Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients

Author: L. Rice, Cristina M. Padilla, S. McLaughlin, A. Mathes, J. Ziemek, S. Goummih, S. Nakerakanti, M. York, G. Farina, M. Whitfield, R. Spiera, R. Christmann, J. Gordon, J. Weinberg, R. Simms, and R. Lafyatis
Date Published: June-2015
Source: Journal of Clinical Investigation

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β–regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β–regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS).