Session Type: Plenary Session II
Session Time: 11:00AM-12:30PM
Background/Purpose: Studies have shown that anti-citrullinated protein antibodies (ACPA) are a risk factor for the development of arthritis. We aimed to investigate in a prospective setting whether ACPA and other biomarkers could predict the development of ultrasound detected arthritis
Methods: Subjects with positive ACPA-test referred from primary-care to the Rheumatology clinic, that lacked arthritis in the hands, feet and any other symptomatic joints by clinical and ultrasound examination (according to EULAR-OMERACT definition), were recruited into the Risk-RA research program during 2015-2016, and were followed-up to the end of January 2019. at inclusion, a detailed clinical examination was performed and blood samples were analyzed for 13 specific ACPA reactivities (using custom made peptide microarray) as well as 92 inflammation-associated protein biomarkers (using a multiplex immunoassay with Olink proximity extension technology). Presence of HLA-SE was analyzed using DR low-resolution kit. Univariate and multivariate analysis were used to investigate the association between clinical and laboratory parameters and development of ultrasound detected arthritis adjusting for the follow-up time.
Results: 46% (30 out of 65) of the Risk RA subjects developed ultrasound detectable arthritis during a median follow-up time of 11 months. The remaining 54% (35 out of 55) were followed for a median of 27 months (range 17-39) without any signs of ultrasound detectable arthritis. Those subjects that developed arthritis had a higher prevalence of HLA-SE (83% vs 55%) as well as an increased incidence of ultrasound detected tenosynovitis (40% vs 5%) as compared to those that did-not develop arthritis. ACPA reactivities to citrullinated vimentim peptides (cit vim 2-17: 20% vs 6%; and cit vim 60-75: 67% vs 44%) and citrullinated histone peptides (cit H4 31-50: 87% vs 47%; and cit H3 21-44: 47% vs 22%) were a more common occurrence in subjects developing ultrasound detectable arthritis.
Backward selection in Cox regression model showed that ultrasound detectable arthritis could be predicted in a model including HLA-SE, tenosynovitis and ACPA reactivity to cit H4 31-50. Hazard ratio (HR) for arthritis development were 2.2 (95% CI 0.8-6, p=0.13) for HLA-SE carriers and 2.9 (95% CI 1.3-6.5, p=0.01) for tenosynovitis, and 3.4 (95% CI 1.2-10, p=0.02) for Anti-citrullinated H4 31-50 positivity. Only modest differences were observed for few of the tested inflammatory markers in those developing as compared to those not developing ultrasound detectable arthritis: Interleukin- 6 (3.9 vs 3.3 AU/ML), Programmed death-ligand 1 (4.9 vs 5.2 AU/ML) and Chemokine (C-X-C motif) ligand 6 (9.2 vs 9.5 AU/ML).
Conclusion: Certain ACPA fine specificities, HLA-SE and tenosynovitis predicts the development of ultrasound detectable arthritis in seropositive individuals with musculoskeletal symptoms who are at risk for RA.
To cite this abstract in AMA style:Hensvold A, Kisten Y, Circiumaru A, Hansson M, Sun M, Fei G, Vivar N, af Klint E, Rezaei H, Klareskog L, Antovic A, Catrina A. Development of Ultrasound Detectable Arthritis Among ACPA Positive Subjects with Musculoskeletal Symptoms: The Risk RA Prospective Study [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/development-of-ultrasound-detectable-arthritis-among-acpa-positive-subjects-with-musculoskeletal-symptoms-the-risk-ra-prospective-study/. Accessed September 30, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-of-ultrasound-detectable-arthritis-among-acpa-positive-subjects-with-musculoskeletal-symptoms-the-risk-ra-prospective-study/