medwireNews: The majority of people with anti-cyclic citrullinated peptide (CCP)2 antibodies and musculoskeletal symptoms without clinical synovitis have a period of subclinical synovitis that precedes inflammatory arthritis, research shows.
This preclinical period may be predicted by the presence of anti-CCP3 antibodies, suggesting that identifying patients with musculoskeletal symptoms who are positive for both anti-CCP2 and anti-CCP3 but with no clinical synovitis “may represent the optimal ‘window of opportunity’ for intervention to prevent joint disease,” write Paul Emery (University of Leeds, UK) and co-authors in Rheumatology.
Emery and team reviewed ultrasound scans from 97 such individuals, defined as CCP2+ at-risk, who ultimately progressed to inflammatory arthritis.
Of these, 77.3% had ultrasound subclinical synovitis, which was first detected a median of 26.5 weeks before the development of inflammatory arthritis.
The wrist was the most common location for subclinical synovitis, with 60.0% of affected participants positive at this site, followed by metacarpophalangeal joints (40.0%), metatarsophalangeal joints (29.3%), proximal interphalangeal joints (22.7%), knees (8.0%), and elbows and ankles (1.3% each).
The researchers then reviewed longitudinal ultrasounds from 220 CCP2+ at-risk individuals who had no baseline ultrasound abnormalities and found that 31.4% subsequently developed ultrasound synovitis, at a median of 56.4 weeks from baseline after a median of two ultrasound scans. These patients had a median of two joints affected.
Multivariate analyses revealed that the presence of anti-CCP3 antibodies was the only variable significantly associated with the development of ultrasound synovitis, with an odds ratio of 4.75.
Indeed, 18.9% and 34.2% of individuals positive for both anti-CCP2 and anti-CCP3 antibodies developed subclinical synovitis at 1 and 2 years, respectively.
This was significantly higher than the corresponding rates of 6.4% and 10.1% observed among the people who were positive for anti-CCP2 but negative for anti-CCP3.
Of note, neither the presence of a high level of anti-CCP2 antibodies nor that of rheumatoid factor predicted the development of ultrasound subclinical synovitis.
Emery et al conclude that the majority of CCP2+ at-risk individuals who progress to inflammatory arthritis go through a stage of ultrasound subclinical joint inflammation that represents “a distinct and important stage of the RA [rheumatoid arthritis] ‘continuum’.”
They add: “Anti-CCP3 antibodies have a potential role in the identification of CCP2+ individuals who are about to develop clinical or subclinical RA-related joint inflammation (i.e., before the ‘second hit’ in RA pathogenesis occurs).”
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