Background Bosentan (Tracleer®) reduces the number of new digital ulcers (DU) in subjects with systemic sclerosis (SSc) and ongoing digital ulcer disease (Korn at all 2004, Matucci et al. 2011). Bosentan also improves skin perfusion of hands in SSc patients with pulmonary arterial hypertension (Rosato et al 2010). Whether SSc patients without PAH have the same benefit remains to be established.
Objectives The objective of the HOME study was to evaluate the effect of 12 weeks of bosentan treatment on the blood flow in the hands of SSc patients with a clinically relevant reduction of blood flow in the hands, compared to healthy controls, as measured by laser Doppler imaging.
Methods HOME was a national, multicenter, phase 4, randomized clinical trial. The blood flow in both hands was measured with the PeriScan PIM 3a laser Doppler (Perimed, Sweden) in 52 healthy controls and in 56 bosentan naive SSc patients, suffering from DU in the previous 2 years. The hand was divided into 3 separate regions: ROI1, distal to the PIP joint of the 3 middle fingers; ROI2, distal to the metacarpal joints and proximal to the PIP joint and ROI 3, the hand proximal to the metacarpal joints. Patients with a 50% reduced blood flow in ROI1 compared to mean blood flow in healthy controls were included in the study and were treated with bosentan twice daily for 12 consecutive weeks. The data was evaluated on an intention-to-treat basis. MEC approval was obtained for all sites. The trial was registered in clinicaltrials.gov (NCT01395732).
Results 18 patients had more than 50% blood flow reduction in ROI1. Two patients refused treatment, so 16 patients were treated with bosentan (4 males, age 49±11 (mean ±stdev)). Three patients stopped the treatment after 5, 8 and 11 weeks (one adverse event and two reasons unrelated to bosentan treatment). In 1 patient with increased ALAT/ASAT, after up-titration, the dose was reduced to 62.5mg. The blood flow in the hand significantly increased from 34.2±10.1 (mean±stdev) before treatment to 42.4±15.4 and 46.5±19.8 at 4 and 12 weeks respectively (p=0.064 and p=0.027, paired sampled t-test). This increase was most profound in ROI1 and absent in ROI3.
Conclusions Bosentan significantly increases the blood flow in the hands of SSc patients with a history of DU in the 2 previous years and a more than 50% reduction of blood flow in the hands compared to healthy controls.
Rosato et al. J. Rheumatol 2010; 37(12): 2531-9
Korn JH et all. Arthritis Rheum 2004; 50: 3985-93.
Matucci et al. Annals Rheum Dis 2011;70:32-8.
Disclosure of Interest H. Knaapen: None Declared, A. Voskuyl: None Declared, P. van Daele: None Declared, J. Bloemsaat-Minekus Employee of: Actelion PharmaceuticalsNederland B.V., M. Vonk: None Declared, A. Schuerwegh: None Declared