WS14.1 Ivacaftor improves exercise capacity in patients with G551D CF gene mutations

Abstract

Introduction G551D is a CFTR mutation that results in impaired chloride channel function in Cystic Fibrosis (CF). Ivacaftor, a CFTR potentiating agent improves lung function and sweat chloride but its effect on exercise is unproven. Objectives To evaluate exercise capacity in response to correction of the chloride channelopathy with ivacaftor. Methods In a placebo-controlled crossover study of ivacaftor over 4 months with a 3 month open label extension we performed cardiopulmonary exercise tests (CPET) at six time points. 20 patients were included in the study. The primary outcome was VO2max as a percentage of baseline at the end of the crossover study (END X) and 3 month open label extension (OLE). A training program was not included in the study. Results There was a stepwise increase in maximal exercise capacity based on VO2max in the treated group above baseline at END X and 3 month OLE treatment periods. FEV1 and sweat chloride were also improved as expected. EndpointEnd X, mean (95% CI)OLE, mean (95% CI)%Δ absolute exercise time8.0 (1.4–14.6) * 12.1 (5.8–18.4) *** %Δ VO2max, ml/kg/min6.7 (2.7–10.8) ** 12.6 (6.3–18.9) *** %Δ VO2 ml/min7.8 (3.7–12.0) *** 15.6 (9.7–21.4) *** %Δ Watts5.0 (1.4–8.6) ** 10.9 (5.6–16.3) *** *p Conclusion Treatment of G551D patients with ivacaftor has a positive effect on exercise capacity which is independent of training. Improved VO2max has not been previously examined in clinical trials with ivacaftor and may have prognostic implications for patients with the G551D mutation. Supported by a grant from Vertex Inc.