An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor

Jennings, Mark T.; Dezube, Rebecca; Paranjape, Shruti; West, Natalie E.; Hong, Gina; Braun, Andrew T.; Grant, Jonathan J.; Merlo, Christian A.; Lechtzin, Noah

doi:10.1513/annalsats.201701-058oc

Cited by 64 publications

(67 citation statements)

References 8 publications

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“…Treatment benefits in patient with ppFEV 1 b 40 were consistent with the overall patient population; however, an increased incidence of respiratory events, including dyspnea and chest tightness, were observed [7]. In the clinical practice setting, there have been reports of increased frequency in respiratory adverse events (AEs) in patients with ppFEV 1 b 40 initiating treatment with LUM/IVA [8][9][10]. This study evaluated the safety and efficacy of LUM/IVA in patients with CF who were homozygous for the F508del-CFTR mutation and had advanced lung disease (ppFEV 1 b 40) in a prospective, open-label, 24-week clinical study.…”

Section: Introductionmentioning

confidence: 76%

Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR

Taylor‐Cousar

Jain

Barto

et al. 2018

Journal of Cystic Fibrosis

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Section: Introductionmentioning

confidence: 76%

Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR

Taylor‐Cousar

Jain

Barto

et al. 2018

Journal of Cystic Fibrosis

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“…This analysis showed an increase (versus placebo) of 3.7 and 3.3 percentage points over placebo in the two dosing groups ( p=0.024 and 0.036, respectively) and a 9.9-9.1% relative increase in FEV 1 % pred, also highly clinically significant. Body mass index increased significantly only in one of [16][17][18][19][20]. Collectively, these case series report a reduction in exacerbation frequency.…”

Section: Efficacy Of Cftr Modulators In People With Advanced Pulmonarmentioning

confidence: 86%

Impact of CFTR modulator use on outcomes in people with severe cystic fibrosis lung disease

Shteinberg

Taylor‐Cousar

2020

Eur Respir Rev

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Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug–drug interactions, are discussed.

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“…To see if an increase in patients' number could yield a different result, we extended the analyses of clinical parameters to 20 other patients, however resulting in no statistically significant changes. Our cohort of 34 patients comprises subjects with a broad respiratory function at the baseline (from 21 to 118 FEV 1 %), and this may constitute a big difference with phase 3 studies, in which patients were initially excluded if their baseline lung function (FEV1%) was less than 40%, as also has been observed in a recent observational study [31]. Again, this consideration indicates conducting observational studies in a higher number of patients with more homogenous clinical status.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi®) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells

Favia

Gallo

Guerra

et al. 2020

IJMS

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The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi®, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi® in a small cohort of F508del/F508del patients (n = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV1%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi® treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV1%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi® treatment in CF patients.

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An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor

Abstract: This study highlights the prevalence of adverse effects in a CF population newly exposed to lumacaftor/ivacaftor and demonstrates a relatively high rate of drug intolerance.

Cited by 64 publications

References 8 publications

Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR

Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR

Impact of CFTR modulator use on outcomes in people with severe cystic fibrosis lung disease

Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi®) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells

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