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

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.