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THU0257 Acpa-Negative RA Patients Benefit from Initial Combination Therapy with Early Clinical Improvement - A Sub-Analysis of the Best Study
  1. G. Akdemir1,
  2. I. Markusse1,
  3. L. Dirven1,
  4. M. van den Broek1,
  5. E. Molenaar2,
  6. A. Schouffoer3,
  7. P. Kerstens4,
  8. W. Lems5,
  9. T. Huizinga1,
  10. C. Allaart1
  1. 1Rheumatology, LUMC, Leiden
  2. 2Rheumatology, Groene Hart Hospital, Gouda
  3. 3Rheumatology, Haga Hospital, the Hague
  4. 4Rheumatology, Reade
  5. 5Rheumatology, VUMC, Amsterdam, Netherlands


Background Anti-citrullinated protein antibodies (ACPA)-positive (+) and ACPA-negative (−) rheumatoid arthritis (RA) patients may have different disease outcomes and may require different therapies.

Objectives To determine which treatment strategy in Disease Activity Score (DAS) steered treatment for ACPA− RA patients is better in the BeSt study and evaluate whether there is a difference in outcomes in ACPA− and ACPA+ patients.

Methods 184 ACPA− and 300 ACPA+ patients with active early RA were randomized to: 1 sequential monotherapy; 2 step-up therapy; 3 initial combination with prednisone; 4 initial combination with infliximab. Treatment adjustments were made every 3 months targeted at low disease activity (DAS≤2.4).

DAS response, functional ability (health assessment questionnaire; HAQ), radiographic joint damage progression (Sharp/vanderHeijde Score; SHS), (drug-free) remission percentages and toxicity over 10 years were compared between the 4 treatment strategies in ACPA− patients and between ACPA− and ACPA+ patients.

Results Baseline DAS (mean ± SD 4.6±0.9) and HAQ (1.5±0.7) in ACPA− patients were higher than DAS (4.3±0.8, p<0.001) and HAQ (1.3±0.7, p=0.024) in ACPA+ patients. Both ACPA− and ACPA+ patients achieved DAS≤2.4 (p<0.001) and HAQ improvement earlier on initial combination therapy (arms 3 and 4) than on initial MTX monotherapy (arms 1 and 2). Failure on initial MTX monotherapy and subsequent failure on the 2nd and 3rd treatment steps in arms 1 and 2 were similar for ACPA− and ACPA+ patients. After 3 months of initial combination therapy in arm 3 a DAS≤2.4 was achieved in 55% of ACPA− patients and 65% of ACPA+ patients (in arm 4 in 42% and 53%, respectively). Remission occurred earlier in arms 3 and 4 than in arms 1 and 2, with similar percentages in ACPA− and ACPA+ patients. Drug-free remission after ten years was achieved by 27% of ACPA− patients and 6% of ACPA+ patients (p<0.001) with a median duration of 69 and 32 months, respectively, without significant differences between treatment arms for ACPA− patients. After 10 years SHS progression in ACPA− patients was not different between the 4 arms, but there was more SHS progression in ACPA+ patients (median (IQR) 4.5 (1.0-13.5)) than in ACPA− patients (0.5 (0.0-3.0), p<0.001). During ten years similar numbers of adverse events (AE) and serious AE were reported in ACPA− and ACPA+ patients, without significant differences between treatment arms.

Conclusions ACPA− patients achieved earlier DAS (low disease activity and remission) response and functional improvement on initial combination therapy than on initial monotherapy, as did ACPA+ patients. With subsequent DAS steered treatment, clinical response was similar in ACPA− and ACPA+ patients, without differences between treatment arms, but after 10 years, radiographic damage progression was significantly higher in ACPA+ patients and ACPA− patients had achieved more often and more sustained drug-free remission than ACPA+ patients.

Disclosure of Interest : G. Akdemir: None declared, I. Markusse: None declared, L. Dirven: None declared, M. van den Broek: None declared, E. Molenaar: None declared, A. Schouffoer: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, C. Allaart Grant/research support: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.

DOI 10.1136/annrheumdis-2014-eular.2142

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