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

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

doi:10.1186/s13075-021-02573-0

Abstract

ObjectivesTo evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc).MethodsIn 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.ResultsNine 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.ConclusionsAnalysis 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 registrationClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

Highlights

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by vascular manifestations, immune dysfunction, and fibrosis involving multiple organs, especially the skin, lungs, gastrointestinal tract, and heart, which can lead to severe organ dysfunction [1]
A role for the innate immune system in the pathogenesis of SSc is increasingly recognized [10]. This is supported by studies showing that a subgroup of SSc patients displays activation of type I interferons (IFN), key regulators of the innate immune system in SSc patients [11,12,13,14], and an increased number of macrophages and monocytes in the blood and in the skin compared to healthy individuals [7, 15]
We report the outcome of an open-label clinical study in SSc patients treated with paquinimod (ClinicalTrials.gov Identifier: NCT01487551)

Summary

Introduction

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by vascular manifestations, immune dysfunction, and fibrosis involving multiple organs, especially the skin, lungs, gastrointestinal tract, and heart, which can lead to severe organ dysfunction [1]. A role for the innate immune system in the pathogenesis of SSc is increasingly recognized [10] This is supported by studies showing that a subgroup of SSc patients displays activation of type I interferons (IFN), key regulators of the innate immune system in SSc patients [11,12,13,14], and an increased number of macrophages and monocytes in the blood and in the skin compared to healthy individuals [7, 15].

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