Quality Control worksheet

Aditya A. Joshi, Ryan Davey, Youlan Rao, Kai Shen, Raymond L. Benza, Amresh Raina

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Pulmonary arterial hypertension (PAH) is a result of changes in the distal pulmonary vasculature that can lead to progressive debilitating symptoms and often result in death. While smooth muscle cell proliferation, endothelial dysfunction, and vascular inflammation are all believed to play important roles in PAH, but recently, more attention has been focused on inflammation mechanisms. Emerging evidence suggests that there may be circulating factors that can serve as biomarkers to monitor disease progression and treatment response. This study used patients enrolled in two clinical trials that were treated with treprostinil (TRUST-1 and FREEDOM-C2). Plasma was collected at baseline and at 12 or 16 week follow up and analyzed using DiscoveryMAP at Myriad RBM.

Parameter Patients alive (n=200) Patients who died (n=6) P Value
Angiopoietin-1 (ng/mL) 5.9 (1.3-53) 22.3 (7.6-30.5) 0.001
Angiopoietin-2 (ng/mL) 8.7 (1.8-52) 8.2 (2.1-81.1) 0.81
Basic fibroblast growth factor (pg/mL) 10.5 (3.2-115) 14.3 (3.9-48.1) 0.03
Interleukin-1 beta (pg/mL) 1.6 (1.6-38.5) 5.0 (5.0-6.9) <0.001
Interleukin-6 (pg/mL) 2.2 (2.2-173) 5.0 (5.0-5.0) <0.001
Interleukin-8 (pg/mL) 8.7 (2.1-1293) 5.0 (5.0-367) <0.68
Interleukin-13 (pg/mL) 4.6 (4.6-1207) 156 (156-156) <0.001
Vascular endothelial growth factor (pg/mL) 56 (11.5-1934) 160 (15.7-753) <0.03
Matrix metalloproteinase-9 (ng/mL) 85.5 (11-1550) 635 (195-901) <0.001

The above table is an example of just one stratified analysis the authors’ conducted correlating a set of baseline hemodynamic and inflammatory proteins with study outcome. The data presented demonstrated that for patients who died at the end of the study correlated with higher levels of circulating inflammatory proteins. These increases in inflammation markers were also associated with hospitalizations. The authors concluded that that these biomarkers may have clinical and subclinical implications in assessing treatment response and future outcomes in PAH patients. Myriad RBM’s DiscoverMAP technology can assist in biomarker identification in patients for a variety of assessments, including treatment response and patient outcome.