Anti-citrullinated protein antibody profiles predict changes in disease activity in patients with rheumatoid arthritis initiating biologics

Abstract

Objectives To determine whether an expanded antigen-specific ACPA profile predicts changes in disease activity in patients with RA initiating biologics. Methods The study included participants from a prospective, non-randomized, observational RA cohort. For this sub-study, treatment groups of interest included biologic-naïve initiating anti-TNF, biologic-exposed initiating non-TNF, and biologic-naïve initiating abatacept. ACPAs to 25 citrullinated peptides were measured using banked enrolment serum. Principal component analysis (PCA) was performed and associations of resulting principal component (PC) scores (in quartiles) and anti-CCP3 antibody (≤15, 16–250 or >250 U/ml) with EULAR (good/moderate/none) treatment response at 6 months were examined using adjusted ordinal regression models. Results Participants (n = 1092) had a mean age of 57 (13) years and 79% were women. At 6 months, 68.5% achieved a moderate/good EULAR response. There were three PCs that cumulatively explained 70% of variation in ACPA values. In models including the three components and anti-CCP3 antibody category, only PC1 and PC2 were associated with treatment response. The highest quartile for PC1 (odds ratio [OR] 1.76; 95% CI: 1.22, 2.53) and for PC2 (OR 1.74; 95% CI: 1.23, 2.46) were associated with treatment response after multivariable adjustment. There was no evidence of interaction between PCs and treatment group in EULAR responses (P-value for interaction >0.1). Conclusion An expanded ACPA profile appears to be more strongly associated with biologic treatment response in RA than commercially available anti-CCP3 antibody levels. However, further enhancements to PCA will be needed to effectively prioritize between different biologics available for the treatment of RA.

Novel insights into the management of rheumatoid arthritis: one year in review 2024

“…In a recent prospective observational study, Aripova and colleagues investigated the predictive role of an expanded antigen-specific ACPA profile compared to the commercially available anti-cyclic citrullinated peptide (CCP)-3 assay in 1092 patients with RA initiating bDMARDs. Two out the three expanded ACPA profiles, identified by a principal component analysis and explaining -~ 70% of the variability in ACPA expression, demonstrated a significant superiority to predict positive treatment response to bDMARDs compared to conventional anti-CCP-3 assay (29). The impact of the expanded antigen specific ACPA profile was independent of the mechanism of action of the bDMARD.…”