P260 Adverse drug reactions and discontinuation rate during the first year on Orkambi - the earliest results of the STORM study

Brokaar, Edwin J.; Leeuwen, Marieke van; Leegwater, Emiel; Ploeger, M.; Meer, R.B. Van Der

doi:10.1016/s1569-1993(19)30553-3

Cited by 3 publications

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“…The majority of AEs reported with LUM/IVA were respiratory-related. Chest tightness, dyspnea, increased sputum, and declines in ppFEV 1 were among the most common respiratory AEs and tended to occur within the first few days after initiation, even as quickly as 3–4 h after the first dose [ 25 , 26 , 27 , 31 , 32 , 33 , 34 , 35 , 37 , 38 , 41 , 42 , 43 , 44 , 45 , 60 , 61 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 83 , 84 , 85 , 90 ]. Bronchodilators were beneficial in mitigating symptoms of chest tightness, wheeze, and increased work of breathing in some individuals [ 31 , 41 , 66 , 67 , 75 ].…”

Section: Resultsmentioning

confidence: 99%

“…ppFEV 1 could take upwards of three months after initiation to recover to baseline values [ 34 , 43 ]. Increased cough was common, sometimes resulting in discontinuation [ 33 , 42 , 44 , 45 , 69 , 73 , 76 , 85 ], while chest pain was infrequently reported [ 37 , 45 , 72 , 85 ]. Two cases of hemoptysis and one case of pneumothorax reportedly caused discontinuation of LUM/IVA in one study; whether the hemoptysis and pneumothorax were attributable to underlying disease was not specified [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…Similarly common with LUM/IVA were gastrointestinal AEs, of which abdominal pain, nausea and/or vomiting, and diarrhea were the most frequently reported and resulted in discontinuation in two studies each [ 26 , 33 , 34 , 42 , 44 , 45 , 61 , 69 , 71 , 73 , 78 , 79 , 85 ]. Uncommon gastrointestinal AEs were dysphagia and decreased appetite; the one case of dysphagia resulted in discontinuation [ 44 , 61 ].…”

Section: Resultsmentioning

confidence: 99%

“…Headache and fatigue were reported relatively often overall but were not a common cause of LUM/IVA discontinuation [ 25 , 26 , 33 , 34 , 42 , 45 , 69 , 73 , 76 ]. Menstrual irregularities and menorrhagia were reported infrequently but did result in discontinuation of LUM/IVA—the former in one patient who also discontinued due to worsening anxiety [ 47 ], and the latter in three individuals (0.4%) in a large cohort [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

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Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Dagenais

Quon

2020

JCM

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Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Dagenais

Quon

2020

JCM

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“…Gastrointestinal side effects such as diarrhea, nausea and abdominal pain in addition to breathlessness have been reasons for discontinuation. In a real-world setting, 14% of patients discontinued medication within a year of starting treatment and in two-thirds of cases, this was reported as being due to adverse drug reactions 38…”

Section: Introductionmentioning

confidence: 99%

<p>Lumacaftor-ivacaftor in the treatment of cystic fibrosis: design, development and place in therapy</p>

Connett

2019

DDDT

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Lumacaftor-ivacaftor is a combination of two small molecule therapies targeting the basic defect in cystic fibrosis (CF) at a cellular level. It is a precision medicine and its effects are specific to individuals with two copies of the p.Phe508del gene mutation. The drug combination works by restoring functioning CF transmembrane conductance regulator (CFTR) protein in cell surface membranes and was the first CFTR modulator licensed for the homozygous p.Phe508del genotype. The drug is a combination of a CFTR corrector and potentiator. Lumacaftor, the corrector, works by increasing the trafficking of CFTR proteins to the outer cell membrane. Ivacaftor, the potentiator, works by enabling the opening of what would otherwise be a dysfunctional chloride channel. In vivo lumacaftor-ivacaftor improves Phe508del-CFTR activity in airways, sweat ducts and intestine to approximately 10–20% of normal CFTR function with greater reductions in sweat chloride levels in children versus adults. Its use results in a modest improvement in lung function and a decreased rate of subsequent decline. Perhaps more importantly, those treated report increased levels of well-being and their rate of respiratory exacerbations is significantly improved. This review traces the development and use of this combination of CFTR modulators, the first licensed drug for treating the homozygous p.Phe508del CF genotype at the intracellular level by correcting the protein defect.

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Clinical Efficacy and Safety of Ivacaftor/Lumacaftor Combination in Patients with Cystic Fibrosis: International Studies Review

Kashirskaya

Petrova

Зинченко

2021

Vopr. sovr. pediatr.

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Cystic fibrosis is an autosomal recessive disease caused by structure abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is characterized by severe course and poor prognosis without or with insufficient treatment. Approval of pathogenetic therapy medications, CFTR modulators (potentiators and correctors), for clinical use in 2012 in the United States has reduced mortality from this disease. This article provides the overview of studies on clinical efficacy and safety of ivacaftor/lumacaftor combination (Iva/Lum) — the first licensed CFTR modulator medication for homozygous patients with F508del variant. It was shown that Iva/Lum increases lung function, reduce the number of acute conditions of bronchopulmonary process (including those that require antibiotics and hospitalization), partially restores pancreas exocrine function, increases body weight and mass growth index, and improves quality of life. It allows considering it as favorable effect on the course and prognosis of cystic fibrosis. It was also noted that the early onset of the drug administration (from the age of two) positively affects the prognosis of the disease, increasing life expectancy and improving quality of life.

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P260 Adverse drug reactions and discontinuation rate during the first year on Orkambi - the earliest results of the STORM study

Cited by 3 publications

References 0 publications

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

<p>Lumacaftor-ivacaftor in the treatment of cystic fibrosis: design, development and place in therapy</p>

Clinical Efficacy and Safety of Ivacaftor/Lumacaftor Combination in Patients with Cystic Fibrosis: International Studies Review

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