Send letter to journal:
Re: Treatment of PAH associated with connective tissue disease

Dear Editor, I read with interest the manuscript, by Girgis et al (1) on the role of sitaxsentan in the treatment of patients with pulmonary arterial hypertension associated with connective tissue diseases. The main conclusion is that sitaxsentan, a selective endothelin-A receptor antagonist, produced a significant improvement in six-minute walk distance, functional class, and quality of life in this group of patients.

The authors are to be congratulated on highlighting this group of patients and they have done a good job of outlining the potential shortcomings of a small post-hoc analysis. As described by the authors, patients with pulmonary hypertension associated with scleroderma are known to have very poor outcomes despite vasodilator therapy (2-4), as such this finding can have significant implications. The bulk of data in this arena though, comes from patients with pulmonary hypertension related to scleroderma (2-4) and there is very little information on treatment responses in patients with pulmonary hypertension related to other connective tissue diseases.

We have recently reported that patients with systemic lupus erythematosus and pulmonary hypertension may have a much more favorable short- and long-term response to vasoactive therapy (5). Similar findings have also been reported previously in smaller case series (6,7). In contrast to patients with scleroderma, there are also reports of severe pulmonary hypertension in patients with systemic lupus erythematosus responding to immunosuppressive therapy (8,9). It is not unreasonable to assume that response to therapy and outcomes in patients with pulmonary hypertension related to different diseases may be different and, in view of their distinctly different responses, perhaps we should avoid grouping them together under the rubric of “pulmonary hypertension associated with connective tissue diseases”. The small sample size may not have allowed the authors to do so, however, it would be interesting to contrast the response to therapy in patients with scleroderma and systemic lupus erythematosus among their cohort since a sizable proportion of the patients had systemic lupus erythematosus. I would argue in favor of tempered enthusiasm until further studies confirm that patients with pulmonary hypertension associated with scleroderma have short- and long-term outcomes, similar to patients with idiopathic pulmonary arterial hypertension, on vasoactive therapy.

References

1. Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, Mclaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ. Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis 2007 Epub ahead of print.

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

3. Oudiz RJ, Schilz RJ, Barst RJ, Galie N, Rich S, Rubin LJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue diseases. Chest 2004;126:420-427.

4. Girgis RE, Mathai SC, Krishnan JA, Wigley FM, Hassoun PM. Long-term outcome of bosentan treatment in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with scleroderma spectrum of diseases. J Heart Lung Transplant 2005;24:1626-1631.

5. Heresi GA, Minai OA. Lupus-associated pulmonary hypertension: long-term response to vasoactive therapy. Resp Med 2007, doi:10.1016/j.rmed.2007.05.020

6. Robbins IM, Gaine SP, Schilz R, Tapson VF, Loyd JE. Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus. Chest 2000;117:14-18.

7. Horn EM, Barst RJ, Poon M. Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus. Chest 2000;118:1229-1230.

8. Karmochkine M, Wechsler B, Godeau P, Brenot F, Jagot JL, Simmoneau G. Improvement of severe pulmonary hypertension in a patients with SLE. Ann Rheum Dis 1996;55:561-562.