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Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria
  1. Lena Bugge Nordberg1,
  2. Siri Lillegraven1,
  3. Elisabeth Lie1,
  4. Anna-Birgitte Aga1,
  5. Inge Christoffer Olsen1,
  6. Hilde Berner Hammer1,
  7. Till Uhlig1,
  8. Maria Karolina Jonsson1,2,
  9. Désirée van der Heijde1,3,
  10. Tore K Kvien1,
  11. Espen Andre Haavardsholm1
  12. and the ARCTIC working group
    1. 1Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
    2. 2Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
    3. 3Leiden University Medical Center, Leiden, Netherlands
    1. Correspondence to Dr Lena Bugge Nordberg, Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, Oslo N-0319, Norway; lenabuggenordberg{at}


    Objectives To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.

    Methods All patients had symptom duration from first swollen joint <2 years and were DMARD naïve with an indication for DMARD treatment. Patients were stratified as seropositive (positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF− and ACPA−), and disease characteristics were compared between groups.

    Results A total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, p<0.001) and tendons (median 3 vs 0, p<0.001), number of swollen joints (median 17 vs 8, p<0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups.

    Conclusions Seronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA.

    Trial registration number NCT01205854; Pre-results.

    • Rheumatoid Arthritis
    • Ant-CCP
    • Rheumatoid Factor
    • Early Rheumatoid Arthritis

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    • Handling editor Gerd R Burmester

    • Collaborators The ARCTIC working group: Hallvard Fremstad, Tor Magne Madland, Åse Stavland Lexberg, Hilde Haukeland, Erik Rødevand, Christian Høili, Hilde Stray, Anne Noraas Bendvold, Dag Magnar Soldal, Gunnstein Bakland.

    • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content and approved the final manuscript to be submitted and agreed to be accountable for all aspects of the work. Conception and design of the study: EAH, SL, LBN, A-BA, EL, ICO, HBH, TU, DvdH and TKK. Acquisition of data: EAH, A-BA, HBH, TU, JMK and the ARCTIC study group. Analysis and interpretation of data: LBN, ICO, EAH, SL, EL, A-BA, DvdH and TKK.

    • Funding The study has received grants from the Norwegian Research Council, the South-East Health Region in Norway, The Norwegian Rheumatism Association, the Norwegian Women's Public Health Association and unrestricted grant support from AbbVie, Pfizer, MSD, Roche and UCB.

    • Competing interests HBH has received speakers’s fees from BMS, UCB, Roche, Abbvie and Pfizer, v TKK has received grants from Abbvie, BMS, MSD/Schering-Plough, Pfizer/Wyeth, Roche, UCB and payment for lectures from Abbvie, Astra Zeneka, MSD/Schering-Plough, Pfizer/Wyeth, Roche, UCB, Celltrion and Eli Lily. EAH has received personal fees for consultancy, payment for lectures or development of educational material from UCB Pharma, Roche, Abbvie and Pfizer.

    • Ethics approval Local regional ethics committee.

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

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