Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis

Labaste, A.; Ohlmann, Camille; Mainguy, Catherine; Jubin, V.; Perceval, M.; Coutier, Laurianne; Reix, Philippe

doi:10.1016/j.jcf.2017.05.002

Cited by 17 publications

(18 citation statements)

References 9 publications

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“…When comparing post-dose versus pre-dose spirometry measurements in the current studies no significant differences were observed, indicating a lack of bronchoconstriction. This is reassuring as such effects (chest tightness, dyspnea) have been reported in some subjects and healthy volunteers receiving their first administration of lumacaftor/ivacaftor [7,8,21,22]. There were no permanent discontinuations of GLPG2222 due to TEAEs in either of the present studies.…”

Section: Discussionsupporting

confidence: 79%

CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials

Bell

Barry

Boeck

et al. 2019

Journal of Cystic Fibrosis

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a b s t r a c tBackground: Several treatment approaches in cystic fibrosis (CF) aim to correct CF transmembrane conductance regulator (CFTR) function; the efficacy of each approach is dependent on the mutation(s) present. A need remains for more effective treatments to correct functional deficits caused by the F508del mutation. Methods: Two placebo-controlled, phase 2a studies evaluated GLPG2222, given orally once daily for 29 days, in subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS). The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms. Results: Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6 mmol/L [GLPG2222 200 mg], p b 0.0001; ALBATROSS: -7.4 mmol/L [GLPG2222 300 mg], p b 0.05). No significant effects on pulmonary function or respiratory symptoms were reported. Plasma GLPG2222

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Section: Discussionsupporting

confidence: 79%

CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials

Bell

Barry

Boeck

et al. 2019

Journal of Cystic Fibrosis

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“…Following LUM/IVA dosing on day 1, participants' mean post-dose FEV 1 % pred was −5.5% at ⩽2 h, −7.7% at 4-6 h and −4.1 at 24 h [26]. A real-life study similarly found an acute drop in lung function in LUM/IVA-treated children aged 15.5±1.6 years with a wide range of initial lung function, which was inversely correlated with initial FEV 1 % pred and directly correlated with bronchodilator reversibility [27].…”

Section: Adverse Events Resulting From Cftr Modulator Therapy In Peopmentioning

confidence: 70%

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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“…Improvements in lung function in patients homozygous for F508del were generally comparable to or numerically greater than those observed in patients treated with lumacaftor/ivacaftor in the phase 3, 24-week TRAFFIC/TRANSPORT studies (26). Treatment initiation with lumacaftor/ivacaftor is sometimes associated with respiratory events and acute lung function decline (26)(27)(28)(29)(30), which can restrict the number of patients willing to start treatment. The improved benefit-to-risk profile makes tezacaftor/ivacaftor a potential treatment option for a greater proportion of patients homozygous for F508del.…”

Section: Discussionmentioning

confidence: 88%

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR

Donaldson

Pilewski

Griese

et al. 2018

Am J Respir Crit Care Med

155

147

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Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis

Cited by 17 publications

References 9 publications

CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials

CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials

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

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR

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