Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Effect of the ETA Selective Endothelin Receptor Antagonist Ambrisentan on Digital Ulcers in Patients with Systemic Sclerosis: Results of a Prospective Pilot Study.
Chung1, Lorinda, Arefiev2, Kait, Yaqub2, Aaliya, Strahs2, Deborah, Lingala2, Bharathi, Fiorentino1, David
Previous studies have shown that the dual endothelin receptor antagonist (ETRA) bosentan is useful in the prevention of new digital ulcers (DU) in patients with systemic sclerosis (SSc), but has no effect on the healing of existing DU. We sought to evaluate the effect of the relatively ETA selective ETRA ambrisentan on the prevention and healing of DU.
This was a prospective open-label single-center study enrolling patients with limited or diffuse cutaneous SSc with at least one active DU located at or distal to the proximal interphalangeal joint. Patients with functional class III or IV pulmonary hypertension and those receiving phosphodiesterase-5 inhibitors, ETRAs, or prostacyclins within 4 weeks of screening were excluded. The primary endpoint was the difference in number of new DU that developed in the preceding 4 weeks after 24 weeks of therapy compared with baseline. Secondary endpoints included the % of patients who experienced complete healing of baseline DU; change in number and mean diameter of DU; change in physician global assessment of DU severity by visual analogue scale (VAS); and change in patient assessment of severity of DU and Raynaud's by VAS. A completers analysis was performed.
20 patients (80% female, mean age 49.3±13.8 years, 65% dcSSc) with a mean disease duration since first Raynaud symptom of 12.7±10.8 years were enrolled. 12 (60%) received stable doses of a calcium channel blocker and/or other vasodilator throughout the study. 16 patients completed 24 weeks of therapy. 2 withdrew due to lower extremity edema, 2 for scheduling conflicts. The mean number of new DU that developed 4 weeks prior to week 24 was not different from baseline (0.44±0.81 vs. 0.45±0.69). However, 14 (88%) patients had complete healing of all baseline DU at week 24. Of the 19 patients who completed 12 weeks of therapy, 7 (37%) had healed all baseline DU and 12 (63%) had healed at least 50% of baseline DU by week 12. The total number of DU decreased from 3.1±2.1 to 1.3±1.6 at week 24 (p=0.004) (Figure). For DU that did not heal, the mean diameter decreased from 3.3±1.6 mm to 1.6±1.5 mm (p<0.0001). Physician and patient assessments of DU severity were significantly improved at week 24 (p=0.015 for both), but patient assessment of Raynaud severity was not significantly different. The most common adverse events (AE) were lower extremity edema (50%), anemia (50%), and DU infection (40%). There were 3 serious AEs: 1 patient had a myocardial infarction and developed pulmonary edema; 1 patient was hospitalized for worsening of underlying SSc lung disease; and 1 patient had a severe Raynaud attack after an angiogram.
Ambrisentan may be useful in reducing ulcer burden and healing DU in SSc patients. A larger randomized double-blind placebo-controlled trial is warranted to further evaluate the efficacy of ambrisentan in the prevention and treatment of DU.
To cite this abstract, please use the following information:
Chung, Lorinda, Arefiev, Kait, Yaqub, Aaliya, Strahs, Deborah, Lingala, Bharathi, Fiorentino, David; Effect of the ETA Selective Endothelin Receptor Antagonist Ambrisentan on Digital Ulcers in Patients with Systemic Sclerosis: Results of a Prospective Pilot Study. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :668