Sildenafil, Bosentan Combination vs Sildenafil Monotherapy in SSc-Associated PAH
Both sildenafil and bosentan were well tolerated and had similar rates of adverse events.
In patients with systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH), there was no significant difference in the efficacy of initial combination therapy with sildenafil and bosentan vs sildenafil monotherapy, according to research presented at the European League Against Rheumatism (EULAR) Congress, held in Amsterdam, June 13 to 16, 2018.
In this single-center, double-blind, prospective, randomized, placebo-controlled trial (ClinicalTrials.gov identifier: NCT03053739), researchers randomly assigned 34 patients with SSc-PAH in a 1:1 ratio to sildenafil (20 mg 3 times daily) and placebo or to the combination of sildenafil and bosentan (62.5 mg twice daily for 4 weeks maximum, up to 125 mg twice daily) for 24 weeks.
SSc-PAH was defined as pulmonary artery systolic pressure (PASP) >35 mm Hg and New York Heart Association functional class II and III with forced vital capacity >60%.
The primary end point was to analyze the change in PA pressures from baseline to 24 weeks, as measured by echocardiography. Changes in the 6-minute walk distance, time to clinical worsening, and adverse events at 24 weeks served as the secondary end points.
Participants who were randomly assigned to monotherapy experienced a mean change of −1.0 mm Hg in PASP compared with ±2.1 mm Hg in the combination therapy group (P =.56). In the monotherapy group, the mean survival time was 23.76±0.59 weeks, and in the combination group, it was 23.28±0.23 weeks, with a hazard ratio of 0.73 (95% CI, 0.04-11.7; P =.87).
The mean change in 6-minute walk distance was 15.88±31.83 m in the monotherapy group vs 25.88±38.25 m in the combination group (P =.38), and the "satisfactory clinical response" was 82.3% in the combination group vs 70% in the monotherapy group (odds ratio, 1.9; 95% CI, 0.38-9.88; P =.44).
Both medications were well tolerated and had similar adverse event rates in both groups.
The researchers concluded that the initial combination therapy of sildenafil and bosentan prevented further deterioration in patients, but larger studies may be necessary to confirm these findings.
Dwivedi P, Sharma SK, Dhir V, Rohit MK, Behera D, Jain S. A randomized double blind placebo controlled trial to compare the efficacy of initial combination therapy vs monotherapy for pulmonary arterial hypertension in systemic sclerosis. Presented at: European League Against Rheumatism (EULAR) Congress 2018; June 13-16, 2018; Amsterdam, The Netherlands. Abstract AB0797.