Individuals with rheumatoid arthritis who have antifibrillar collagen type II antibodies appear to have a unique disease phenotype characterized by acute but transient inflammation around the time of diagnosis, as well as a favorable prognosis, according to findings from a retrospective cohort study.

The antifibrillar collagen type II (anti-CII) phenotype also differed from the phenotype of individuals with anti–cyclic citrullinated peptide 2 (anti-CCP2) antibodies who typically exhibit inflammatory markers and higher disease activity later in the disease course, reported Vivek Anand Manivel of Uppsala (Sweden) University and his colleagues (Ann Rheum Dis. 2017 Mar 23. doi: 10.1136/annrheumdis-2016-210873 ).

Mr. Manivel and his coauthors retrospectively identified 773 patients who had been admitted into the Swedish EIRA (Epidemiological Investigation in Rheumatoid Arthritis) study during 1996-2005 and linked them to 5-year follow-up data in the Swedish Rheumatology Quality Register. They all met 1987 American College of Rheumatology RA classification criteria, had baseline testing for anti-CII and anti-CCP2 antibodies, and had had symptoms for less than 1 year prior to diagnosis.

Overall, the investigators detected anti-CII positivity in 6.6% and anti-CCP2 in 57.9%, including only anti-CII antibodies in 2.6%, only anti-CCP2 in 54%, double positivity in 3.9%, and double negativity in 39.4%. A control group of 960 patients from the Swedish general population who were matched for age, locality, and sex were positive for anti-CII in 1.6% and anti-CCP2 in 1.7%.

Significant differences were discovered between anti-CII positive and negative groups for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC), and Disease Activity Score encompassing 28 joints (DAS28). Anti-CII seropositive patients had higher CRP at 0-6 months, higher ESR at 0-3 months, a higher SJC at 0-6 months, and a higher DAS28 at 0-3 months.

“Anti-CCP2 [seropositivity] on the other hand was associated with higher disease activity later during the 5-year follow-up, and with CRP and ESR during the full period,” the investigators wrote.

The same respective phenotypic patterns occurred when the comparisons were limited to patients with anti-CII positivity alone or anti-CCP2 positivity alone, the investigators noted. However, “patients in the anti-CII and anti-CCP2 double-positive group mainly followed the anti-CII pattern, with early but not late increased values for CRP, ESR, DAS28, and DAS28CRP, but with a mixed pattern for SJC.”

In comparisons where baseline clinical and laboratory measures were associated with anti-CII or anti-CCP2 positivity, anti-CII was more often associated with favorable late changes in CRP, ESR, SJC, TJC, DAS28, DAS28CRP, Health Assessment Questionnaire, and pain and global measurements on a visual analog scale when compared with antibody double-negative patients. There were fewer changes in clinical and laboratory measures associated with anti-CCP2 positivity. These significant changes associated with anti-CII positivity were always larger improvements than were seen for antibody double-negative patients, whereas the significant changes observed with anti-CCP2 patients were always smaller improvements than those for antibody double-negative patients.

Moderate or good European League Against Rheumatism responses were significantly associated with anti-CII positivity at 12, 24, 36, and 60 months, whereas they were negatively associated with anti-CCP2 positivity at 36 and 60 months.

Overall, the findings of the study show that since “anti-CII-positive patients with RA have an acute onset, but favorable prognosis” and anti-CCP2 is associated with poor prognosis, “the combined analysis of anti-CII and ACPA/anti-CCP2 may be a new two-dimensional tool for predicting the prognosis and choosing therapy in newly diagnosed patients with RA,” the authors suggested.

The study was funded by grants from the Swedish Research Council, Swedish Rheumatism Association, King Gustav Vth 80-Year Foundation, and Uppsala County Council. Dr. Manivel and his coauthors reported no relevant financial disclosures.