Pulmonary arterial hypertension associated
with connective tissue disease

Pulmonary arterial hypertension (PAH) is a significant comorbidity of connective tissue disease (CTD)1

Patients with systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are at risk of developing pulmonary arterial hypertension^2,3

	8% to 27% of patients with SSc may also have PAH.1
	As many as 25% of patients with MCTD may also have PAH.4

PAH is a less common but devastating complication of lupus

	Prevalence of PAH in systemic lupus erythematosus (SLE): 0.5% to 14%2,3
	In a 5-year follow-up study of PAH in 28 patients with SLE, the prevalence of PAH increased from 14% at the first study to 43% at follow-up.5

Annual screening with echocardiography is recommended for all patients with SSc^1,4

In the UNCOVER study, 791 CTD patients in community-based rheumatology practices were screened for the presence of PAH4:

*For purposes of the study, an estimated right ventricular systolic pressure (ERVSP) ≥40 mm Hg was considered PAH.⁴
†Advanced disease was defined as ERVSP ≥50 mm Hg, increased right ventricular dimensions, or right atrial enlargement.⁴

More than 100 PAH-CTD patients evaluated in 3 Tracleer pivotal studies^6-8

EARLY: n=33 (N=185)

Study 351: n=5 (N=32)

BREATHE-1: n=63 (N=213)

There were no apparent differences in treatment effects among subgroups, as the studies were not designed to detect such differences.

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter.

High potential for major birth defects—Pregnancy must be excluded and prevented through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review PAH–SSc screening and diagnosis

1. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension. J Am Coll Cardiol. 2009;53:1573-1619.
2. Pope J. An update in pulmonary hypertension in systemic lupus erythematosus—do we need to know about it? Lupus. 2008;17:274-277.
3. Haas C. Pulmonary hypertension associated with systemic lupus erythematosus. [In French]. Bull Acad Natl Med. 2004;188:985-997.
4. Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C. The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study). Arthritis Rheum. 2005;52:2125-2132.
5. Winslow TM, Ossipov MA, Fazio GP, Simonson JS, Redberg RF, Schiller NB. Five-year follow-up study of the prevalence and progression of pulmonary hypertension in systemic lupus erythematosus. Am Heart J. 1995;129:510-515.
6. Galiè N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371:2093-2100.
7. Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119-1123.
8. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.