High anti-CCP, pain in hands, feet linked to increased risk for inflammatory arthritis
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High anti-cyclic citrullinated peptide levels and pain in the hands or feet indicate an increased risk for progression to inflammatory arthritis, especially rheumatoid arthritis, according to data published in Arthritis Research & Therapy.
“We studied individuals presenting to primary care — largest cohort studied — with new non-specific musculoskeletal symptoms, without clinical arthritis, and determined what their risk of progression to inflammatory arthritis was,” Paul Emery, MD, of Chapel Allerton Hospital, University of Leeds, in the United Kingdom, told Healio. “Individuals with a high anti-cyclic citrullinated peptide (anti-CCP) titer and pain in hands/feet had an increased likelihood of progression to inflammatory arthritis (IA). Those with a low anti-CCP titer without pain in hands/feet were unlikely to progress.”
To examine the link between patient factors among those with new musculoskeletal symptoms and the progression to inflammatory arthritis, Emery and colleagues analyzed data from a prospective cohort in an observational study adopted by the National Institute of Health Research. A total of 6,780 patients aged 16 years and older with new non-specific musculoskeletal symptoms, and no clinical synovitis, were recruited from U.K. primary care centers from July 2007 to May 2019.
Among the recruited patients, 3% tested positive for the anti-CCP2 assay (anti-CCP+) and were invited to Leeds for follow-up. Meanwhile, those with a negative result (anti-CCP–) completed a 1-year questionnaire while general practitioners were asked to confirm whether the participant had been diagnosed with inflammatory arthritis by a rheumatologist. The researchers used multivariable regression analysis to determine predictors for progression to inflammatory arthritis.
According to the researchers, 45% of those who were anti-CCP+ progressed to inflammatory arthritis, with 84% of them doing so in less than 12 months. Among the 68 who progressed to inflammatory arthritis, 63 had RA, two were diagnosed with polymyositis, two had undifferentiated inflammatory arthritis, and one was diagnosed with spondyloarthritis.
In the multivariate model, high anti-CCP+ levels (OR = 9.42; 95% CI, 3.13-28.3), hand pain (OR = 2.74; 95% CI, 1.03-7.27) and foot pain (OR = 4.1; 95% CI, 1.59-10.54) were predictive of progression to inflammatory arthritis. Among low-level anti-CCP+ participants, the absence hand or foot pain demonstrated a negative predictive value of 96% for progression.
Follow-up data were available for 5,640 anti-CCP– participants, of whom 0.93% were diagnosed with inflammatory arthritis. Pain in the hands (OR = 2.51; 95% CI, 1.17-5.39) or knees (OR = 3.03; 95% CI, 1.47-6.25) was associated with inflammatory arthritis development within 12months.
“In a large population of anti-CCP-negative patients, only those with hand or knee pain were at increased risk of progression, albeit, at a much-reduced rate compared to CCP positive individuals,” Emery said. “The study confirmed CCP2 as useful screening test, and provides an algorithm for deciding on referral to secondary care based on data.”
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