title: Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis.
abstract: BACKGROUND
  The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFα) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment.
  
  
  METHODS
  This prospective work investigated the number of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNFα treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control.
  
  
  RESULTS
  Non-responder patients with RA show an increased number of monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNFα treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders.
  
  
  CONCLUSIONS
  The absolute number of circulating monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.
authors: Luis
authors: L
authors: Chara
authors: Ana
authors: A
authors: Sánchez-Atrio
authors: Ana
authors: A
authors: Pérez
authors: Eduardo
authors: E
authors: Cuende
authors: Fernando
authors: F
authors: Albarrán
authors: Ana
authors: A
authors: Turrión
authors: Julio
authors: J
authors: Chevarria
authors: Miguel A
authors: MA
authors: Sánchez
authors: Jorge
authors: J
authors: Monserrat
authors: Antonio
authors: A
authors: de la Hera
authors: Alfredo
authors: A
authors: Prieto
authors: Ignacio
authors: I
authors: Sanz
authors: David
authors: D
authors: Diaz
authors: Melchor
authors: M
authors: Alvarez-Mon
mesh_terms: D000068879:Adalimumab; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D008727:Methotrexate