Progression to Inflammatory Arthritis Associated With Autoantibody Positivity in First-Degree Relatives With RA

Autoantibody positive screening in a nonclinical setting can identify rheumatoid arthritis (RA)-related autoantibody positivity, as well as autoantibodies associated with a higher risk for inflammatory arthritis (IA), according to study results published in Annals of the Rheumatic Diseases.

The Studies of the Etiology of RA (SERA) is a prospective study designed to identify environmental and genetic risk factors for RA; SERA enrolls individuals at increased risk for RA from rheumatology clinics across the United States.

For the current study, individuals with first-degree relatives with RA were included in the analyses. At study entry, participants received screening for RA-related biomarkers, including anti-anticyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF). Patients who were tested autoantibody positive at baseline and positive at follow-up were classified as autoantibody-positive persistent. Patients who were tested positive at baseline but negative at follow-up were considered autoantibody-positive nonpersistent.

The primary outcome was development of IA during follow-up, defined as the presence of at least 1 swollen joint consistent with RA-like synovitis. Logistic regression was performed to assess the effect of autoantibody positivity persistence on risk for progression to IA. Cox proportional hazard models were used to determine the 5-year risk for incident IA based on baseline screening factors. Models were adjusted for other known RA risk factors, including race/ethnicity, the presence of shared epitope alleles, smoking status, C-reactive protein levels, and self-reported tender or stiff joints at baseline.

The study cohort included 131 patients (mean age, 47.7±15.0 years; 77.9% women; 79.4% non-Hispanic White) who tested positive for autoantibodies at baseline, did not have IA, and had at least 1 follow-up visit. The majority of patients (64.1%) remained autoantibody positive at follow-up and were classified as autoantibody-positive persistent. Over a median follow-up of 4.4 years, 20 study participants (15.3%) developed IA.

Individuals who had baseline anti-CCP levels greater than vs less than 2x the standard cutoff level were significantly more likely to develop IA (odds ratio [OR], 13.37; 95% CI, 3.03-59.06; P =.001). In total, 32% and 26% of participants who had baseline anti-CCP levels greater than 2x the standard and optimal cutoffs, respectively, developed IA within 5 years of baseline. In Cox proportional hazard models, both anti-CCP+ greater than 2x the standard cutoff (hazard ratio [HR], 4.09; 95% CI, 1.67-10.04) and optimal cutoff at screening (HR, 3.95; 95% CI, 1.57-9.91) were significantly associated with 5-year risk for incident IA.

Overall, these data support the use of autoantibody screening to identify patients at particularly high risk for incident IA. Elevated anti-CCP antibodies were predictive of later IA development, though RF did not appear to influence incident arthritis risk.

One of the study limitations included the fact that the small sample size limited the generalizability.

“Monitoring for the development of IA in [autoantibody positive] individuals and similar [autoantibody] testing approaches in at-risk populations may identify candidates for prevention studies in RA,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Bemis EA, Demoruelle MK, Seifert JA, et al. Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting. Published online September 14, 2020. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217066