Ivy Y Choi1, Danielle M Gerlag1, Marieke J Herenius1, Rogier M Thurlings1, Carla A Wijbrandts1, Dirk Foell2, Thomas Vogl3, Johannes Roth3, Paul P Tak4, Dirk Holzinger5. 1. Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. 2. Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany. 3. Institute of Immunology, University Hospital Muenster, Muenster, Germany. 4. Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands University of Cambridge, Cambridge, UK GlaxoSmithKline, Stevenage, UK. 5. Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany Institute of Immunology, University Hospital Muenster, Muenster, Germany.
Abstract
BACKGROUND: One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs. OBJECTIVE: To test the ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, to predict and monitor response to biologics in RA patients. METHODS: 170 RA patients treated with adalimumab (n=86), infliximab (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4 and 16 weeks after initiation of treatment and related to response outcome. RESULTS: Before initiation of treatment, responders showed significantly higher MRP8/14 protein complex levels compared with non-responders in each prospective cohort (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis showed that having high MRP8/14 baseline levels increased the odds of being a responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment, MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16 weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in non-responders. In patients treated with rituximab, MRP8/14 levels decreased by 59% after 16 weeks in responders and increased by 89% after 16 weeks in non-responders. CONCLUSION: Serum concentrations of MRP8/14 protein complex are a promising biomarker to predict response to biological therapy in active RA patients at baseline and could be used to monitor response to treatment across different mechanisms of action. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND: One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs. OBJECTIVE: To test the ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, to predict and monitor response to biologics in RApatients. METHODS: 170 RApatients treated with adalimumab (n=86), infliximab (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4 and 16 weeks after initiation of treatment and related to response outcome. RESULTS: Before initiation of treatment, responders showed significantly higher MRP8/14 protein complex levels compared with non-responders in each prospective cohort (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis showed that having high MRP8/14 baseline levels increased the odds of being a responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment, MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16 weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in non-responders. In patients treated with rituximab, MRP8/14 levels decreased by 59% after 16 weeks in responders and increased by 89% after 16 weeks in non-responders. CONCLUSION: Serum concentrations of MRP8/14 protein complex are a promising biomarker to predict response to biological therapy in active RApatients at baseline and could be used to monitor response to treatment across different mechanisms of action. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Carl Orr; Elsa Vieira-Sousa; David L Boyle; Maya H Buch; Christopher D Buckley; Juan D Cañete; Anca I Catrina; Ernest H S Choy; Paul Emery; Ursula Fearon; Andrew Filer; Danielle Gerlag; Frances Humby; John D Isaacs; Søren A Just; Bernard R Lauwerys; Benoit Le Goff; Antonio Manzo; Trudy McGarry; Iain B McInnes; Aurélie Najm; Constantino Pitzalis; Arthur Pratt; Malcolm Smith; Paul P Tak; Rogier Thurlings; João E Fonseca; Douglas J Veale; Sander W Tas Journal: Nat Rev Rheumatol Date: 2017-07-13 Impact factor: 20.543
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