Published: Apr 19, 2014
By Nancy Walsh, Senior Staff Writer, MedPage Today
Action Points
- A risk score encompassing clinical characteristics, serologic findings, and imaging tests could be used to predict which patients with positive antibodies to anti-cyclic citrullinated peptide are likely to go on to develop rheumatoid arthritis (RA), researchers found.
- Note that in the multivariate model, features that were associated with progression to RA were: tenderness of hand or foot joints, early morning stiffness ≥30 minutes, high-positive anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor, and positive ultrasound findings.
A risk score encompassing clinical characteristics, serologic findings, and imaging tests could be used to predict which antibody-positive patients are likely to go on to develop rheumatoid arthritis (RA), researchers reported.
Among a cohort of patients with nonspecific musculoskeletal pain who were positive for the RA-specific anti-citrullinated protein antibodies (ACPA), 62% of those with high scores of 3 or higher (out of 5) progressed to RA, mostly within a year, according to Paul Emery, MD, of the University of Leeds, and colleagues.
In contrast, among those with scores of zero, none progressed, and among those with scores of 1 or 2 — reflecting moderate baseline risk — 31% progressed, the researchers reported online in Annals of the Rheumatic Diseases.
It has become increasingly clear in recent years that full-blown RA is preceded by a preclinical phase characterized by seropositivity for ACPA and/or rheumatoid factor, often accompanied by musculoskeletal complaints.
“Identifying patients at this early phase should produce the best clinical outcome by early diagnosis and treatment and may also permit the possibility of preventive therapy,” Emery and colleagues observed.
To explore the possibility of this, the researchers enrolled 100 patients who had no apparent swollen, inflamed joints but who were ACPA-positive and reported pain and other symptoms.
Participants underwent detailed clinical and serologic examinations at baseline, along with power Doppler ultrasound evaluation of the wrists and hands. They then were seen every 3 months in the first year, and then as needed or until inflammatory arthritis was diagnosed on the basis of at least one swollen and tender joint.
After a median of 7.9 months, 50 of the patients had progressed to inflammatory arthritis. A total of 34 were diagnosed within 1 year, and 44 within 2 years.
Rheumatoid arthritis was the diagnosis in 43, while the remainder were classified as having undifferentiated inflammatory arthritis.
In a univariate analysis, clinical features that were associated with progression were early morning stiffness of 30 minutes or longer and tenderness of the small joints.
Biomarkers that were predictive included rheumatoid factor positivity, high titers of ACPA or rheumatoid factor, presence of the HLA-DRB1 shared epitope, and positive ultrasound findings.
The researchers then constructed risk models for multivariable analyses, with the main model including tenderness of the small joints, 30-minute early morning stiffness, and high-titer ACPA and/or rheumatoid factor. That model also included positive ultrasound findings rather than presence of the shared epitope because of cost and convenience, while additional models included the shared epitope without ultrasound, and then both.
These additional models provided risk assessments that were similar to the main model, with no patients having scores of zero showing progression, 30% to 50% of those having moderate scores progressing, and 62% to 72% of those with high scores having progression at some point during follow-up.
However, including the shared epitope in the model was more sensitive for identifying low risk, according to the researchers.
“These results would suggest that individuals may be screened at presentation with a simplified model using clinical data and antibodies and those with moderate risk could be referred for further advanced testing,” they noted.
The study confirmed the hypothesis that ACPA-positive patients with musculoskeletal pain and stiffness have a significant likelihood of progressing to RA.
“The risk score derived from this cohort is a step towards achieving a personalized medicine approach to identify those patients at an early stage,” Emery and colleagues wrote.
A limitation of the study was its relatively small size. In addition, the risk score needs to be validated in a larger population.
The study was supported by the National Institute for Health Research (NIHR), Arthritis Research UK, and AbbVie.
One co-author reported relevant relationships with NIHR and Arthritis Research UK.