M. M. S. SESSAREGO¹, M. M. R. RIZZI¹, M. M. G. Ghio¹, F. F. I. Indiveri^1
1Dept of internal medicine, D.I.MI University of Genoa, genova, Italy

Background: Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc), and it is difficult to treat.
Objectives: To asses the efficacy and tolerability of bosentan and the concomitant use of continuous iloprost in pulmonary hypertension secondary to systemic sclerosis (SSc-PAH
Methods: We have reclutated 8 patients all affected by SSc with increased PAH ( PA systolic pressure PAPS ≥ 45 mmHg by echocardiogram or PA pressure ≥ 35 mmHg at rest by cardiac catheterism), Word Health Organization (WHO) functional classes III-IV. We treated all the patients with bosentan (62,5 mg bid for 1 month and then 125 mg bid for 12 months), and with iloprost ( 0.5-2 ng/kg/min). For the unavailability of a periferical venous access, in all the patients a central venous catheter were positioned. This had permitted to administer Iloprost in a continuous (24h/24h) way, using a particular pump of infusion. All the patients were instructed for the use of the pump in order to be able to conduce the therapy at home. The Doppler echocardiogram, the six minute walking test (6MWT) and the complete pulmonary test were conduced at baseline and after three, six and twelve months.
Results: we observed an improvement in WHO functional class in 7 patients (functional class did no deteriorate in any patients); the PAPS value were improvement in all the patients and they were detectable since the first control; after three month of therapy the patients walked a mean of 25 m further in the 6MW test. The analysis of the functional pulmonary test showed an improvement in 3 of the 8 patient. All the subjects tolerated the therapy. No one discontinued therapy prematurely

Conclusion: Continuous IV infusion of iloprost associated with bosentan in SSc patients with PAPs improved symptoms of PAPs, hemodynamics and physical aspects of quality of life.
A possible synergy between the two drugs could be more efficacy than the use of the only bosentan for the treatment of pulmonary hypertension.
The oral dual endothelin receptors antagonist, bosentan, directly interferes with the pathogenic mechanism in systemic sclerosis and pulmonary hypertension, and it has been showed to possess antiproliferative and antifibrotics effects. Iloprost, at the moment considered a disease modifying drug for SSc, can reduce the production of endotelin-1 and stabilized the lung function.
The continuous infusion of iloprost allowed to obtained a longer pharmacological effects, and at the same time, to meliorate the daily routine because the patients were enable to conduce the infusion at home.

References: 1.Joglekar A, Tsai , McClosekey DA, Wilson JE, Seibold JR, Riley DJ. Bosentan in pulmonary arterial hypertension secondary to scleroderma. J Rheumatol 2006.3361-8
2.Scorza R, CaronniM, Mascagni B,et all. Effects of long-term cyclic iloprost therapy in sistemic sclerosis with Raynaud ‘s phemonenon. A randomized controlled study. Clin Exp Rheumatol 2001;19;509-8
3.Riemekasten G and Sunderkotter C :Vasoactive Therapies in systemic sclerosis Rheumatology 2006;45:49-51