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A Prospective Study to Describe Clinical and Tolerability Outcomes in Patients Transitioning From Bosentan or Ambrisentan to Macitentan

J. W. McConnell

Keith Robinson

Martha Royse

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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1051

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Purpose

Describe clinical and tolerability outcomes associated with switching patients from bosentan or ambrisentan to macitentan, utilizing functional class, 6 minute walk distance (6 MWD) and quality of life

Background

Pulmonary Arterial Hypertension (PAH) is a rare, progressive disorder characterized by remodeling of the pulmonary vasculature and a rise in right ventricular (RV) afterload, which in turn leads to RV enlargement, RV dysfunction and clinical symptoms (Barst 2004). There is no cure at present for PAH with nine agents currently approved by the FDA in the US for treatment. Macitentan is the most recently approved endothelin receptor antagonist (ERA) indicated to delay disease progression. It was shown to reduce hospitalizations and reduce morbidity and mortality. It is a once daily oral medication and does not require regular monitoring for toxicity, unlike other ERAs. Switching from bosentan to macitentan has previously been evaluated in a retrospective study (Safdar 2017).

Methods

In a prospective study, 21 patients were enrolled at a Pulmonary Hypertension Association accredited Center of Comprehensive Care and transitioned from background ERA of ambrisentan or bosentan to macitentan 10 mg and followed for one year. Safety labs, echocardiogram, 6MWD, functional class, Quality of Life utilizing SF-36 and Endothelin levels were measured during evaluation.

Results

Mean +/-SD age at the start of the trial was 66.9 +/- 10.49. Eighty-six percent of participants were female and 14 % were male. Nineteen percent of patients were on ambrisentan and 81 % on bosentan for background ERA therapy. Patients were all WHO group I, 67% idiopathic, 33% connective tissue disease. The mean time since diagnosis was 7 years +/- 3.78. Mean time on background ERA was 6.7 years +/- 3. At the beginning of the trial, 38% of patients were functional class II and 62% were functional class III. Eighteen (86%) patients completed the 12-month study. There were no drug related SAE’s. Thirty-three percent of patients did have a non-drug related SAE. Two patients had improved Functional Class from III to II and the rest of patients remained the same. Patients’ mean 6 MWD at baseline was 286.5 meters +/- 98.01. At one year, mean 6MWD was 275.5 meters +/- 110.60. The patients’ endothelin levels had no significant change over twelve months. Echocardiogram showed TAPSE had no significant change from baseline to week 24 and end of study. There was no statistically significant change in quality of life at end of study compared to baseline.

Conclusions

A rapid switch from bosentan and ambrisentan to macitentan was well tolerated in patients while functional class, 6 MWD, endothelin level and TAPSE remained stable. The patients’ quality of life was consistent from baseline to end of study. In a group of patients with a long term diagnosis of PAH, there was no significant deterioration over a period of twelve months.

References:

Barst RJ, McGoon M, Torbicki A, Sitbon O, Krowka MJ, Olschewski H, et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2004; 43 (12 Suppl S): 40S-7S.

Safdar Z, Thakur A, Frost A. Tolerability of switch to macitentan from bosentan in pulmonary arterial hypertension. South Med J. 2017 Mar; 110 (3):223-228.