Combination sequential therapy improves survival in SSc-related pulmonary arterial hypertension

Combination sequential therapy appears to be a beneficial alternative to monotherapy, leading to improved survival in patients with systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH), a study has shown.

The authors assessed all patients with SSc-associated PAH from the Spanish Scleroderma Registry and split them into three groups: monotherapy vs sequential combination vs upfront combination therapy. Death from any cause at 1, 3 and 5 years from PAH diagnosis was the primary endpoint.

Of the 1,817 patients identified, 76 (4.2 percent) had SSc-related PAH. Of those with SSc-related PAH, 34 (45 percent) received monotherapy (endothelin receptor antagonist: n=22; 29 percent; phosphodiesterase-5 inhibitors: n=12; 16 percent), 25 (33 percent) sequential combination and 17 (22 percent) upfront combination therapy.

At baseline, patients in the sequential combination group had a lower forced vital capacity/diffusing capacity for carbon monoxide compared with those from other treatment groups (2.9±1.1 vs 1.8±0.4 vs 2.3±0.8; p=0.085). The combination groups also had a higher mean pulmonary arterial pressure (37.2±8.7 vs 40.8±8.8 vs 46±15.9 mm Hg; p=0.026).

Treatment regimen (p=0.017) and functional class (p=0.007) were independently associated with mortality. Sequential combination therapy conferred a protective effect against mortality (hazard ratio [HR], 0.11, 95 percent confidence interval [CI], 0.03–0.51; p=0.004), while upfront combination therapy showed a protective trend (HR, 0.68, 95 percent CI, 0.23–1.97; p=0.476).

Survival from PAH diagnosis among monotherapy, sequential and upfront combination groups was 78 percent, 95.9 percent and 94.1 percent at 1 year; 40.7 percent, 81.5 percent and 51.8 percent at 3 years; and 31.6 percent, 56.5 percent and 34.5 percent at 5 years (p=0.007), respectively. No significant between-group difference was seen for side effects.