Tracleer and PPH News Long-Term Survival Using Tracleer for PH Faces Scrutiny
by John C. Martin
03-04-2005 - A new, oral medication approved as a therapy for primary pulmonary hypertension (PPH) was tested recently in a large study, and the physicians who participated concluded the drug improved survival for patients as compared to the odds they might have faced with no treatment.1 3-Year Survival Odds Using Bosentan
Vallerie McLaughlin, MD, an associate professor of Internal Medicine at the University of Michigan and a team of investigators assessed the long-term benefit of bosentan, marketed as Tracleer (Actelion Pharmaceuticals) in a group of 169 patients who had taken part in two placebo-controlled clinical trials. The patients were followed for more than 3 years, beginning at the start of the first placebo-controlled trial. The investigators compared the survival chances of each patient taking bosentan versus those of each patient if they had not taken any treatment, based on clinical experience and National Institutes of Health (NIH) data. "Survival estimates [with bosentan] were 96% at 12 months and 89% at 24 months, respectively" wrote McLaughlin and her team. "In contrast, predicted survival [without treatment] was 69% and 57%, respectively." After 2 years of follow-up, 70 percent of patients were still taking bosentan alone, without the need for additional therapies. Treatment with the oral drug was well tolerated, the researchers reported, although they did note a 10% increased incidence of elevated liver enzymes, thereby requiring monthly liver enzyme monitoring. (Increased liver enzymes are indicators that liver damage may have occurred.) McLaughlin's group found that indicators of the worse prognosis in any one patient were end-stage PH (NYHA functional class IV) and a reduced walking distance in a standard 6-minute test. Bosentan was approved by the FDA in 2001 to improve exercise ability and reduce disease progression in people with pulmonary hypertension. It is an oral medication, classified as a endothelin receptor antagonist (ERA). ERAs work by blocking endothelin-1, a hormone that plays a role in narrowing blood vessels. Researchers have found increased levels of endothelin-1 in the lung tissue and plasma of PH patients, suggesting it plays a role in the pathology of the disease.2 'Longer Information Will Be of Interest'
In an editorial related to the study,3 Marc Humbert, MD, in the Service de Pneumologie at Hôpital Antoine-Béclère in Clamart, France notes several limitations of this study admitted by the authors. "Presumably, subjects selected for randomized studies have a better general condition and standard of care than patients treated 20 years ago," Humbert wrote. "Therefore, survival estimated in the 1980s with the NIH [data used in this study] is certainly a pessimistic comparator." "Nevertheless, the NIH equation has been validated and still represents the best available tool for comparative studies," he added. Humbert also noted that the exposure to the drug was relatively short in this study, "and longer information will be of interest to determine whether add-on or switch to another class of drug is required in the long term, and what the exact prognosis of these patients is." Other Trials Needed
Finally, Humbert emphasized that there is a significant need for long-term observational studies of all the medications currently available for PH (Flolan/GlaxoSmithKline, Remodulin/United Therapeutics and bosentan) in terms of their effects on survival and quality of life, their side effects, and their costs. "As head-to-head comparisons of currently approved therapies are not available, the choice of optimal treatment will be dictated by clinical experience and drug availability, as well as patient preference." 1. McLaughlin VV, Sitbon O, Badesch DB et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005 Feb;25(2):244-9.
2. Popa A. Center for Continuing Education. The Cleveland Clinic. Bosentan (Tracleer), a new agent for the treatment of pulmonary arterial hypertension. Available at: https://www.clevelandclinicmeded.com/medical_info
/pharmacy/marapr2002/bosentan.htm. Accessed March 3, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
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