Effects of treatment with etanercept versus methotrexate on sleep quality, fatigue and selected immune parameters in patients with active rheumatoid arthritis

Clin Exp Rheumatol. 2016 Sep-Oct;34(5):848-856. Epub 2016 Jun 22.


Objectives: To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX).

Methods: Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16.

Results: BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group.

Conclusions: Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology
  • Disability Evaluation
  • Drug Therapy, Combination
  • Etanercept / adverse effects
  • Etanercept / therapeutic use*
  • Fatigue / immunology
  • Fatigue / physiopathology
  • Fatigue / prevention & control*
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Patient Reported Outcome Measures
  • Pilot Projects
  • Polysomnography
  • Predictive Value of Tests
  • Prospective Studies
  • Remission Induction
  • Sleep / drug effects*
  • Sleep Wake Disorders / immunology
  • Sleep Wake Disorders / physiopathology
  • Sleep Wake Disorders / prevention & control*
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antirheumatic Agents
  • Etanercept
  • Methotrexate