title: Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis.
abstract: BACKGROUND
  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).
  
  
  METHODS
  Data 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.
  
  
  RESULTS
  At 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.
  
  
  CONCLUSIONS
  Inflammatory 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.
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
authors.forename: Olivier
authors.initials: O
authors.lastname: Harari
authors.forename: Uwe
authors.initials: U
authors.lastname: Kobold
authors.forename: Janet S
authors.initials: JS
authors.lastname: Lee
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006242:Haptoglobins / Q000032:analysis / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D064451:Hepcidins / Q000097:blood / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D006242:Haptoglobins; D006454:Hemoglobins; D064451:Hepcidins; C508600:IL6 protein, human; D015850:Interleukin-6; C502936:tocilizumab