Results of European post-marketing surveillance of bosentan in pulmonary hypertension

¹ Dept of Pneumonology, Hopital Antoine Beclere, Clamart, France
² Global Drug Safety, Actelion Pharmaceuticals, Allschwil, Switzerland
³ Dept of Respiratory Medicine, Royal Hallamshire Hospital, Sheffield, UK
⁴ Medical Dept, Rigshospitalet, Copenhagen, Denmark
⁵ Global Medical Science, Actelion Pharmaceuticals, Allschwil, Switzerland
⁶ Dept of Respiratory Medicine, Medical School, Hanover, Germany

^* To whom correspondence should be addressed. E-mail: marc.humbert{at}abc.ap-hop-paris.fr.

	Abstract

After approval of bosentan for treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile.

We developed a novel, prospective, internet-based PMS, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events, and elevated aminotransferases.

Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. 4,623 patients were naïve to treatment; of these 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annualised rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 bosentan-naïve patients (3.2%). Safety results were consistent across subgroups and aetiologies.

The novel PMS captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials, and provide important additional information on the safety profile of bosentan.

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