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Original article
Effectiveness of four dynamic treatment strategies in patients with anticitrullinated protein antibody-negative rheumatoid arthritis: a randomised trial
  1. G Akdemir1,
  2. IM Markusse1,
  3. L Dirven1,
  4. N Riyazi2,
  5. GM Steup-Beekman3,
  6. PJSM Kerstens4,
  7. WF Lems4,5,
  8. TWJ Huizinga1 and
  9. CF Allaart1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Haga Hospital, The Hague, The Netherlands
  3. 3Department of Rheumatology, Bronovo Hospital, The Hague, The Netherlands
  4. 4Department of Rheumatology, Reade, Amsterdam, The Netherlands
  5. 5Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands
  1. Correspondence to Dr G Akdemir; g.akdemir{at}


Objective To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis.

Methods In the BeSt study, 184 ACPA-negative patients were randomised to: (1) sequential monotherapy, (2) step-up therapy, (3) initial combination including prednisone, (4) initial combination including infliximab. Treatment was targeted at the disease activity score (DAS) ≤2.4. Early response and 10-year outcomes were compared between the four strategy-arms in ACPA-negative patients.

Results ACPA-negative patients achieved more short-term functional improvement from initial combination therapy than when on monotherapy (at month 3, mean Health Assessment Questionnaire (HAQ) 0.71 vs 0.98, p=0.006; at month 6, 0.59 vs 0.87, p=0.004). Functional ability over time was comparable between the strategy-arms (p=0.551) with a mean HAQ of 0.6 at year 10 (p=0.580 for comparison across the strategy-arms). 10-year radiographic progression was negligible (median 0.5) and comparable between the 4 strategy-arms (p=0.082). At year 10, remission was achieved by 11/40 (28%), 9/45 (20%), 17/56 (30%) and 17/43 patients (40%) in strategy-arms 1–4, respectively (p=0.434). Over time, similar remission percentages were achieved in all strategy-arms (p=0.815). 18%, 16%, 20% and 21% in strategy-arms 1 to 4 (p=0.742) were in drug-free remission at year 10, with a median duration of 60 months across the arms.

Conclusions Initial combination therapy with methotrexate, sulfasalazine and prednisone, or methotrexate and infliximab, is the most effective treatment strategy for ACPA-negative patients, resulting in earlier functional improvement than when on initial methotrexate monotherapy. After 10 years of targeted treatment, in all strategy-arms favourable clinical outcomes were achieved and radiographic progression was limited.

Trial registration number NTR262, NTR265.

  • Rheumatoid Arthritis
  • Ant-CCP
  • Treatment

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