Effects of Ivacaftor in Patients With Cystic Fibrosis Who Carry the G551D Mutation and Have Severe Lung Disease

Barry, Peter J.; Plant, Barry J.; Nair, Arjun; Bicknell, Stephen; Simmonds, Nicholas J.; Bell, Nicholas; Shafi, Nadia; Daniels, T.; Shelmerdine, Susan C.; Felton, Imogen; Gunaratnam, Cedric; Jones, Andrew M.; Horsley, Alex

doi:10.1378/chest.13-2397

Cited by 87 publications

(62 citation statements)

References 12 publications

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“…Similar events were not described with ivacaftor monotherapy [3,5], so the respiratory adverse events described here are almost certainly related to lumacaftor. In the phase 2 trials, there was also a dose related decrement in FEV 1 in the lumacaftor monotherapy arm [4].…”

supporting

confidence: 71%

“…Hubert however reports that in those who tolerate and continue treatment, similar lung function improvements to that in the clinical trials can be achieved, with an absolute increase of 5% in FEV 1 seen in a third of patients [2]. Ultimately, lung function changes may not be as important as establishing the effect on exacerbations, which was the clearest demonstration of benefit for a severe Gly551Asp cohort treated with ivacaftor [5].…”

mentioning

confidence: 90%

“…Popowicz speculates that the phenomenon may instead be due to changing hydration of the airway mucus [1]. Whilst this may be contributory, it doesn't explain why the same tightness was absent in Gly551Asp patients treated with ivacaftor [5]. Nor has this featured in the early reports of the pipeline modulator VX-661 (tezacaftor), which restores CFTR function to a similar level [8] and in a recent press release seems to be at least as effective at improving FEV 1 .…”

mentioning

confidence: 99%

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Orkambi in patients with severe disease — Bumps in the road to CFTR modulation

Horsley

Barry

2017

Journal of Cystic Fibrosis

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supporting

confidence: 71%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Orkambi in patients with severe disease — Bumps in the road to CFTR modulation

Horsley

Barry

2017

Journal of Cystic Fibrosis

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“…This condition was not included in the above mentioned clinical studies. There are some papers describing case reports or small groups of severe airway obstruction patients who profited from ivacaftor therapy 20,21 . However, the response to treatment appeared to be inconsistent 22 .…”

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

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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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“…Importantly, post-licensing studies have also highlighted the potential for improvement in lung function for patients with severe lung disease who were excluded from the original trial. A multi-centre retrospective study of patients with severe lung disease who carried the G551D mutation and received ivacaftor therapy on a compassionate use programme demonstrated improvements in lung function and weight and, perhaps most importantly, significant reductions in time spent receiving intravenous antibiotics [22].…”

Section: Cftr Potentiatorsmentioning

confidence: 99%

New and Emerging Treatments for Cystic Fibrosis

Barry¹,

Jones²

2015

Drugs

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Recently, a significant number of additional key medications have become licensed in Europe for the treatment of patients with cystic fibrosis (CF), including a number of inhaled antibiotics, such as nebulised aztreonam and dry powder versions of colistin and tobramycin for inhalation; dry powder inhaled mannitol, an agent to improve airway hydration and aid airway clearance; and ivacaftor, an oral therapy that directly acts on dysfunctional CFTR to correct the basic defect encountered in CF patients with the G551D CF gene mutation. The marked success of ivacaftor both in clinical trials and in post-licensing evaluation studies in treating patients with G551D and other gating mutations has greatly encouraged the ongoing development of similar therapies that can directly target the underlying cause of CF. Other therapies, including a number of anti-infectives, anti-inflammatories and replacement pancreatic enzymes, are currently undergoing clinical studies. This article reviews those treatments that have been recently licensed for CF and highlights some of the exciting emerging therapies presently under evaluation in clinical trials. In addition, it discusses some of the potential challenges being encountered by research and clinical teams in developing and delivering treatments for this condition.

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Effects of Ivacaftor in Patients With Cystic Fibrosis Who Carry the G551D Mutation and Have Severe Lung Disease

Cited by 87 publications

References 12 publications

Orkambi in patients with severe disease — Bumps in the road to CFTR modulation

Orkambi in patients with severe disease — Bumps in the road to CFTR modulation

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

New and Emerging Treatments for Cystic Fibrosis

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