Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic sclerosis (SSc) is characterized by progressive impairment of the microvascular system and decrease of peripheral blood perfusion (PBP) (1-3). The vasoactive peptide endothelin-1 (ET-1) seems to be implicated in these events (4). Laser Doppler flowmetry (LDF) is a technique to evaluate blood perfusion at peripheral sites, such as the central area of the fingertips (2). The aim of this study was to investigate long-term effects of ET-1 receptor antagonism on PBP evaluated by LDF technique in SSc patients.
Methods: Twenty-six SSc patients (mean age 62±12SD years, mean SSc duration 8±4 years) were enrolled during their programmed standard treatment protocols for digital ischaemia. At baseline (T0), 13 patients already receiving cyclic intravenous infusion of iloprost (average 80 mcg/day, for 5 continuous days, every three months), continued the treatment for further 3 years (ILO group: T1,T2,T3). The remaining 13 patients, although they continued the same cyclic intravenous iloprost treatment as the previous group, also received bosentan 125 mg twice a day for 3 years (ILO+BOS group: T1,T2,T3) since complaining digital ulcers. PBP was yearly evaluated in all SSc patients using LDF at both basal temperature and after heating of the LDF probe at 36°C to test microvascular dilation capacity. PBP was measured at the central area of the fingertips of the 2nd to 5thfinger bilaterally, scoring the average value as perfusion units (PU) (2). Non-parametric tests were used for the statistical analysis.
Results: A progressive and statistically significant increase of PBP was observed in the ILO+BOS group at basal temperature during the follow-up (median PU T0 51, T1 74, T2 70, T3 85, respectively, p=0.007); at 36°C, PBP significantly increased only during the first two years of follow-up (median PU T0 81, T1 104, T2 110, respectively, p=0.0003; T3 105). In contrast, not statistically significant PBP changes were observed in ILO group at both basal temperature (median PU T0 104, T1 78, T2 55, T3 44, p=0.70) and 36°C (median PU T0 126, T1 108, T2 109, T3 87, p=0.45). Gradient of PU between the evaluations at basal temperature and at 36°C was found progressively decreased during the followup in the ILO group, but not in the ILO+BOS group. Two SSc patients experienced new digital ulcers in the ILO+BOS group (15%), and four in the ILO group (31%). No serious side effects were observed. Transient increase of liver transaminases was managed by temporary discontinuation of bosentan treatment in two cases.
Conclusion: Long-term treatment with ET-1 receptor antagonist in combination with iloprost was found to significantly increase PBP in SSc patients, in contrast to the treatment with iloprost alone. This seems in agreement with the recent observation that long-term bosentan treatment reduces microvascular damage progression, as assessed by naifold capillaroscopy (5).
References: 1. Cutolo M, et al. Nat Rev Rheumatol 2010; 6, 578-87. 2. Cutolo M, et al. J Rheumatol 2010; 37:1174-80. 3. Rosato E, et al. J Rheumatol 2010; 37: 2531-9. 4. Vancheeswaran R, et al. J Rheumatol 1994; 21:1838-44. 5. Cutolo M et al. J Rheumatol. 2013;40:40-5.
Actelion Pharmaceuticals US,
Actelion Pharmaceuticals US,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-treatment-with-endothelin-receptor-antagonist-increases-peripheral-blood-perfusion-in-systemic-sclerosis-patients/