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RMD Open. 2018 Mar 30;4(1):e000564. doi: 10.1136/rmdopen-2017-000564. eCollection 2018.

Conversion to seronegative status after abatacept treatment in patients with early and poor prognostic rheumatoid arthritis is associated with better radiographic outcomes and sustained remission: post hoc analysis of the AGREE study.

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Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Leeds Musculoskeletal Biomedical Research Unit, LTHT Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, France.
US Medical, Bristol-Myers Squibb, Princeton, New Jersey, USA.
Global Biometric Sciences, Bristol-Myers Squibb, Princeton, New Jersey, USA.



To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response.


Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at baseline and months 6 and 12 (double-blind phase). Conversion to seronegative status and its association with clinical response were assessed at months 6 and 12.


Abatacept plus MTX was associated with a greater decrease in ACPA (but not RF) titres and higher rates of both ACPA and RF conversion to seronegative status versus MTX alone. More patients converting to ACPA seronegative status receiving abatacept plus MTX achieved remission according to Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease Activity Index than patients who remained ACPA seropositive. Patients who converted to ACPA seronegative status treated with abatacept plus MTX had a greater probability of achieving sustained remission and less radiographic progression than MTX alone or patients who remained ACPA seropositive (either treatment).


Treatment with abatacept plus MTX was more likely to induce conversion to ACPA/RF seronegative status in patients with early, erosive RA. Conversion to ACPA seronegative status was associated with better clinical and radiographic outcomes.

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DMARD (biologic); ant-CCP; early rheumatoid arthritis; rheumatoid factor

Conflict of interest statement

Competing interests: PE: clinical trials and expert advice: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. JSS: expert advice and speakers’ bureau: Bristol-Myers Squibb; institutional grants: Phadia. RW: advisory board: Janssen; principal investigator: Galapagos; research grants: Roche; speakers’ bureau: Bristol-Myers Squibb. MLB: employee and shareholder: Bristol-Myers Squibb. SEC: employee and shareholder: Bristol-Myers Squibb. JY: employee and shareholder: Bristol-Myers Squibb. TWJH: the Department of Rheumatology at LUMC has received lecture fees/consultancy fees from Merck, UCB, Bristol-Myers Squibb, Biotest, Pfizer, GlaxoSmithKline, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takeda, Zydus, Epirus and Eli Lilly. DTSLJ and REMT: nothing to disclose.

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