title: Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.
abstract: OBJECTIVE
  To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies.
  
  
  METHODS
  Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values.
  
  
  RESULTS
  Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007).
  
  
  CONCLUSIONS
  When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX.
  
  
  BACKGROUND
  EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Lesley-Anne
authors.initials: LA
authors.lastname: Bissell
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Elizabeth M A
authors.initials: EM
authors.lastname: Hensor
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.|Faculty of Pharmacy, Wroclaw Medical University, Wroclaw.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kozera
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Mackie
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Agata N
authors.initials: AN
authors.lastname: Burska
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Nam
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Keen
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Edith
authors.initials: E
authors.lastname: Villeneuve
authors.affiliation: Department of Biochemical Diagnostics, Medical University of Lublin, Lublin, Poland.
authors.forename: Helena
authors.initials: H
authors.lastname: Donica
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Andrews
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds & NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK, a.w.morgan@leeds.ac.uk.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000359:Aftercare; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology; D008076:Cholesterol, HDL / Q000378:metabolism; D048909:Diabetes Complications / Q000150:complications; D004311:Double-Blind Method; D042241:Early Diagnosis; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005938:Glucocorticoids; D007328:Insulin; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000069285:Infliximab; D008775:Methylprednisolone; D008727:Methotrexate
keywords: N-terminal pro-brain natriuretic peptide; cardiovascular risk; infliximab; insulin resistance; methotrexate; rheumatoid arthritis