PoM No 6, 2014

Publication of the Month


June 06/14: ACPA status’ influence on therapy response in RA


Key messages:

  • ACPA status influences the need for and benefits of combination DMARDS and high-dose tapering corticosteroids in rheumatoid
  • ACPA is an important biomarker for guiding treatment decisions in early rheumatoid arthritis


Seegobin SD, Ma MHY, Dahanayake C, Cope AP, Scott DL, Lewis CM, Scott IC
ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and coticosteroids: secondary analysis of a randomized controlled trial
Arthritis Res Ther. 2014,16: R13


Background: Although the presence of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients has been recognised as indicating a worse prognosis with higher rates of erosive damage than for ACPA negative patients, there has been little data on how or if ACPA status affects responses to therapy. This study aimed to examine if combination disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroid have different effects on radiological progression, disease activity, disability and quality of life in ACPA-positive and ACPA-negative patients.

Summary: The Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial randomized 467 patients with early active RA to one of four treatment arms: methotrexate alone (1), methotrexate with ciclosporine (2) or with prednisolone (3), and triple therapy with methotrexate, ciclosprin and prednisolone (4). Outcomes at 24 months were assessed and analysed against the results for ACPA testing on baseline archived sera for the 431 individual for whom such samples were available.

Conclusions: The findings of this study show strong evidence that ACPA-positive patients benefit from intensive combination therapy and that monotherapy with methotrexate resulted in considerable worsening of radiological damage. There was no evidence that combination treatments improve disease outcomes beyond methotrexate monotherapy in ACPA negative patients. ACPA-negative patients had minimal radiological progression irrespective of treatment. High dose corticosteroids had significant beneficial effects on ACPA positive patients but made no significant difference to ACPA-negative patients.

Comment: The usefulness of determining ACPA status as a prognostic indicator has become more accepted and this data suggests a further benefit in terms of suggesting treatment regime and limiting the use of potentially harmful medications to those patients who will gain maximum advantage from them.


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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.