from 26 CF centers (34 males, 23 females), with a mean age of 21.1 years (6.1 to 51.8) over the April 2012 to May 2013 period. Eighteen patients were children aged 6-12 years. Baseline mean FEV1 (± SD) was 73.8 (± 25.0) % predicted (% pred). There was an increase from baseline of 9.8 (± 9.7), 9.0 (± 10.0), 6.2 (± 19.8), 8.1 (± 14.8) and 12.7 (± 12.6) percentage points of predicted FEV1, respectively at Months 1 (n=49), 3 (n=53), 6 (n=42), 9 (n=28) and 12 (n=15). In the 9 patients whose FEV1 was <40% pred at initiation of treatment, there was an increase from baseline of 7.4 (± 4.2) percentage points of predicted FEV1 at Month 6. In children aged 6-12, mean FEV1 before treatment was 87.8 (± 13.3) % pred and the increase in FEV1 was 9.2 (± 8.9) % at Month 1 (n=15), 5.3 (± 9.9) % at Month 3 (n=14), 2.2 (± 11.8) % at Month 6 (n=12) and 10.3 (± 13.4) % at Month 12 (n=6). Weight increased from baseline of 1.0 (± 1.4), 2.0 (± 2.2), 2.3 (± 5.3), 3.3 (± 2.9) and 3.8 (± 2.0) kg, respectively at Months 1, 3, 6, 9 and 12. Mean sweat chloride value was 103 (± 28) mmol/L before (n=41) and 40 (± 42) mmol/L after initiation of treatment with ivacaftor (n=30). Adverse events considered as potentially drug related included headache (n=5), nausea (n=2), abdominal pain (n=2), asthenia (n=2), dizziness (n=2), skin rash (n=1), breast hypertrophy (n=1), asthma requiring corticosteroid treatment (n=2), tachyarrhythmia with atrial fibrillation (n=1) and hepatitis (n=2). Two patients interrupted ivacaftor from day 7 of treatment to day 35, one for rash, one for digestive symptoms; events did not recur when ivacaftor treatment was resumed. Ivacaftor was discontinued after 9 months treatment in a third patient at time of pulmonary exacerbation with asthma, because of severe hepatitis. Conclusion: Preliminary results with ivacaftor in French CF patients in real world setting showed a similar benefit (increase in FEV1 and weight) and safety profile than that seen in clinical trials.
Hubert, D., David, V., Rault, G., Dominique, S., Mély, L., & Munck, A. (2013). 57 Ivacaftor in French patients with cystic fibrosis and a G551D mutation in the real world setting. Journal of Cystic Fibrosis, 12, S63. https://doi.org/10.1016/s1569-1993(13)60199-x