Trial reportArthritis research & therapy2014
ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial.
Trial report in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Sex bias consideration in healthcare machine-learning research: a systematic review in rheumatoid arthritis.BMJ open · 2025Pooled it
- Early-life animal and farming exposures and the risk of rheumatoid arthritis: findings from the E3N French cohort study.RMD open · 2025Trial
- Disease activity and treatment response in early rheumatoid arthritis: an exploratory metabolomic profiling in the NORD-STAR cohort.Arthritis research & therapy · 2025Trial
- Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies.Arthritis research & therapy · 2020Trial
- Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?The Journal of rheumatology · 2015Trial
- The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis.Psychosomatic medicineTrial
- Real-world effectiveness of tofacitinib in monotherapy or in combination with csDMARDs in patients with rheumatoid arthritis: A collaboration between Dutch registries (TOFADUDAP study).Clinical rheumatology · 2026Article
- Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis.Immunological reviews · 2026Review
- Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- First-line tumor necrosis factor inhibitor versus abatacept treatment choice in real-world patients with anticitrullinated protein antibody- and rheumatoid factor-positive rheumatoid arthritis.Journal of comparative effectiveness research · 2026Article
- Impact of Seropositivity on Mortality and Extra-Articular Manifestations in Rheumatoid Arthritis: A Nationwide Propensity-Matched Cohort Study.Mediterranean journal of rheumatology · 2025Article
- Article
- The Inflammatory Link of Rheumatoid Arthritis and Thrombosis: Pathogenic Molecular Circuits and Treatment Approaches.Current issues in molecular biology · 2025Review
- Integrative multi-omic profiling in blood reveals distinct immune and metabolic signatures between ACPA-negative and ACPA-positive rheumatoid arthritis.Frontiers in immunology · 2025Article
- Article
- Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis.Doklady. Biochemistry and biophysics · 2024Article
- Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.ACS pharmacology & translational science · 2024Review
- The Role of Citrullination Modification in CD4Biomolecules · 2024Review
- Noncoding RNAs in rheumatoid arthritis: modulators of the NF-κB signaling pathway and therapeutic implications.Frontiers in immunology · 2024Review
- Upregulation of interferon-γ response genes in monocytes and T cells identified by single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionUK 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.
methodsThe 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.
resultsACPA 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.
conclusionsACPA 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 registrationCurrent Controlled Trials ISRCTN32484878.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.