CHICAGO – Early detection of incident systemic sclerosis–associated pulmonary arterial hypertension enhanced survival in a prospective cohort study of 131 patients from the multicenter PHAROS, according to data presented at the annual meeting of the American College of Rheumatology.
The survival rates for patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension who were enrolled in PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) "were better than for other recently described cohorts, with 1- and 3-year survival of 93% and 75%, respectively," said principal investigator Dr. Lorinda Chung of the department of immunology and rheumatology at Stanford (Calif.) University Medical Center.
"This may be due to the fact that we are screening our patients with [echocardiography and pulmonary function tests], and detecting their disease earlier, perhaps at a less severe stage," she said.
Furthermore, 17% of deaths in this cohort were not related to pulmonary arterial hypertension (PAH), suggesting that rheumatologists should remain involved in care even after patients are diagnosed with PAH, said Dr. Chung.
"Causes of death can be related to their underlying scleroderma or its complications," she said.
The independent predictors of death included functional class IV status, age greater than 60, male sex, and low (less than 39%) diffusion lung carbon monoxide, according to findings from a multivariate analysis.
PHAROS is a multicenter, U.S.-based prospective registry of SSc patients at high risk for PAH, or with definite pulmonary hypertension diagnosed by right heart catheterization within 6 months of enrollment. Of 434 patients enrolled in PHAROS, 131 had PAH.
Despite the availability of several therapies specific to pulmonary arterial hypertension, findings from recent studies of patients with incident scleroderma-associated PAH suggest that 1-year survival rates are as low as 72%-86% and 3-year survival rates are as low as 39%-67%.
This analysis included only patients with World Health Organization group I PAH, defined as mean pulmonary arterial pressure greater than 25 mm Hg and pulmonary capillary wedge pressure less than or equal to 15 mm Hg. Patients were excluded if they were found to have significant interstitial lung disease, defined as severe fibrosis on high-resolution CT or moderate fibrosis and a forced vital capacity less than 60% predicted.
Kaplan-Meier curves were used to estimate survival from the time of the diagnostic right heart catheterization, and Cox regression models were used to identify significant predictors of mortality.
The mean age of the 131 patients with PAH was 60.4±10.4 years, and most were female (84%) and white (82%). Fully 70% had limited cutaneous disease. Disease duration from the first Raynaud’s symptom was about 14.5 years and from the first non-Raynaud’s symptom was about 10 years.
"About a third of the patients had anticentromere antibodies and about a quarter had a nucleolar pattern on the ANA [antinuclear antibodies]," said Dr. Chung.
Over a mean follow-up period of 2.0 (1.4) years, 24 patients (18%) died. For the majority of those patients (20, or 83%), the cause of death was PAH or multiorgan failure, and the other four deaths were not related to PAH. In patients with incident SSc-associated PAH, 92.9 % survived at 1 year, 87.7 % at 2 years, and 74.8% at 3 years.
For the sake of comparison, Dr. Chung cited estimates from REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management), a U.S.-based prospective registry of patients with PAH, which includes a subgroup of patients with scleroderma. The majority of patients with incident SSc-associated PAH in the REVEAL registry were functional class III and IV at the time of PAH diagnosis, and their 3-year survival was only 54% – more than 20% less than patients in the PHAROS registry.
However, she said in the PHAROS cohort, "patients in functional class IV at enrollment had much poorer survival compared to those who were in functional classes I, II, or III." SSc-associated PAH patients with low diffusing capacity also had poorer survival. "The median value for the diffusion lung carbon monoxide was 39% predicted, and patients who had values below the median at enrollment experienced much poorer survival," she said.
Better survival was seen in systemic sclerosis–associated pulmonary arterial hypertension patients enrolled in the PHAROS registry.
PHAROS is an investigator-initiated study initially funded by Actelion, the Scleroderma Foundation, and the Sibley Foundation, with ongoing funding by Gilead. Dr. Chung reported financial relationships with Actelion, Gilead, Pfizer and United Therapeutics.