title: Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial.
abstract: OBJECTIVE
  To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA).
  
  
  METHODS
  Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression.
  
  
  RESULTS
  During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression.
  
  
  CONCLUSIONS
  The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA.
  
  
  BACKGROUND
  WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Department of Rheumatology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Kastbom
authors.affiliation: Section of Rheumatology, Department of Medicine, Helsingborg's lasarett, Helsingborg, Sweden Section of Rheumatology, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Forslind
authors.affiliation: Department of Learning, Informatics and Medical Education, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ernestam
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geborek
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
authors.forename: Johan A
authors.identifier: http://orcid.org/0000-0002-4915-2924
authors.initials: JA
authors.lastname: Karlsson
authors.affiliation: Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Ingemar F
authors.initials: IF
authors.lastname: Petersson
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Saedis
authors.initials: S
authors.lastname: Saevarsdottir
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Lundberg
mesh_terms: D000918:Antibody Specificity; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000187:drug effects; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000276:immunology; D011859:Radiography; D012460:Sulfasalazine / Q000627:therapeutic use; D013548:Sweden; D014746:Vimentin / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D005340:Fibrinogen; D000069285:Infliximab; D010751:Phosphopyruvate Hydratase; D008727:Methotrexate
keywords: Ant-CCP; Autoantibodies; DMARDs (biologic); DMARDs (synthetic); Early Rheumatoid Arthritis