Early Rheumatoid Arthritis May Benefit from Disappearance of Anti-Citrullinated Peptide Antibodies

The disappearance of particular anti-citrullinated peptide antibodies (ACPA) reactivities may be beneficial in early rheumatoid arthritis (RA), according to findings published in Annals of the Rheumatic Diseases.

Researchers from various institutes in Sweden observed 316 patients for 2 years in order to determine the relationship between changes in antibody levels toward citrullinated peptides derived from different candidates autoantigens and therapeutic outcome in early RA. The study participants had early RA and were enrolled in the Swedish Farmacotherapy (SWEFOT) trial. The patients had never been treated with disease modifying anti rheumatic drugs (DMARD) and had a symptom duration of RA of less than 1 year. They were analyzed at baseline and after 3 months for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib), and α-enolase (CEP-1).

At the 3 month follow up mark, methotexate monotherapy inadequate responders were randomized to add on therapy with sulfasalazine and hydroxychloroquine or infliximab. These patients also were assessed for ACPA at 12 and 24 months. The researchers then compared the proportion of antibody positive patients and relative changes in antibody levels across ACPA specificities and related therapeutic response and radiographic progression.

At the end of the 2 year follow up, the proportions of positive testing patients was significantly reduced with respect to antibodies to cVim, cFib, and CEP-1. However, anti CCP antibody occurrence was stable throughout the observation period. Most often, the researchers discovered turning anti cVim antibody negative, and the anti cVim antibody seroreversion during the first 3 months was linked to reduced 2 year radiographic progression compared to the patients who remained positive. The average levels of all of the observed ACPA levels demonstrated similar decline during the initial methotrexate therapy and following response to the additional therapy. There was no significant relationship between treatment regimen or radiographic progression.

“The effect of early anti rheumatic therapy on circulating ACPAs is markedly different across different antibody specificities with regards to seroreversion,” the authors concluded in their paper. “The association between the disappearance of anti cVim antibodies after 3 months and less radiological progression at 24 months should encourage further work to explore the prognostic potential of repeated measurements of different ACPA specificities in early RA.”

The researchers noted that other studies, such as 2 smaller studies done in North America, observed stable occurrences of autoantibodies to vimentin derived citrullinated antigens over 3 and 7 years of early RA, respectively. However, the researchers also commented that there are a number of reports circulating which suggest a more pronounced association between antibodies to vimentin derived citullatined antigens and radiological progression.