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Open Access Highly Accessed Research article

ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial

Seth D Seegobin1, Margaret HY Ma2, Chanaka Dahanayake2, Andrew P Cope2, David L Scott3, Cathryn M Lewis1 and Ian C Scott12*

Author Affiliations

1 Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, Great Maze Pond, 8th Floor Tower Wing, London SE1 9RT, UK

2 Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, 1st Floor, New Hunt’s House, Guy’s Campus, King’s College London, Great Maze Pond, London SE1 1UL, UK

3 Department of Rheumatology, 3rd Floor, Weston Education Centre, King’s College Hospital, Cutcombe Road, London SE5 9RJ, UK

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Arthritis Research & Therapy 2014, 16:R13  doi:10.1186/ar4439

Published: 16 January 2014

Abstract

Introduction

UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used data from a randomized controlled trial - the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial - to examine whether responses to intensive combination treatments in early RA differ by ACPA status.

Methods

The CARDERA trial randomized 467 early active RA patients to receive: (1) methotrexate, (2) methotrexate/ciclosporin, (3) methotrexate/prednisolone or (4) methotrexate/ciclosporin/prednisolone in a factorial-design. Patients were assessed every six months for two years. In this analysis we evaluated 431 patients with available ACPA status. To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, disease activity scores on a 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), EuroQol, SF-36 physical component summary (PCS) and mental component summary (MCS) scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point using t-tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA.

Results

ACPA status influenced the need for combination treatments to reduce radiological progression. ACPA-positive patients had significant reductions in Larsen score progression with all treatments. ACPA-positive patients receiving triple therapy had the greatest benefits: two-year mean Larsen score increases comprised 3.66 (95% confidence interval (CI) 2.27 to 5.05) with triple therapy and 9.58 (95% CI 6.76 to 12.39) with monotherapy; OR for new erosions with triple therapy versus monotherapy was 0.32 (95% CI 0.14 to 0.72; P = 0.003). ACPA-negative patients had minimal radiological progression irrespective of treatment. Corticosteroid’s impact on improving DAS28/PCS scores was confined to ACPA-positive RA.

Conclusions

ACPA status influences the need for combination DMARDs and high-dose tapering corticosteroids in early RA. In CARDERA, combination therapy was only required to prevent radiological progression in ACPA-positive patients; corticosteroids only provided significant disease activity and physical health improvements in ACPA-positive disease. This suggests ACPA is an important biomarker for guiding treatment decisions in early RA.

Trial registration

Current Controlled Trials ISRCTN32484878