THU0257 Acpa-Negative RA Patients Benefit from Initial Combination Therapy with Early Clinical Improvement - A Sub-Analysis of the Best Study
Authors: G. Akdemir, I. Markusse, L. Dirven, M. van den Broek, E. Molenaar, A. Schouffoer, P. Kerstens, W. Lems, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-citrullinated protein antibodies (ACPA)-positive (+) and ACPA-negative (−) rheumatoid arthritis (RA) patients may have different disease outcomes and may require different therapies. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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&lt;0.001) and HAQ (1.3±0.7, p=0.024) in ACPA+ patients. Both ACPA− and ACPA+ patients achieved DAS≤2.4 (p&lt;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&lt;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&lt;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. <h3>Conclusions</h3> 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. <h3>Disclosure of Interest</h3> : 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. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2142