Abstract
IntroductionOur objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA).MethodsData of patients receiving tocilizumab or placebo in the MEASURE study were analysed. We investigated associations at baseline and during tocilizumab treatment among haemoglobin, parameters of haemoglobin and iron homeostasis [ferritin, total iron-binding capacity (TIBC), hepcidin, haptoglobin], IL-6 and acute-phase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] to identify statistical correlates of rise in haemoglobin level.ResultsAt baseline, CRP and haptoglobin were inversely correlated (modestly) with haemoglobin levels. After treatment with tocilizumab, CRP, hepcidin, ferritin and haptoglobin levels fell alongside increases in TIBC and haemoglobin. The falls in CRP, hepcidin and haptoglobin levels in the first 2 weeks correlated with a week 12 rise in TIBC and haemoglobin.ConclusionsInflammatory anaemia improves in patients with RA treated with tocilizumab. This improvement correlates with the degree of suppression of systemic inflammation, reduction in hepcidin and haptoglobin and increase in iron-binding capacity. These clinical data provide evidence of a role for IL-6 signalling in the inflammatory anaemia of RA.
Highlights
Our objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers in patients with rheumatoid arthritis (RA)
One patient assigned to placebo received tocilizumab from study start and was evaluated in the tocilizumab group for the current analysis
Mean age was slightly higher in this study than in the tocilizumab phase 3 pivotal trials; disease characteristics were similar [11,12,13,14,15]
Summary
Our objective was to determine the interrelationships of interleukin (IL)-6 receptor inhibition with haemoglobin, acute-phase reactants and iron metabolism markers (including hepcidin) in patients with rheumatoid arthritis (RA). One of the mechanisms of the inflammatory response is the sequestration of iron in macrophages, leading to decreased availability of iron to invading pathogens. Chronic inflammatory diseases—including Castleman’s disease [1], systemic-onset juvenile idiopathic arthritis [2] and rheumatoid arthritis (RA) [3]—are often accompanied by anaemia. Tocilizumab reduces hepcidin levels and improves anaemia in patients with Castleman’s disease [1] and in an animal model of arthritis [10]. Tocilizumab treatment is associated with increased haemoglobin levels in patients with RA [11,12,13,14,15]. The current analysis tested associations between changes in haematological parameters and acute-phase markers in a phase 3B clinical trial of coefficient was complemented with the non-parametric tocilizumab in RA (MEASURE) [16,17]
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