PMID- 34330322 OWN - NLM STAT- MEDLINE DCOM- 20210813 LR - 20210813 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 23 IP - 1 DP - 2021 Jul 31 TI - An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod. PG - 204 LID - 10.1186/s13075-021-02573-0 [doi] LID - 204 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. CI - (c) 2021. The Author(s). FAU - Hesselstrand, Roger AU - Hesselstrand R AD - Department of Rheumatology, Skane University Hospital and Lund University, Lund, Sweden. roger.hesselstrand@med.lu.se. FAU - Distler, Jorg H W AU - Distler JHW AD - University of Erlangen-Nuremberg, Erlangen, Germany. FAU - Riemekasten, Gabriela AU - Riemekasten G AD - Universitatsklinikum Lubeck, Lubeck, Germany. FAU - Wuttge, Dirk M AU - Wuttge DM AD - Department of Rheumatology, Skane University Hospital and Lund University, Lund, Sweden. FAU - Torngren, Marie AU - Torngren M AD - Active Biotech AB, Lund, Sweden. FAU - Nyhlen, Helen C AU - Nyhlen HC AD - Active Biotech AB, Lund, Sweden. FAU - Andersson, Fredrik AU - Andersson F AD - Active Biotech AB, Lund, Sweden. FAU - Eriksson, Helena AU - Eriksson H AUID- ORCID: 0000-0001-9899-7600 AD - Active Biotech AB, Lund, Sweden. FAU - Sparre, Birgitta AU - Sparre B AD - Active Biotech AB, Lund, Sweden. FAU - Tuvesson, Helen AU - Tuvesson H AD - Active Biotech AB, Lund, Sweden. FAU - Distler, Oliver AU - Distler O AD - Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. LA - eng SI - ClinicalTrials.gov/NCT01487551 PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210731 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Biomarkers) RN - 0 (Quinolines) RN - HB76GLG27V (paquinimod) SB - IM MH - Biomarkers MH - Humans MH - Quality of Life MH - *Quinolines/adverse effects MH - *Scleroderma, Systemic/drug therapy MH - Treatment Outcome PMC - PMC8325221 OTO - NOTNLM OT - Clinical trial OT - Paquinimod OT - Skin fibrosis OT - Systemic sclerosis COIS- 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. GR and DMW declare that they have no competing interests. MT, HT, and HE are employees and stock owners of Active Biotech AB. HCN is a former employee at Active Biotech AB and owns stocks in Active Biotech AB. FA and BS are former employees at Active Biotech AB. 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). EDAT- 2021/08/01 06:00 MHDA- 2021/08/14 06:00 PMCR- 2021/07/31 CRDT- 2021/07/31 06:16 PHST- 2020/08/12 00:00 [received] PHST- 2021/07/06 00:00 [accepted] PHST- 2021/07/31 06:16 [entrez] PHST- 2021/08/01 06:00 [pubmed] PHST- 2021/08/14 06:00 [medline] PHST- 2021/07/31 00:00 [pmc-release] AID - 10.1186/s13075-021-02573-0 [pii] AID - 2573 [pii] AID - 10.1186/s13075-021-02573-0 [doi] PST - epublish SO - Arthritis Res Ther. 2021 Jul 31;23(1):204. doi: 10.1186/s13075-021-02573-0.