title: MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ivy Y
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marieke J
authors.initials: MJ
authors.lastname: Herenius
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Thurlings
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Wijbrandts
authors.affiliation: Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.affiliation: Institute of Immunology, University Hospital Muenster, Muenster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Institute of Immunology, University Hospital Muenster, Muenster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands University of Cambridge, Cambridge, UK GlaxoSmithKline, Stevenage, UK.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany Institute of Immunology, University Hospital Muenster, Muenster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Holzinger
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood*; D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D040502:Calgranulin B / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D040502:Calgranulin B; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069285:Infliximab; D000068879:Adalimumab
keywords: Anti-TNF; Disease Activity; Rheumatoid Arthritis