Drucy Borowitz1, Barry Lubarsky2, Michael Wilschanski3, Anne Munck4, Daniel Gelfond5, Frank Bodewes6, Sarah Jane Schwarzenberg7. 1. Department of Pediatrics, University at Buffalo, State University of New York, Women and Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, NY, 14222, USA. dborowitz@upa.chob.edu. 2. Department of Medical Affairs, Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, 02210, USA. barry_lubarsky@vrtx.com. 3. Department of Pediatrics, Hadassah University Hospital, Kiryat Hadassah, PO Box 12000, 91120, Jerusalem, Israel. michaelwil@hadassah.org.il. 4. Assistance publique-Hôpitaux de Paris, Hôpital Robert Debré, Paediatric Gastroenterology and Respiratory Department, CF Center, 48 Sérurier Boulevard, 75019, Paris, France. anne.munck@rdb.aphp.fr. 5. Department of Pediatrics, Gastroenterology/Nutrition (SMD), University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA. dgelfond@upa.chob.edu. 6. Department of Pediatrics, Beatrix Children's Hospital, PO Box 30001, 9700 RB, Groningen, Groningen, The Netherlands. f.a.j.a.bodewes@umcg.nl. 7. Division of Pediatric Gastroenterology, University of Minnesota, 6th Floor East Building 8952C 2450 Riverside Ave, Minneapolis, MN, 55454, USA. schwa005@umn.edu.
Abstract
BACKGROUND: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gating mutation G551D prevents sufficient ion transport due to reduced channel-open probability. Ivacaftor, an oral CFTR potentiator, increases the channel-open probability. AIM: To further analyze improvements in weight and body mass index (BMI) in two studies of ivacaftor in patients aged ≥6 years with CF and the G551D mutation. METHODS: Patients were randomized 1:1 to ivacaftor 150 mg or placebo every 12 h for 48 weeks. Primary end point (lung function) was reported previously. Other outcomes included weight and height measurements and CF Questionnaire-Revised (CFQ-R). RESULTS: Studies included 213 patients (aged ≤ 20 years, n = 105; aged > 20 years, n = 108). In patients ≤20 years, adjusted mean change from baseline to week 48 in body weight was 4.9 versus 2.2 kg (ivacaftor vs. placebo, p = 0.0008). At week 48, change from baseline in mean weight-for-age z-score was 0.29 versus -0.06 (p < 0.0001); change in mean BMI-for-age z-score was 0.26 versus -0.13 (p < 0.0001). In patients >20 years, adjusted mean change from baseline to week 48 in body weight was 2.7 versus -0.2 kg (p = 0.0003). MeanBMI change at week 48 was 0.9 versus -0.1 kg/m(2) (p = 0.0003). There was no linear correlation evident between changes in body weight and improvements in lung function or sweat chloride. Significant CFQ-R improvements were seen in perception of eating, body image, and sense of ability to gain weight. CONCLUSIONS:Nutritional status improved following treatment with ivacaftor for 48 weeks.
RCT Entities:
BACKGROUND: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gating mutation G551D prevents sufficient ion transport due to reduced channel-open probability. Ivacaftor, an oral CFTR potentiator, increases the channel-open probability. AIM: To further analyze improvements in weight and body mass index (BMI) in two studies of ivacaftor in patients aged ≥6 years with CF and the G551D mutation. METHODS:Patients were randomized 1:1 to ivacaftor 150 mg or placebo every 12 h for 48 weeks. Primary end point (lung function) was reported previously. Other outcomes included weight and height measurements and CF Questionnaire-Revised (CFQ-R). RESULTS: Studies included 213 patients (aged ≤ 20 years, n = 105; aged > 20 years, n = 108). In patients ≤20 years, adjusted mean change from baseline to week 48 in body weight was 4.9 versus 2.2 kg (ivacaftor vs. placebo, p = 0.0008). At week 48, change from baseline in mean weight-for-age z-score was 0.29 versus -0.06 (p < 0.0001); change in mean BMI-for-age z-score was 0.26 versus -0.13 (p < 0.0001). In patients >20 years, adjusted mean change from baseline to week 48 in body weight was 2.7 versus -0.2 kg (p = 0.0003). Mean BMI change at week 48 was 0.9 versus -0.1 kg/m(2) (p = 0.0003). There was no linear correlation evident between changes in body weight and improvements in lung function or sweat chloride. Significant CFQ-R improvements were seen in perception of eating, body image, and sense of ability to gain weight. CONCLUSIONS: Nutritional status improved following treatment with ivacaftor for 48 weeks.
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