Background Hepcidin is an important link between inflammation and anemia in patients with rheumatoid arthritis (RA); hemoglobin itself is considered a negative acute phase measure in chronic inflammatory conditions like RA. However, the longitudinal association of hepcidin and hemoglobin with RA disease activity and acute phase remains to be explored.

Objectives We aimed to explore these associations in patients with RA.

Methods We consecutively included RA outpatients in a routine academic setting. Each patient was evaluated at baseline and 12 weeks thereafter using the clinical disease activity index (CDAI) and extensive peripheral blood tests, including serology, acute phase response (erythrocyte sedimentation rate, ESR; C reactive protein, CRP; and fibrinogen) and measures of iron metabolism (ferritin; transferrin; transferrin saturation, TS; hepcidin; and peripheral erythroid burst forming units, BFU-E). We analyzed baseline and week 12 values cross-sectionally in all patients; and change scores from baseline to week 12 in a subset of active patients with CDAI≥10 and a new DMARD initiation at baseline. We performed principal component analysis (PCA) to identify themes for all included variables. The strength of association of hepcidin and hemoglobin with the identified themes from the PCA was then analyzed.

Results Eighty-eight patients (68 females, 77%) were included (mean±SD age: 58±12 years; disease duration: 9.3±9.6 years). PCA identified four themes for all included parameters: clinical activity, acute phase, iron metabolism and hematopoiesis. At baseline and week 12 (steady state), both hepcidin and hemoglobin levels were ascribable primarily to the theme “iron metabolism”. Hemoglobin was also ascribable to “clinical activity” – to a similar extent as other acute phase parameters; but even more to the theme “acute phase”. Conversely, 12-week changes in hepcidin levels were ascribable to “changes in acute phase”, while changes in hemoglobin levels were ascribable to “changes in clinical activity” (Figure). In multivariable analysis CDAI changes were negatively, and BFU-E changes were positively, associated with hemoglobin changes (R²=0.615, p<0.05 for both); hepcidin changes were not associated with hemoglobin changes.

Figure: Loadings of hepcidin (solid lines) and hemoglobin (dotted lines) to the themes identified by principal component analysis, for baseline values (left), and for changes between baseline and week 12 (right)

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Conclusions In patients with RA, changes in hepcidin levels reflect changes in acute phase response, but not changes in clinical disease activity; changes in hemoglobin levels occur in conjunction with changes in clinical disease activity, but not with changes of the acute phase response. The association of clinical disease activity with hemoglobin seems to be stronger than its association with other acute phase parameters.

1. Song SN et al. Arthritis Res Ther. 2013;15:R141.

Disclosure of Interest None declared