Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension

Aypar, Ebru; Alehan, Dursun; Karagöz, Tevfik; Aykan, Hayrettin Hakan; Ertuğrul, İlker

doi:10.1017/s1047951117002542

Cited by 17 publications

(19 citation statements)

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“…Currently there is only limited experience on the use of macitentan in children. Available data include one smaller study in children older than 12 years 17 and a recently published work by Flores et al. 18 reporting on their initial experience of macitentan in two smaller children.…”

Section: Discussionmentioning

confidence: 99%

“…13–15 Whereas clinical trials and case reports in adults support its efficacy and tolerability, data on children are limited. 16–18,21–27…”

Section: Discussionmentioning

confidence: 99%

“…16 Experience on its use in children is scarce. 17,18 This issue is actually faced by a large randomized multicentre open label study (TOMORROW study AC-055-312), which hopefully will lead to license of this drug in childhood. However, in many cases, severity of the disease forces paediatricians to implement medications without approval, before escalating therapy to more invasive therapeutical options such as intravenous or subcutaneous prostacyclines, Potts shunt or lung transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

et al. 2021

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Macitentan is a safe and effective substance for treatment of adults with pulmonary arterial hypertension. Data on its use in paediatric patients is limited. In this single centre prospective study we report on our experience with macitentan in children focusing on applicability and practical aspects. Between 12/2014 and 07/2018 macitentan was introduced to paediatric patients according to a dosing protocol adjusted to body weight. Blood pressure, heart rate, saturation and clinical symptoms were recorded daily during introduction. Liver function parameters and haemoglobin levels were measured at baseline, 4 weeks and 3 months after initiation and after one year of treatment. 24 patients (14 male, 10 female) were enrolled for treatment with macitentan. The mean age was 10.7 +/- 7.6 years (range 0.1 y â 23 y). 15/24 pts were WHO FC II, 7 pts in FC III and 2 pts in FC IV. 20/24 patients (83%) received additional advanced therapy with sildenafil and /or prostacyclines. We had two early discontinuations because of clinical relevant edema. In the remaining 22 patients macitentan was well tolerated. Liver function parameters and blood count levels remained stable during the observational time. The introduction of macitentan was feasible and mostly well tolerated in paediatric patients. Special attention should be paid to edema during introduction of the drug. To the best of our knowledge, this is the first prospective observational study to report on its applicability in infants and children. However larger prospective trials are warranted to verify these preliminary findings.

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Section: Discussionmentioning

confidence: 99%

“…13–15 Whereas clinical trials and case reports in adults support its efficacy and tolerability, data on children are limited. 16–18,21–27…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

et al. 2021

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“…Кроме того, среди трех зарегистрированных в настоящее время АРЭ бозентан обладает наибольшим гепатотоксическим потенциалом, из-за которого препарат не может рассматриваться в качестве препарата первого ряда для пациентов с недавно диагностированной ЛАГ. Напротив, новый неселективный тканеспецифичный препарат мацитентан в дозе 10 мг не только подтвердил свою эффектив-ность у больных ЛАГ в качестве монотерапии, но и в комбинации с силденафилом [15]. Препарат обладает хорошим спектром безопасности и не имеет ранее описанных для этого класса препаратов гепатотоксических эффектов или клинически значимых лекарственных взаимодей ствий.…”

Section: Discussionunclassified

Experience of Using the Nonselective Endothelin Receptor Antagonist Macitentan in Patients With Pulmonary Arterial Hypertension

Симакова

Гончарова

Karelkina

et al. 2018

Cardiovasc Ther Prev

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Aim. To present the results of treatment with macitentan of patients included in the clinical trial SERAPHIN in Almazov National Medical Research Centre and define target therapy of pulmonary arterial hypertension (PAH) in real clinical practice.Material and methods. The article presents the results of the 151 patients with PAH followedup in Almazov National Medical Research Centre from 2009 to 2016.Results. Fiveyear survival of PAH patients included in the register of Almazov National Medical Research Centre reached 77% for idiopathic PAH, 52% for PAH associated with systemic scleroderma, 81% for PAH associated with nonrepaired congenital heart disease, 82% for patients with repaired congenital shunts and 100% for PAH associated with human immunodeficiency virus infection. The group that received PAH specific monotherapy consisted of 47% (n=71) of patients among which phosphodiesterase type 5 inhibitor (PDE5i) sildenafil was undoubtedly the most prescribed drug — 74% (n=53). The group that received combined PAH specific therapy consisted of 66 (44%) patients: 48 patients received various twocomponent therapy, 18 patients — threecomponent therapy with endothelin receptor antagonist in combination with PDE5i and prostanoids. 11 patients with PAH were included in SERAPHIN study of which 9 patients had been already receiving generic PDE5i therapy. In macitentan group, a statistically significant increase in the 6minute walk distance (+50 meters) and a decrease in hemodynamic parameters such as mean right atrial pressure (2,3 mm Hg) and pulmonary vascular resistance (445 dynsec/cm5) were observed after 6 months. No patient had a clinically significant increase in liver transaminases or a decrease in hemoglobin levels.Conclusion. Improvement of prognosis in PAH patients according to the register of the Centre is connected both with early detection of the disease, thanks to the development of specialized healthcare, and more frequent use of combination therapy. Macitentan proved its longterm efficacy and safety as monotherapy and in combination with PDE5i.

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“…17,18 We have recently reported that switch from bosentan to macitentan significantly improved exercise capacity in children and young adults with pulmonary arterial hypertension in a 24-week prospective study and well tolerated without adverse events. 19 We now aimed to evaluate clinical efficacy, safety of switch from bosentan to macitentan in a larger patient population and in a 24-month prospective study due to desirable features (once-a-day profile and freedom from monthly liver function tests) of macitentan.…”

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confidence: 99%

Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension: extended study results

et al. 2020

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Background:Macitentan is an orally active, potent, dual endothelin receptor antagonist and is the only registered treatment for pulmonary arterial hypertension that significantly reduced morbidity and mortality in a long-term study.Aim:We have recently reported that switch from bosentan to macitentan significantly improved exercise capacity in children and young adults with pulmonary arterial hypertension in a 24-week prospective study and well tolerated without adverse events. We now aimed to evaluate clinical efficacy, safety of switch in a larger patient population, in a 24-month prospective study.Methods:This is a single-institution, 24-month prospective study. Patients ≥12 years with idiopathic/heritable, pulmonary arterial hypertension, or related to CHD or residual pulmonary arterial hypertension due to repaired congenital systemic-to-pulmonary shunts and on bosentan treatment were included. Concomitant treatment with oral phosphodiesterase type 5 inhibitors/inhaled prostanoids was allowed. Outcome measures included change from baseline to 24 months, in the 6-minute walk distance, functional class, oxygen saturation at rest/after walk distance test, and natriuretic peptide levels. Safety end points included adverse events, laboratory abnormalities.Results:Twenty-seven patients (19 adults/8 children, mean age: 21.1 ± 6.3 years (12–36), weight: 53.1 ± 15.7 kgs (26–87)) were included. Mean duration of macitentan treatment: 22.3 ± 3.9 months (9–24). Six-minute walk distance significantly improved from baseline (mean: 458 ± 79 m (300–620)) at 6 months (mean: 501 ± 73 m (325–616) + 43 m) (p < 0.05), at 12 months (mean: 514 ± 82 m (330–626) + 56 m) (p < 0.05), and at 24 months (mean: 532 ± 85 m (330–682) + 74 m) (p < 0.05). We observed a significant improvement during the first 6 months but no incremental improvement after 6 months (p > 0.05). Macitentan did not significantly change functional class, oxygen saturation, and natriuretic levels (p > 0.05). None of the patients had anaemia, hepatotoxicity, and peripheral edema.Conclusions:Our study is the first study which showed that switch from bosentan to macitentan improved exercise capacity in children and young adults with pulmonary arterial hypertension significantly in the first 6 months and compared to baseline in 24 months and well tolerated without adverse events.

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Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension

Abstract: Our study is the first study that showed that switch from bosentan to macitentan significantly improved exercise capacity in children and young adults with pulmonary arterial hypertension and is well tolerated without any adverse events.

Cited by 17 publications

References 17 publications

Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

Experience of Using the Nonselective Endothelin Receptor Antagonist Macitentan in Patients With Pulmonary Arterial Hypertension

Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension: extended study results

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Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension

Abstract: Our study is the first study that showed that switch from bosentan to macitentan significantly improved exercise capacity in children and young adults with pulmonary arterial hypertension and is well tolerated without any adverse events.

Cited by 17 publications

References 17 publications

Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

Macitentan in infants and children with pulmonary hypertensive vascular disease. Feasibility, tolerability and practical issues – a single‐centre experience

Experience of Using the Non­selective Endothelin Receptor Antagonist Macitentan in Patients With Pulmonary Arterial Hypertension

Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension: extended study results

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Experience of Using the Nonselective Endothelin Receptor Antagonist Macitentan in Patients With Pulmonary Arterial Hypertension