Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study

Rheumatology (Oxford). 2016 Dec;55(12):2181-2190. doi: 10.1093/rheumatology/kew306. Epub 2016 Sep 16.

Abstract

Objectives: 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).

Conclusion: 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.

Trial registration: EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

Keywords: N-terminal pro-brain natriuretic peptide; cardiovascular risk; infliximab; insulin resistance; methotrexate; rheumatoid arthritis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aftercare
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / metabolism
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cholesterol, HDL / metabolism
  • Diabetes Complications / complications
  • Double-Blind Method
  • Early Diagnosis
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Infliximab / therapeutic use*
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Lipid Metabolism / drug effects
  • Male
  • Methotrexate / therapeutic use*
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Risk Factors
  • Surveys and Questionnaires
  • Treatment Outcome
  • Young Adult

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Glucocorticoids
  • Insulin
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Infliximab
  • Methylprednisolone
  • Methotrexate