Efficacy response in CF patients treated with ivacaftor: Post-hoc analysis

Abstract

Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the group treated with ivacaftor had improved clinical outcomes. To better understand the effect of ivacaftor therapy across the distribution of individual FEV(1) responses, data from Phase 3 studies (STRIVE/ENVISION) were re-examined. In this post-hoc analysis of patients (n = 209) who received 48 weeks of ivacaftor or placebo, patients were assigned to tertiles according to FEV(1) response. These groups were then used to evaluate response (FEV(1), sweat chloride, weight, CFQ-R, and pulmonary exacerbation). The number needed to treat (NNT) was calculated for specific thresholds for each outcome. Across all tertiles, numerical improvements in FEV(1), sweat chloride, CFQ-R and the frequency of pulmonary exacerbations were observed in ivacaftor-treated patients: the treatment difference versus placebo was statistically significant for all outcomes in the upper tertile and for some outcomes in the lower and middle tertiles. The NNT for a ≥ 5% improvement in %predicted FEV(1) was 1.90, for a ≥ 5% body weight increase was 5.74, and to prevent a pulmonary exacerbation was 3.85. This analysis suggests that the majority of patients with clinical characteristics similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor therapy.

Use of ivacaftor in late diagnosed cystic fibrosis monozygotic twins heterozygous for F508del and R117H-7T – a case report

“…The use of ivacaftor can result in a decrease of sweat chloride, an increase of lung function and reduction of pulmonary exacerbations in many patients [32, 33]. However, the clinical response to ivacaftor is very heterogeneous and shows great variability.…”

Pediatric Pulmonologyyear in review 2015: Part 4

“…Patients with G551D on ivacaftor showed sustained FEV1% increases of 5% through 48 weeks. 78 In individuals with an FEV1% predicted response of <5%, there was still improvement in lung function outcomes and weight and a trend toward improvement in the respiratory domain of CFQ-R and pulmonary exacerbations, establishing that FEV1% predicted should not be used as be the sole indicator of benefit. Follow-up of patients with the G551D mutation on ivacaftor for up to 3 years found a slower rate of decline in FEV1 by almost half compared to individuals with F508del, as well as improved BMI and weight for age.…”

“…Ivacaftor has been available for several years to patients with specific mutations. Patients with G551D on ivacaftor showed sustained FEV1% increases of 5% through 48 weeks . In individuals with an FEV1% predicted response of <5%, there was still improvement in lung function outcomes and weight and a trend toward improvement in the respiratory domain of CFQ‐R and pulmonary exacerbations, establishing that FEV1% predicted should not be used as be the sole indicator of benefit.…”

New and Emerging Treatments for Cystic Fibrosis

“…In the field of CFTR modulation, the deficiencies of sweat chloride in predicting clinical response clearly establish the need for better markers of CFTR function [88][89][90]. The development of robust markers could aid in providing new therapies for all, but particularly 'non-responders' to existing therapy, and enable researchers to better examine the heterogeneity of clinical response witnessed in clinical trials [91].…”