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

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

doi:10.1186/s13075-021-02573-0

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

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

^*Corresponding author for this work

Clinic of Rheumatology

34 Citations (Scopus)

Abstract

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.

Original language	English
Article number	204
Journal	Arthritis Research and Therapy
Volume	23
Issue number	1
ISSN	1478-6354
DOIs	https://doi.org/10.1186/s13075-021-02573-0
Publication status	Published - 12.2021

Funding

RH received funding from Active Biotech AB related to the study. JHWD has consultancy relationships with Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi, and UCB. JHWD has received research funding from Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, and UCB. JHWD is a stock owner of 4D Science. OD has/had consultancy relationship and/or has received research funding from Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Drug Development International Ltd., CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, Glenmark Pharmaceuticals, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target BioScience, and UCB in the area of potential treatments of scleroderma and its complications. He has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143). The study was funded by the sponsor Active Biotech AB.

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Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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Hesselstrand, R., Distler, J. H. W., Riemekasten, G., Wuttge, D. M., Törngren, M., Nyhlén, H. C., Andersson, F., Eriksson, H., Sparre, B., Tuvesson, H., & Distler, O. (2021). An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod. Arthritis Research and Therapy, 23(1), Article 204. https://doi.org/10.1186/s13075-021-02573-0

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

abstract = "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.",

author = "Roger Hesselstrand and Distler, \{J{\"o}rg H.W.\} and Gabriela Riemekasten and Wuttge, \{Dirk M.\} and Marie T{\"o}rngren and Nyhl{\'e}n, \{Hel{\'e}n C.\} and Fredrik Andersson and Helena Eriksson and Birgitta Sparre and Hel{\'e}n Tuvesson and Oliver Distler",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

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doi = "10.1186/s13075-021-02573-0",

language = "English",

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T1 - An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

AU - Hesselstrand, Roger

AU - Distler, Jörg H.W.

AU - Riemekasten, Gabriela

AU - Wuttge, Dirk M.

AU - Törngren, Marie

AU - Nyhlén, Helén C.

AU - Andersson, Fredrik

AU - Eriksson, Helena

AU - Sparre, Birgitta

AU - Tuvesson, Helén

AU - Distler, Oliver

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85111709972

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DO - 10.1186/s13075-021-02573-0

M3 - Journal articles

C2 - 34330322

AN - SCOPUS:85111709972

SN - 1478-6354

VL - 23

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 204

ER -

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

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