Titre :

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

Auteur(s) :

Khanna, Dinesh [Auteur]
Kramer, Frank [Auteur]
Höfler, Josef [Auteur]
Ghadessi, Mercedeh [Auteur]
Sandner, Peter [Auteur]
Allanore, Yannick [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Denton, Christopher P. [Auteur]
Kuwana, Masataka [Auteur]
Matucci-Cerinic, Marco [Auteur]
Pope, Janet E. [Auteur]
Atsumi, Tatsuya [Auteur]
Bečvář, Radim [Auteur]
Czirják, Lászlo [Auteur]
De Langhe, Ellen [Auteur]
Hachulla, Eric [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Ishii, Tomonori [Auteur]
Ishikawa, Osamu [Auteur]
Johnson, Sindhu R. [Auteur]
Riccieri, Valeria [Auteur]
Schiopu, Elena [Auteur]
Silver, Richard M. [Auteur]
Smith, Vanessa [Auteur]
Stagnaro, Chiara [Auteur]
Steen, Virginia [Auteur]
Stevens, Wendy [Auteur]
Szücs, Gabriella [Auteur]
Truchetet, Marie-Elise [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Wosnitza, Melanie [Auteur]
Distler, Oliver [Auteur]

Titre de la revue :

Rheumatology

Nom court de la revue :

Rheumatology (Oxford)

Date de publication :

2024-03-09

ISSN :

1462-0332

Mot(s)-clé(s) en anglais :

biomarkers
diffuse cutaneous systemic sclerosis
riociguat
soluble guanylate cyclase stimulators

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Objective 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. Methods Patients ...
Lire la suite >Objective 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. Methods 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. Results By week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (P = 0.004 and P = 0.008, respectively). There were no differences in skin collagen markers between the two groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies was associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). Conclusion Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide–soluble guanylate cyclase–cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Date de dépôt :

2024-05-06T21:40:19Z
2024-08-27T15:17:30Z