Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis

Qureshi S, Adas M, Cope PJ, Mahfouz H, Bechman K, Deane KD, El-Gabalawy H, Emery P, Finckh A, Gilbert BTP, Holers VM, Isaacs JD, Kastbom A, Mankia K, Mikuls TR, Pratt AG, Rech J, Russell MD, Schett G, Trouw LA, Turesson C, Beers-Tas MH, Van Der Helm-Van Mil AH, Van Schaardenburg D, Van Steenbergen HW, Toes RE, Cope AP, Galloway J, Norton S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

RMD Open BMJ Publishing Group

Book Volume: 12

Article Number: e006368

Journal Issue: 1

DOI: 10.1136/rmdopen-2025-006368

Abstract

Background The aim of this systematic review and meta-analysis was to examine autoantibody positive individuals and define: (a) the relative risk of rheumatoid arthritis (RA) compared with autoantibody negative individuals and (b) the cumulative incidence of RA over time, in different populations. Methods A systematic literature search was performed in August 2025. Retrospective case control studies of individuals with RA and healthy matched controls were identified and relative risk of RA was calculated. Prospective observational studies or randomised controlled trials of autoantibody positive individuals were identified and pooled survival models were used to estimate cumulative incidence of progression to arthritis. Results 293 full-text articles fulfilled screening criteria and 26 were eligible for meta-analysis. The presence of serum autoantibodies confers between a 3.1 - 19.3-fold increase risk of developing RA. Prospective studies of anticyclic citrullinated peptide 2 (CCP2) or CCP3 positive individuals were grouped according to additional criteria; presence of arthralgia, presence/absence of immunoglobulin M rheumatoid factor (IgM-RF) and first-degree or second-degree relatives with RA. The estimated cumulative incidence of RA at 12 months was highest for CCP2 positive individuals with arthralgia and IgM-RF, at 35.2% (95% CI 29.3% to 41.2%). Conclusion A considerable number of autoantibodies have been examined as predictors for RA; however, the fastest rate of progression to RA in this study occurred in those with CCP2 and IgM-RF in combination with arthralgia. Importantly, the risk of developing RA changes over time for individuals with arthralgia, and they are at the highest risk of progression within the first 24 months of follow-up.

Authors with CRIS profile

Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

University of Amsterdam NL Netherlands (NL) Leiden University Medical Center NL Netherlands (NL) King’s College London GB United Kingdom (GB) University of Colorado Anschutz Medical Campus US United States (USA) (US) Newcastle University GB United Kingdom (GB) Lund University / Lunds universitet SE Sweden (SE) University of Manitoba CA Canada (CA) University of Leeds GB United Kingdom (GB) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) CH Switzerland (CH) Linköpings universitet / Linköping University SE Sweden (SE) University of Nebraska Medical Center (UNMC) US United States (USA) (US) Amsterdam Rheumatology & immunology Center (ARC) NL Netherlands (NL)

How to cite

APA:

Qureshi, S., Adas, M., Cope, P.J., Mahfouz, H., Bechman, K., Deane, K.D.,... Norton, S. (2026). Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis. RMD Open, 12(1). https://doi.org/10.1136/rmdopen-2025-006368

MLA:

Qureshi, Sumera, et al. "Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis." RMD Open 12.1 (2026).

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