Changes in Hepcidin and Hemoglobin After Anti-TNF-alpha Therapy in Children and Adolescents With Crohn Disease

Abstract

Objectives: Anemia is the most common systemic complication of inflammatory bowel disease, is more common in affected children than in adults, and is mediated in large part by chronic inflammation. Inflammation increases levels of the iron-regulatory protein hepcidin, which have been elevated in adults with Crohn disease.

Methods: We measured serum hepcidin-25 and hemoglobin (Hgb) in 40 children and adolescents with Crohn disease at baseline and 10 weeks after initiation of anti-tumor necrosis factor (TNF)-α therapy. Measures of disease activity, inflammatory markers, and cytokines were obtained in all subjects. Anemia was defined by World Health Organization criteria.

Results: At baseline hepcidin and C-reactive protein levels were correlated, and 95% of subjects were anemic. After anti-TNF-α therapy, median (interquartile range) hepcidin concentrations decreased significantly and the distribution narrowed (27.9 [16.2, 52.9] vs 23.2 [11.1, 37.7] ng/mL, P = 0.01). Mean (standard deviation) Hgb also increased significantly (10.6 ± 1.2 to 10.9 ± 1.1 g/dL, P = 0.02), and the increase was sustained at 12 months, although 90% of participants continued to meet anemia criteria at 10 weeks. Disease activity and markers of inflammation also decreased and albumin levels increased. In generalized estimating equation analyses, higher TNF-α, interleukin 6, erythrocyte sedimentation rate, and C-reactive protein were associated with higher hepcidin concentrations (P = 0.04, P = 0.03, P = 0.003, and P < 0.001, respectively), and increased levels of disease activity were associated with higher hepcidin.

Conclusions: In children with Crohn disease, anti-TNF-α therapy is associated with decreased levels of hepcidin and increased Hgb 10 weeks after induction. Improvement in anemia may be a secondary benefit for children who receive this therapy.