PMID- 29787569 OWN - NLM STAT- MEDLINE DCOM- 20180731 LR - 20181114 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 5 DP - 2018 TI - Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study. PG - e0197001 LID - 10.1371/journal.pone.0197001 [doi] LID - e0197001 AB - INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (rho = 0.57, P = 0.03), CDUS (rho = 0.53, P = 0.04) and bone marrow oedema (rho = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit. CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects. FAU - Andersen, Martin AU - Andersen M AUID- ORCID: 0000-0002-6852-9985 AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. AD - Translational Immunology, Biopharmaceutical Research Unit, Malov, Novo Nordisk, Denmark. FAU - Boesen, Mikael AU - Boesen M AD - Department of Radiology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Ellegaard, Karen AU - Ellegaard K AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Soderstrom, Kalle AU - Soderstrom K AD - Translational Immunology, Biopharmaceutical Research Unit, Malov, Novo Nordisk, Denmark. FAU - Soe, Niels H AU - Soe NH AD - Department of Orthopaedics, Section of Hand Surgery, Gentofte University Hospital, Hellerup, Denmark. FAU - Spee, Pieter AU - Spee P AD - Translational Immunology, Biopharmaceutical Research Unit, Malov, Novo Nordisk, Denmark. FAU - Morch, Ulrik G W AU - Morch UGW AD - Biomarkers, Novo Nordisk, Soborg, Denmark. FAU - Torp-Pedersen, Soren AU - Torp-Pedersen S AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Bartels, Else M AU - Bartels EM AUID- ORCID: 0000-0001-9302-9678 AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Danneskiold-Samsoe, Bente AU - Danneskiold-Samsoe B AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Karlsson, Lars AU - Karlsson L AD - Translational Immunology, Biopharmaceutical Research Unit, Malov, Novo Nordisk, Denmark. FAU - Bliddal, Henning AU - Bliddal H AD - The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180522 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antirheumatic Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) SB - IM MH - Adult MH - Aged MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/diagnostic imaging/*drug therapy/metabolism/*pathology MH - Case-Control Studies MH - Chemokine CCL2/metabolism MH - Female MH - Humans MH - Image Processing, Computer-Assisted/*methods MH - In Vitro Techniques MH - Interleukin-6/*analysis/metabolism MH - Male MH - Middle Aged MH - Pilot Projects MH - Prognosis MH - Synovial Membrane/diagnostic imaging/drug effects/metabolism/*pathology MH - Tissue Culture Techniques MH - Ultrasonography, Doppler, Color/methods PMC - PMC5963776 COIS- We have the following interests: This study was supported in part by Novo Nordisk. During the course of this study Martin Andersen, Kalle Soderstom, Pieter Spee, Ulrik GW Morch, and Lars Karlsson were employed at Novo Nordisk. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2018/05/23 06:00 MHDA- 2018/08/01 06:00 PMCR- 2018/05/22 CRDT- 2018/05/23 06:00 PHST- 2018/02/05 00:00 [received] PHST- 2018/04/24 00:00 [accepted] PHST- 2018/05/23 06:00 [entrez] PHST- 2018/05/23 06:00 [pubmed] PHST- 2018/08/01 06:00 [medline] PHST- 2018/05/22 00:00 [pmc-release] AID - PONE-D-18-03920 [pii] AID - 10.1371/journal.pone.0197001 [doi] PST - epublish SO - PLoS One. 2018 May 22;13(5):e0197001. doi: 10.1371/journal.pone.0197001. eCollection 2018.