Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial

Arthritis Care Res (Hoboken). 2018 Jun;70(6):861-868. doi: 10.1002/acr.23427. Epub 2018 Apr 25.


Objective: To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA).

Methods: Post hoc analyses were performed in patients from the PREMIER trial with early RA undergoing 2 years of adalimumab (ADA), methotrexate (MTX), or ADA + MTX combination therapy. Low disease activity was defined as a score <3.2 on the 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP), and clinical response by the American College of Rheumatology criteria for 20% improvement at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex-specific World Health Organization criteria, were analyzed in mixed-effects models for longitudinal data in men and women as predictors of progressive joint damage, as measured by the modified total Sharp/van der Heijde score (ΔSHS). Data were adjusted for treatment and other patient characteristics, including the DAS28-CRP.

Results: Baseline hemoglobin was inversely associated with ΔSHS in adjusted analyses (P < 0.05 for both sexes). Baseline anemia predicted greater ΔSHS in MTX-treated patients over 104 weeks, and in ADA- and combination-treated patients over 26 weeks. Lower hemoglobin concentrations over time, as well as time with anemia, were associated with greater damage progression (P < 0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity.

Conclusion: Low hemoglobin is a DAS28-CRP-independent predictor of radiographic joint damage progression in MTX-treated patients with early RA. This effect decreases over time in ADA- and combination-treated patients, and in clinical responders irrespective of treatment modality.

Trial registration: ClinicalTrials.gov NCT00195663.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / drug therapy
  • Disease Progression
  • Female
  • Hemoglobins / metabolism*
  • Humans
  • Joints / diagnostic imaging
  • Male
  • Methotrexate / therapeutic use
  • Radiography


  • Antirheumatic Agents
  • Hemoglobins
  • Adalimumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00195663