Concomitant PAH may up mortality risk in systemic sclerosis

The presence of pulmonary arterial hypertension (PAH) in individuals with systemic sclerosis is associated with an increased mortality risk, a study from Singapore showed.

Using the Systemic Sclerosis Cohort Singapore (SCORE), the researchers identified 490 patients (mean age at diagnosis of systemic sclerosis, 47.6 years, 87 percent female, 73 percent Chinese) with systemic sclerosis of whom 50 patients had PAH, 92 had interstitial lung disease (ILD), and 43 had concomitant ILD-pulmonary hypertension (PH). The 93 patients with PAH or ILD-PH were diagnosed based on echocardiography (systolic pulmonary artery pressure [PAP] ≥50 mm Hg; n=56) or right heart catheterization (mean PAP ≥25 mm Hg; n=37). ILD was diagnosed using high-resolution computed tomography, with severity based on pulmonary function test.

Time between diagnosis of systemic sclerosis and pulmonary involvement varied significantly, with a mean 3.2, 4.4, and 6.8 years to ILD, ILD-PH, and PAH diagnosis, respectively (p=0.026).

Five-year survival rates from time of systemic sclerosis diagnosis were lowest in patients with ILD-PH (77 percent), followed by those with PAH (88 percent), ILD (90 percent), and no/mild pulmonary involvement (93 percent). This translated to an increased mortality risk in patients with systemic sclerosis who also had concomitant ILD-PH (hazard ratio [HR], 3.77, 95 percent confidence interval [CI], 2.05–6.93; p<0.001), followed by those with PAH (HR, 3.03, 95 percent CI, 1.60–5.76; p<0.001) and those with ILD (HR, 1.84, 95 percent CI, 1.04–3.28; p=0.037) compared with patients with no/mild pulmonary involvement, in univariate analysis. [Semin Arthritis Rheum 2019;doi:10.1016/j.semarthrit.2019.11.005]

However, after adjusting for confounders*, only PAH was independently associated with an elevated mortality risk in patients with systemic sclerosis (adjHR, 2.39, 95 percent CI, 1.13–5.07; p=0.023), with no apparent association between ILD (adjHR, 0.61; p=0.240) or ILD-PH (adjHR, 0.94; p=0.881) and increased mortality.

Other factors associated with elevated mortality risk were male gender (adjHR, 3.02; p=0.002), age at systemic sclerosis diagnosis (adjHR, 1.06; p<0.001), malabsorption (adjHR, 2.59; p=0.001), digital ulcer or gangrene (adjHR, 2.09; p=0.007), and forced vital capacity (FVC; adjHR, 0.97; p<0.001).

“[E]arly aggressive treatment with PAH targeted therapies might have contributed to improved outcomes of ILD-PH,” suggested the researchers. Additionally, the association of FVC with increased mortality suggests that ILD severity may have a greater part to play in mortality risk than merely ILD presence, they said.

Factors associated with an increased risk of hospitalization were renal crisis (β**, 0.30; p=0.004), right heart failure (β, 0.36; p<0.001), and PAH medications*** (β, 0.22; p=0.003). However, the risk of hospitalizations did not significantly differ between those with PAH, ILD, or ILD-PH and those with no/mild pulmonary involvement (p=0.136). 

According to the researchers, with the potential role of ethnicity in the clinical features of systemic sclerosis, the use of the SCORE cohort may enable generalization of the findings to other populations, namely Asian ones. 

“Future research should focus on better characterization of systemic sclerosis patients with ILD-PH and on development of better treatment strategies in this group of patients,” they said. In addition, the identification of factors that increase the risk of hospitalization or mortality could help physicians “identify patients who require closer monitoring and early treatment,” they noted.