title: Changes in anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes serum levels in patients with rheumatoid arthritis following treatment with different biological drugs.
abstract: OBJECTIVE
  Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis (RA), and also have a prognostic value for more aggressive disease. Whether anti-CCP levels may change during treatment according to clinical response is matter of debate. Likewise, it is unknown whether different biological drugs have peculiar effects on anti-CCP levels. This study aimed to investigate changes in anti-CCP serum levels in RA patients on biological drugs with different mechanism of action.
  
  
  METHODS
  We studied 71 patients with active RA tested positive for anti-CCP who started a first biological drug (54 anti-TNF-α drug, 9 rituximab, 8 tocilizumab). In 14 patients stopping anti-TNF-α treatment for ineffectiveness, rituximab was started. Anti-CCP and rheumatoid factor (RF) isotypes (IgM, IgA, IgG) levels were measured at entry, 12 months and again at 12 months after swapping to rituximab.
  
  
  RESULTS
  After 1 year of therapy of the first biological drug, patients taking anti-TNF-α drugs showed a significant reduction of the anti-CCP levels (p=0.002), and all RF isotypes (p=0.003). Also patients treated with rituximab or tolicizumab had a significant decrease in anti-CCP (p=0.01) and RF isotype levels (p=0.01). Anti-CCP levels did not correlated with DAS28 over time. In patients switching to rituximab after failure of TNF-α blockers, anti-CCP levels did not change at 12 months (p=0.06), despite of the reduction of DAS28 (p=0.02) and RFs levels (p=0.02).
  
  
  CONCLUSIONS
  Our study showed that anti-CCP levels may change during RA course, regardless of the biological drug used and the clinical response.
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy. florenzo.iannone@uniba.it.
authors.forename: Florenzo
authors.initials: F
authors.lastname: Iannone
authors.affiliation: Patologia Clinica, A.O. Universitaria Consorziale Policlinico, Bari, Italy.
authors.forename: Marilina
authors.initials: M
authors.lastname: Tampoia
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Giannini
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lopalco
authors.affiliation: Department of Rheumatology, Policlinico Le Scotte, University of Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.affiliation: Allergologia e Immunologia Clinica, A.O. S. Maria degli Angeli, Pordenone, Italy.
authors.forename: C Danilo
authors.initials: CD
authors.lastname: Villalta
authors.affiliation: Department of Rheumatology, Policlinico Le Scotte, University of Siena, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D062072:Patient Acuity; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood*; D000069283:Rituximab / Q000008:administration & dosage / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007155:Immunologic Factors; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D000069283:Rituximab; D012217:Rheumatoid Factor; C502936:tocilizumab