Radiographic progression of rheumatoid arthritis (RA) is higher in patients with triple positivity for antimodified protein antibodies (AMPAs) compared with patients with anticitrullinated peptide antibodies (ACPAs) alone or AMPA negativity, according to study results published in The Lancet Rheumatology.

ACPAs have widely been used in the diagnosis of RA and prediction of radiographic progression; however, little is known about the role of other antibodies against proteins and peptides that have been post-translationally modified by carbamylation and acetylation.

In the current study, the researchers aimed to evaluate the effect of combinations of AMPAs on radiographic progression in patients with new-onset RA.


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Demographic, clinical, laboratory, and radiographic data were collected from patients enrolled in the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank. Patients included in the current study had RA and at least 1 swollen joint; were free of blood-borne virus infections; started receiving methotrexate treatment within 6 weeks of their baseline visit; and attended a clinical assessment at 12 months. The AMPAs were measured at baseline using an enzyme-linked immunosorbent assay, and radiographs were scored using the Sharp-van der Heijde (SvH) method, which is the sum of the total erosion and total joint space narrowing scores.

Researchers measured AMPA profiles in 362 (67% women) of the 1073 patients enrolled in the SERA study between March 2011 and April 2015. They identified 4 major groupings of autoantibodies to post-translationally modified peptides: single positivity for ACPAs (n=73; 20%), double positivity for ACPAs and antiacetylated peptide antibodies (AAPAs; n=45; 12%); triple positivity for ACPAs, AAPAs, and anticarbamylated peptide antibodies (n=151; 42%); and AMPA-negative (n=74; 20%).

Researchers compared the radiographic progression of RA between the 4 groups using the Mann-Whitney-Wilcoxon U test. A total of 233 patients who had radiographs of their hands and feet at both baseline and 12 months, which were of sufficient quality for scoring, were included in the analysis. During the 12-month observational period, patients in the triple-positive group had greater radiographic progression (1.8; 95% CI, 0.9-2.6; SE=0.4), measured as the change in total SvH score, as compared with the single-positive (1.2; 95% CI, 0.1-2.4, SE=0.5) and AMPA-negative (1.0; 95% CI, -0.2 to 2.3; SE=0.5) groups. In addition, there was no significant difference in radiographic progression in the single-positive vs AMPA-negative group (-0.2; 95% CI, -1.1 to 0.7; SE=0.4).

One study limitation included the fact that only autoantibodies to modified peptides derived from vimentin, as opposed to fibronectin and alpha-enolase, were considered. Furthermore, patients in the study were almost exclusively treated with synthetic disease-modifying antirheumatic drugs (DMARDs) and the findings may not be applicable to patients receiving biologic DMARDs.

“Our study adds to the published literature by showing that patients with antibodies to citrullinated, carbamylated, and acetylated peptides have a higher rate of radiographic progression than do those with antibodies to citrullinated peptides alone,” the researchers concluded. “We believe that further prospective work is required to understand the effects of multiple autoantibody specificities in patients with [RA] and whether such baseline autoantibody status should be used to stratify patients with [RA] in therapeutic trials.”

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

Reference

Nijjar JS, Morton FR, Bang H, et al; on behalf of the Scottish Early Rheumatoid Arthritis Inception Cohort Investigators. The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study. Lancet Rheumatol. Published online January 27, 2021. doi:10.1016/S2665-9913(20)30381-7