The elimination of anticitrullinated vimentin antibodies during early antirheumatic therapy in rheumatoid arthritis patients may significantly increase the likelihood of positive radiographic outcomes, according to findings from a longitudinal cohort study.

“The development of serological tests for [autoantibodies recognizing citrullinated proteins (ACPA)] detection have improved the ability to diagnose rheumatoid arthritis [RA] at an early stage and to identify patients at increased risk of a severe disease course,” wrote lead author Dr. Alf Kastbom of the Karolinska Institute in Stockholm, and his associates (Ann. Rheum. Dis. 2014 Dec. 30 [ doi:10.1136/annrheumdis-2014-205698]). “These clinically very useful tests do not, however, formally address the question of which specific citrullinated autoantigens are targeted.”

Dr. Kastbom and his coinvestigators longitudinally analyzed serum samples from 316 of 487 patients with early RA (symptoms < 1 year) who had participated in the Swedish Farmacotherapy (SWEFOT) trial , a randomized, nonblinded trial. These 316 patients had baseline and 3-month serum samples available that were analyzed for any antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides that were derived from vimentin (cVim), fibrinogen (cFib), and alpha-enolase (CEP-1).

For the first 3 months, all patients received methotrexate. Next, patients who were deemed “methotrexate monotherapy–inadequate responders” were subsequently randomized into cohorts that received add-on therapy with either sulfasalazine and hydroxychloroquine or infliximab. The investigators again assessed ACPA levels at 12 and 24 months after commencement of therapy in these subjects and used this 2-year follow-up period to compare proportions of antibody-positive patients and relative changes in antibody levels across ACPA specificities, as well as therapeutic responses and radiographic progressions.

Dr. Kastbom and his coauthors found that changes in antibody status within the first 3 months were most closely associated with radiographic progression of RA over the 2-year study period. Specifically, subjects who experienced significant decreases in anti-cVim antibodies in the first 3 months had lower rates of radiographic progression and lower total van der Heijde modified Sharp score (SHS) after 2 years than did those whose anti-cVim antibody levels remained positive (P = .012 and P = .015, respectively). Anti-cVim antibody results were also adjusted for baseline 28-joint disease activity score, baseline erosions, current smoking status, sex, and European League Against Rheumatism response at 3 months (P = .005 for SHS progression > 1 and P = .013 for SHS progression > 5, respectively).

However, no significant relationships with radiographic progression were found in the anti-cFib and anti-CEP-1 antibody seroreversions. Median antibody levels of all tested ACPAs declined during initial methotrexate therapy and after commencement of add-on therapy, but the investigators found no significant association between treatment regimen and radiographic progression.

“It is intriguing to see that our study clearly demonstrates an association between the early disappearance of specific anti-cVim antibodies and less radiological progression,” wrote Dr. Kastbom and his colleagues, adding that the findings of this study should “encourage further work to explore the prognostic potential of repeated measurements of different ACPA specificities in early RA.”

This study was financed by grants from European Union–funded FP7 projects and several Swedish institutions. Several coauthors also disclosed individual ties to various pharmaceutical companies.


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