ALLSCHWIL, Swtzerland and SAN ANTONIO, Texas, Oct. 18, 2004 (PRIMEZONE) -- Actelion Ltd. (PinkSheets:ALIOF): Studies reported at the American College of Rheumatology (ACR) support early diagnostic intervention -- Echocardiography and confirmatory right heart catheterization as appropriate tools.
Two new scientific studies released today at the American College of Rheumatology (ACR) are reporting a high prevalence of both diagnosed and undiagnosed pulmonary arterial hypertension (PAH) in patients with scleroderma and mixed connective tissue disease (MCTD).
The two studies -- sponsored by Actelion Ltd. (SWX:ATLN) -- were carried out in the United States and Europe. They are presented at a joint scientific poster presentation on Tuesday. On Monday, the official media activities of the conference organizer will also focus on the important role of early detection and treatment of PAH especially in these patients at high risk for developing this rapidly progressing and ultimately fatal disease (see media advisory at the end of this release).
The UNCOVER study: PAH in community rheumatology centers UNCOVER, is a U.S.-based study conducted in 50 community rheumatology centers sought to determine the prevalence of diagnosed and undiagnosed PAH. Based on the prevalence of PAH and PAH symptoms in the patients surveyed, the data suggests Echocardiogram evaluation of CTD patients treated in community rheumatology practices is justified.
The study findings in detail are:
-- A significant number of patients (15%) in community
rheumatology offices have a current diagnosis of pulmonary
arterial hypertension.
-- A significant number of patients (13.3 percent) in community
rheumatology offices have estimated right ventricular systolic
pressure (ERVSP) greater than 40 mmHg on Doppler
echocardiogram, which is highly suggestive of PAH making the
total population with diagnosed or suspected PAH 28.3%.
-- A significant number of patients not diagnosed with PAH with
ERSVP greater than 40 mmHg have corresponding symptoms
suggesting more advanced disease.
Nine hundred and nine patients with scleroderma or MCTD across 50 community rheumatology practices in the U.S (46) and Canada (4) participated in the study. Patients were 18 years of age or older and were diagnosed with scleroderma meeting the American College of Rheumatology (ACR) classification criteria for systemic sclerosis or had three to five features of the CREST syndrome.
Patients were assigned one of two groups. Those with an existing diagnosis of PAH were assigned to the retrospective group, with further data collection obtained from patients' existing medical record. Patients that did not have an existing diagnosis of PAH were assigned to the prospective group and invited to join the study. These patients had a Doppler echocardiogram of the right and left chambers (unless previously done in the last six months), and completed a dyspnea questionnaire rating severity.
ItinerAIR study: A French prevalence study
Conducted in France, the objective of the ItinerAIR Scleroderma study was to evaluate the prevalence of PAH in a French population with systemic sclerosis (SSc). The diagnosis followed a step-by-step approach, based on symptoms (dyspnea) and a pre-defined algorithm on echocardiography and required right heart catheterization (RHC) for confirmation of PAH diagnosis.
Consistent with UNCOVER, this study confirms the high prevalence of PAH in scleroderma and the validity of echocardiography as a screening modality. Furthermore, it highlights the importance of RHC as a confirmatory tool for diagnosis of PAH.
The study findings in detail are:
-- The prevalence of PAH in this French SSc population is
approximately 10%.
-- Cardiac catheterization remains the reference method for
confirming the diagnosis of PAH (the main differential
diagnosis is left heart disease).
-- A step-by-step diagnostic approach, starting at identifying
symptoms, followed by echocardiography and right heart
catheterization is an applicable approach in pragmatic
situations.
-- Increased age at scleroderma onset is a risk factor for PAH.
-- Diffuse scleroderma is not less at risk than limited
scleroderma, reinforcing the need for screening all
scleroderma patients for PAH.
-- Systematic screening allows diagnosis of PAH at a less severe
time point of the evolution of the disease.
The study was conducted in France at 21 university hospitals experienced in scleroderma management, and included multidisciplinary teams -- internists, dermatologists, rheumatologists, echo cardiographers and PAH specialists -- involving 100 investigators. The trial enrolled a total of 617 patients, approximately 10% of the estimated SSc population in France.
All scleroderma patients at the participating centers, including patients with known RCH-diagnosed PAH, were invited to participate in the study as part of their regular care. Those excluded from the study were patients with known severe pulmonary function abnormalities (FVC and/or TLC or FEV 3 m/s or greater than 2.5 m/s in the presence of dyspnea not explained by another cause. The full echocardiography data will be presented as a poster at AHA.
Professor Eric Hachulla, M.D., Hopital Claude Huriez, Lille/France said: "This study also shows that a multidisciplinary approach and an active screening of scleroderma patients allows for detection of PAH at an earlier stage, which may lead to improved prognosis through early intervention."
About Scleroderma
In systemic sclerosis (scleroderma), an autoimmune rheumatic disease, there is increased accumulation of connective tissue in skin and internal organs as well as vascular injury and damage. Complications including pulmonary arterial hypertension (PAH) and digital ulcers are the result of vasculopathy (vascular dysfunction). Endothelin, a pathogenic mediator, is implicated in vascular damage. In addition to causing vasoconstriction, Endothelin also has direct deleterious effects, which cause fibrosis, vascular hypertrophy, and inflammation.
About Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The function of the heart and lungs is severely compromised, manifested by a limited exercise capacity, and, ultimately, a reduced life expectancy. Approximately 100,000 people in Europe and the United States are afflicted with either primary or secondary forms of the disease related to conditions or tissue disorders that affect the lungs, such as scleroderma, lupus, HIV/AIDS or congenital heart disease.
About Tracleer(R) in Pulmonary Arterial Hypertension (PAH)
Tracleer(R), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) and made available by Actelion subsidiaries in the United States, the European Union, Australia, Canada and Switzerland. In Japan, Tracleer(R) has been filed for marketing approval.
In clinical trials leading to the marketing approval of the drug, approximately 11 % of PAH patients receiving Tracleer(R) experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take Tracleer(R).
Actelion Ltd.
Actelion Ltd. is a biopharmaceutical company with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug Tracleer(R) an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer(R) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -- the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).
Media Advisory:
Media invited to attend study preview at ACR/ARHP scientific meeting. The point prevalence of undiagnosed Pulmonary Hypertension (PAH) in patients with Connective Tissue Disease (CTD) attending community based Rheumatology clinics (Uncover study)
Media Session Scheduled for October 18; Poster Session To Follow on October 19
WHAT: Presentation for media at American College of
Rheumatology's annual conference (ACR/ARHP Scientific
Meeting) previewing Uncover Study results; poster session
to follow the next day.
Uncover Study -- The Point Prevalence of Undiagnosed Pulmonary Hypertension (PAH) in Patients with Connective Tissue Disease (CTD) Attending Community Based Rheumatology Clinics
PAH is a major cause of morbidity and mortality among patients with scleroderma (SSc) and mixed connective tissue disease (MCTD), yet physicians often do not detect its presence until the late stages of disease. Most prevalence data come from University or tertiary centers which are biased toward severe disease; therefore the true prevalence of PAH among patients with CTD is unknown. The study sought to determine the point prevalence of undiagnosed PAH in community-based rheumatology practices in the USA and Canada.
WHO: Frederick M. Wigley, John Hopkins University WHEN: Media Presentation Poster Session Monday, October 18 Tuesday, October 19 1:30 p.m. - 2:30 p.m. 12:15 p.m. - 2:00 p.m. WHERE: ACR/ARHP Annual Scientific Meeting Henry B. Gonzales Convention Center, San Antonio, TX