(187) Use of Sweat Chloride Testing to Assess Adherence to and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor Treatment in a Pediatric Cystic Fibrosis Clinic
CF Center Director University of Vermont Children's Hospital Burlington, Vermont, United States
Background: The use of elexacaftor/tezacaftor/ivacaftor (ELEXA) for patients > 6 years old with cystic fibrosis (CF) and qualifying mutations has had a tremendous positive impact on lung function and quality of life for many people with CF. Clinical trial data demonstrated substantial increases of forced expiratory volume in 1 second (FEV1), large decreases of sweat chloride (SCl) values, and decreased pulmonary exacerbation rates. Our clinic made the decision to use SCl testing to assess real world physiologic responses to ELEXA at the individual patient level and discover whether adherence factors affected the values.
Methods: Our pediatric CF program performed SCl testing on children with CF who had been using ELEXA for at least 1 month. Pre-ELEXA and best post-ELEXA lung function (FEV1) were recorded. Pre-ELEXA spirometry was performed within the 1 month prior to starting treatment, and post-ELEXA spirometry within 1 month following initiation. Refill history for ELEXA was reconciled by the CF pharmacist with the distributing pharmacy to assess adherence in addition to interviews with patients and parents. Twenty-two patients (age range 6-20 years) underwent SCl testing. Baseline measurements included mean FEV1 percent predicted of 96.9 (range 63-136) and mean SCl of 103.7 mmol/L (range 37-122).
Results: The mean increase of percent predicted FEV1 following ELEXA treatment was 18.4 points (range 7 to 40) for the studied patients. The mean post-FEV1 was 115.3 percent predicted (range 86-156). The mean decrease of SCl was 61 mmol/L (range 24-89) with mean SCl levels of 42.7 mmol/L (range 13-74). With regard to medication adherence, some interesting results were found. Two patients who underwent SCl testing had missed their last 5 doses of ELEXA due to delivery issues and had modest decreases of SCl. After resuming regular dosing, both patients had a further decrease of SCl by 19 and 20 mmol/L, respectively. Another patient with a robust FEV1 increase (27 percentage points) post-ELEXA then experienced a decline of lung function back to pre-ELEXA levels despite reported good adherence. A SCl was performed and was unchanged from pre-ELEXA levels (96, 97 mmol/L). Further questioning revealed that the pediatric patient had not been taking any doses of ELEXA for several weeks as he was feeling well and was unsupervised. Direct parental and school supervision of ELEXA administration was instituted with subsequent increase of FEV1 and decrease of SCl to 40 and 42 mmol/L, a decrease of 54 mmol/L.
Conclusions: SCl testing is a useful tool to determine an individual’s response to ELEXA treatment. In a real world setting our results indicate an even greater effect on lung function and sweat chloride compared to those previously reported. Based on our limited experience, SCl testing may be useful to identify potential adherence issues and can be used to emphasize the importance of consistent ELEXA use to achieve the most favorable outcomes.
References: Middleton PG, Mall MA, Drevinek P, Lands LC, et al. Elexacaftor-Tezacaftor-Ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019; 381:1809-19. doi:10.1056/nejmoa1908639.
