Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan, a dual endothelin-1 receptor antagonist, on symptomatology, haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD), NYHA functional class, Borg Dyspnoea Index (BDI) and SF-36 were measured at 0, 3, 6, 9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero, six and 12 months. Clinical parameters were analysed, pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m, +26.2 m, +54 m and +62.7 m at three (P = 0.001), six (P = 0.001), nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class, BDI, transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health, vitality, social function and general health. Significantly deranged liver function was found in one patient. Lupus (2007) 16, 279—285.

Keywords

echocardiography endothelin-1 pulmonary hypertension survival

Get full access to this article

View all access options for this article.

References

Tanaka E. , Harigai M. , Tanaka M. , Kawaguchi Y. , Hara M. , Kamatani N. Pulmonary hypertension in systemic lupus erythematosus: evaluation of clinical characteristics and response to immunosuppressive treatment. J Rheumatol 2003; 29: 282—287.

Pan TL , Thumboo J. , Boey ML Primary and secondary pulmonary hypertension in systemic lupus erythematosus . Lupus 2000; 9: 338—342.

Shen JY , Chen SL , Wu YX et al. Pulmonary hypertension in systemic lupus erythematosus. Rheumatol Int 1999; 18: 147—151.

Galie N. , Manes A. , Farahani KV et al. Pulmonary arterial hypertension associated to connective tissue diseases. Lupus 2005; 14: 713.

D'Alonzo GE , Barst RJ , Ayres SM et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343—359.

Galie N. , Torbicki A. , Barst R. et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The task force on diagnosis and treatment of pulmonary arterial hypertension of the European Society of Cardiology. Eur Heart J 2004; 25: 2243—2278.

Rubin LJ , Badesch DB , Barst RJ et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346: 1259.

Channick RN , Simonneau G. , Sitbon O. et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized placebo-controlled study . Lancet 2001; 358: 1119—1123.

Denton CP , Humbert M. , Rubin L. , Black CM Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann Rheum Dis 2006; 65: 1336—1340.

10.

Braun-Moscovici Y. , Nahir AM , Balbir-Gurman A. Endothelin and pulmonary arterial hypertension . Semin Arthritis Rheum 2004; 34: 442—53.

11.

Cozzi F. , Montisci R. , Marotta H. et al. Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases. Eur J Clin Invest 2006; 36(Suppl 3): 49—53.

12.

Sharma S. , Kashour T. , Philipp R. Secondary pulmonary arterial hypertension treated with endothelin receptor blockade. Tex Heart Inst J 2005; 32: 405—410.

13.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271—1277.

14.

Lam Clk , Lauder IJ , Lam TP , Gandek B. Population based norming of the Chinese (HK) version of the SF-36 health survey . Hong Kong Practitioner 1999; 11: 460—470.

15.

Hachulla E. , Coghlan JG A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism. Annals Rheum Dis 2004; 63: 1009—1014.

16.

Kawut SM , Taichman DB , Archer-Chicko CL , Palesky HI , Kimmel SE Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003; 123: 344—350.

17.

Miyamato S. , Nagaya N. , Satoh T. et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000; 161: 487—492.