Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis

To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/ser...

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Published in:Rheumatology 2024-11, Vol.63 (11), p.3124-3134
Main Authors: Khanna, Dinesh, Kramer, Frank, Höfler, Josef, Ghadessi, Mercedeh, Sandner, Peter, Allanore, Yannick, Denton, Christopher P, Kuwana, Masataka, Matucci-Cerinic, Marco, Pope, Janet E, Atsumi, Tatsuya, Bečvář, Radim, Czirják, László, De Langhe, Ellen, Hachulla, Eric, Ishii, Tomonori, Ishikawa, Osamu, Johnson, Sindhu R, Riccieri, Valeria, Schiopu, Elena, Silver, Richard M, Smith, Vanessa, Stagnaro, Chiara, Steen, Virginia, Stevens, Wendy, Szücs, Gabriella, Truchetet, Marie-Elise, Wosnitza, Melanie, Distler, Oliver
Format: Article
Language:English
Subjects:
Adult
Biomarkers - blood
Biopsy
Clinical Science
Cyclic GMP - blood
Cyclic GMP - metabolism
Double-Blind Method
Female
Fibrosis - drug therapy
Humans
Life Sciences
Male
Middle Aged
Pyrazoles - therapeutic use
Pyrimidines - therapeutic use
Scleroderma, Diffuse - drug therapy
Scleroderma, Diffuse - pathology
Skin - drug effects
Skin - metabolism
Skin - pathology
Treatment Outcome
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Summary:To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. α-Smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. By week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P 
ISSN:1462-0324
1462-0332
1462-0332
1460-2172
DOI:10.1093/rheumatology/keae150