A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

RMD Open. 2021 Sep;7(3):e001768. doi: 10.1136/rmdopen-2021-001768.

Abstract

Background: There is significant interest in determining risk factors in individuals at risk of rheumatoid arthritis (RA). A core set of risk factors for clinical arthritis development has not been defined.

Methods: A literature search and systematic literature review (SLR) was conducted to identify risk factors in individuals at risk of RA using Medline, Embase, PubMed and Central databases.

Results: 3854 articles were identified by the literature search. After screening of titles, 138 abstracts were reviewed and 96 articles finally included. Fifty-three articles included data on risk factors including autoantibodies, subclinical inflammation on imaging, clinical features, serum and cellular biomarkers and genetic markers. Risk factors were dependent on the at-risk population. There was good evidence for serum anticitrullinated protein antibodies (ACPA) levels, as risk factors for arthritis in all at-risk populations (n=13 articles). Subclinical inflammation on ultrasound (n=12) and MRI (n=6) was reported as a risk factor in multiple studies in at-risk individuals with musculoskeletal (MSK) symptoms and undifferentiated arthritis (UA). Clinical features were reported as a risk factor in at-risk individuals with MSK symptoms and UA (n=13). Other risk factors, including serum and cellular markers were less frequently reported.

Conclusions: Risk factors for arthritis development in RA are specific to the at-risk population. Serum ACPA confers risk in all populations; subclinical inflammation on imaging and clinical features confer risk in at-risk individuals with MSK symptoms. This SLR informed the EULAR taskforce for points to consider on conducting clinical trials and studies in individuals at risk of RA.

Keywords: arthritis; autoimmune diseases; autoimmunity; rheumatoid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Arthritis, Rheumatoid*
  • Autoantibodies
  • Biomarkers
  • Clinical Trials as Topic
  • Humans
  • Observational Studies as Topic
  • Risk Factors
  • Ultrasonography

Substances

  • Autoantibodies
  • Biomarkers