Journal Article

An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

Hesselstrand, Roger, Tuvesson, Helén, Riemekasten, Gabriela, Distler, Oliver, Sparre, Birgitta, Törngren, Marie, Nyhlén, Helén C., Distler, Jörg H. W., Wuttge, Dirk M., Andersson, Fredrik, Eriksson, Helena

2021

Overview

Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia ( n = 3) and headache ( n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551 . Registered on 7 September 2011

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Arthritis / Biological markers / Biomarkers / Biopsy / Care and treatment / Chemokines / Clinical Medicine / Clinical trial / Complications and side effects / Cytokines / Disease / Evaluation / Gene expression / Immune system / Interferon / Kinases / Klinisk medicin / Ligands / Mass spectrometry / Medical and Health Sciences / Medicin och hälsovetenskap / Medicine / Medicine & Public Health / Orthopedics / Paquinimod / Pathogenesis / Patient outcomes / Plasma / Proteins / Quinoline / Research Article / Rheumatology / Scientific imaging / Scleroderma / Scleroderma (Disease) / Skin fibrosis / Systemic scleroderma / Systemic sclerosis