Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data

Sawicki, Gregory S.; McKone, Edward F.; Pasta, David J.; Millar, Stefanie J.; Wagener, Jeffrey S.; Johnson, Charles A.; Konstan, Michael W.

doi:10.1164/rccm.201503-0578oc

Cited by 215 publications

(142 citation statements)

References 28 publications

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“…When the results of the STRIVE and PERSIST studies are combined, current clinical evidence has documented the efficiency of ivacaftor for up to three years of treatment 19 . Our study showed consistent improvement and stabilization of lung function in a small group of CF adults treated with ivacaftor for up to six years.…”

Section: Discussionmentioning

confidence: 99%

Ivacaftor in cystic fibrosis adults: Czech experience with six years of follow-up

Fila¹,

Bartakova²,

Grandcourtova³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. Ivacaftor is a revolutionary treatment option for cystic fibrosis (CF) patients with G551D and other gating mutations. The aim of this study was to evaluate the clinical status of patients on ivacaftor who were followed for up to 6 years together with an evaluation of ivacaftor therapy in one patient with an initial FEV 1 less than 40% of predicted value. Methods. Data on development of clinical status and sinopulmonary-related therapies were obtained from patient health records during ivacaftor treatment lasting for up to six years and were compared with an equivalent period before ivacaftor administration. Results. Five CF adults with a median age 28.6 years (range 21.4−35.6 years) with median FEV 1 45% pred. (range 16−85% pred.) were included in the study. Four subjects were also participants in the STRIVE and PERSIST studies. Altogether, twenty-four patient-years of ivacaftor treatment were analyzed. The median FEV 1 decline per year decreased from -4.5 to -0.9% pred. (P = 0.043). Reduction in number of days on antibiotic treatment and hospital stays was 21% (P < 0.001) and 75% (P = 0.003), respectively. Improvement and stabilization of lung function was observed for up to six years of treatment. In a patient with severe airway obstruction, an increase in the FEV 1 value (30.4% from baseline) was documented during the first twelve months of treatment. Conclusion. Ivacaftor therapy resulted in improved and stabilized lung function in up to six years of treatment with a reduction in number of days on antibiotic treatment and hospital stays. Its efficiency was also displayed in a patient with severe airway obstruction.

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Section: Discussionmentioning

confidence: 99%

Ivacaftor in cystic fibrosis adults: Czech experience with six years of follow-up

Fila¹,

Bartakova²,

Grandcourtova³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…14,15 Two observational studies have confirmed ivacaftor’s real-world effectiveness: A patient registry study found that lung function declined more slowly among patients using ivacaftor, compared to a control group receiving standard care; and an analysis of private insurance claims found lower rates of hospitalization. 16,17 …”

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confidence: 99%

Precision Medicine In Action: The Impact Of Ivacaftor On Cystic Fibrosis–Related Hospitalizations

et al. 2018

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Cystic fibrosis is a life-threatening genetic disease that causes severe damage to the lungs. Ivacaftor, the first drug that targeted the underlying defect of the disease caused by specific mutations, is a sterling example of the potential of precision medicine. Clinical trial and registry studies showed that ivacaftor improved outcomes and reduced hospitalizations. Our study used US administrative claims data to assess the real-world effectiveness of ivacaftor. Comparing twelve-month rates before and after starting the use of ivacaftor among people who initiated therapy during 2012–2015, we found that overall and cystic fibrosis–related inpatient admissions fell by 55 percent and 81 percent, respectively. There was a comparable reduction in inpatient spending. Ivacaftor appears to be effective for multiple mutations that cause the disease, as suggested by the fact that during the study period, ivacaftor’s use was extended to nine additional mutations in 2014. Examination of evidence from clinical trial, clinical care, and administrative data sources is important for understanding the real-world effectiveness of precision medicines such as ivacaftor.

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“…96 An open label extension study examining ivacaftor in people with at least one G551D mutation enrolled in the two RCTs 20 91 has shown a durable treatment response up to 144 weeks, with no new safety concerns. 97 An observational follow-up study of these patients using CF Foundation registry data up to three years showed that ivacaftor can reduce the rate of FEV 1 decline by about 50% relative CFTR read-through agents Open label pilot studies have shown that both the topical and systemic administration of the aminoglycoside gentamicin can augment chloride transport (based on measurement of nasal potential difference; NPD) in people with cystic fibrosis and at least one nonsense mutation in the CFTR gene. [121][122][123] A placebo controlled crossover trial investigating the topical administration of gentamicin to the nasal epithelium for 14 days was conducted in patients who had one or two stop mutations or were homozygous for the F508del mutation.…”

Section: Related Therapeutic Effectsmentioning

confidence: 99%

New and emerging targeted therapies for cystic fibrosis

Quon

Rowe

2016

BMJ

121

122

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Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development.

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Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data

Abstract: These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis.

Cited by 215 publications

References 28 publications

Ivacaftor in cystic fibrosis adults: Czech experience with six years of follow-up

Ivacaftor in cystic fibrosis adults: Czech experience with six years of follow-up

Precision Medicine In Action: The Impact Of Ivacaftor On Cystic Fibrosis–Related Hospitalizations

New and emerging targeted therapies for cystic fibrosis

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