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The window of opportunity in ACPA-positive rheumatoid arthritis is not explained by ACPA characteristics
  1. Annemiek Willemze1,
  2. Michael P M van der Linden1,
  3. Saskia le Cessie2,
  4. Leendert A Trouw1,
  5. Rene E M Toes1,
  6. Tom W J Huizinga1,
  7. Annette H M van der Helm-van Mil1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Clinical Epidemiology and Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Annemiek Willemze, Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; a.willemze{at}

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Very early therapy of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs is associated with lower levels of joint destruction and a higher chance of achieving remission.1,,5 Having symptoms for >12 weeks at treatment initiation is a strong and independent risk factor for a persistent disease course.1 3,,5 These observations have led to the concept of the 'window of opportunity'.2 This hypothesis presumes that underlying disease processes are not fully matured in the very early stage of arthritis, making modulation more successful. However, putative biological mechanisms remain unexplored.

Anti-citrullinated protein antibodies (ACPA) precede arthritis development and are associated with a severe disease course.6 We hypothesised that the ACPA response broadens within the very early phase of RA and in doing so limits the 'window of opportunity'. Therefore, it was examined whether patients who were assessed within 12 weeks of symptom onset had a less broadened ACPA response than patients with longer symptom duration.

Three hundred and nine ACPA-positive patients (defined by anti-CCP2 positivity) fulfilling the 1987 ACR criteria for …

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  • Funding This study was supported by grants from the Centre for Medical Systems Biology (CMSB) and Netherlands proteomics platform within the framework of the Netherlands Genomics Initiative (NGI); by the European Union (Sixth Framework Programme integrated project Autocure and Seventh Framework Programme integrated project Masterswitch). The work of AHMvdHvM is supported by a grant of the Netherlands Organisation of Health Research and Development. The work of AW is supported by the Dutch Organization for Scientific Research (AGIKO grant). LAT work is supported by an NWO-ZonMW VENI grant. REMT's work is supported by a NWO-ZonMW VIDI and VICI grant from the Dutch Organization for Scientific Research.

  • Ethics approval This study was conducted with the approval of the Ethics committee of the Leiden University Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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