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Clinical Trial
. 2023 Sep:254:109695.
doi: 10.1016/j.clim.2023.109695. Epub 2023 Jul 20.

Biomarkers of fibrosis, inflammation, and extracellular matrix in the phase 3 trial of tocilizumab in systemic sclerosis

X Rebecca Sheng  1 , Xia Gao  2 , Courtney Schiffman  2 , Jenny Jiang  2 , Thirumalai R Ramalingam  2 , Celia J F Lin  2 , Dinesh Khanna  3 , Margaret Neighbors  4
Affiliations
Free article
Clinical Trial

Biomarkers of fibrosis, inflammation, and extracellular matrix in the phase 3 trial of tocilizumab in systemic sclerosis

X Rebecca Sheng et al. Clin Immunol. 2023 Sep.
Free article

Abstract

Drug development for systemic sclerosis (SSc) benefits from understanding the relationship between disease and circulating biomarkers to enable activities such as patient stratification and evaluation of therapeutic response. We measured biomarkers in serum from SSc patients from a phase 3 trial of tocilizumab (focuSSced) and compared baseline levels with healthy controls (HCs). Several baseline biomarkers appeared elevated in SSc patients compared to HCs, suggesting activation of epithelial damage, inflammation, fibrosis, and extracellular matrix (ECM) remodeling. Baseline correlations among both periostin/COMP and ECM biomarker subsets implicated their participation in fibroblast activation. Tocilizumab treatment modulated serum biomarkers of macrophage activation, inflammation, and ECM turnover, including collagen formation and degradation neoepitopes. Baseline CRP, periostin, and SP-D showed prognostic trends for worsening lung function, and IL-6, COMP, periostin, and Pro-C3 showed prognostic trends for worsening skin thickness. These prognostic results warrant confirmation in additional patient cohorts to verify their utility.

Keywords: Biomarkers; Fibrosis; IL-6; Systemic sclerosis; Tocilizumab.

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Conflict of interest statement

Declaration of Competing Interest All authors, except for DK, were employees of Genentech, Inc., a member of the Roche group, at the time this work was performed and own/owned Roche stock and/or options. DK is a consultant to Astra Zeneca, Boehringer Ingelheim, BMS, Genentech/ Roche, Chemomab, Horizon, Prometheus, Merck, and Mitsubishi. TRR is currently an independent consultant, and CJFL is currently an employee of Vera Therapeutics, CA.

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