Rheumatologists won’t always know a patient’s serological status when he or she presents with musculoskeletal symptoms that could point to elevated risk of RA. If they do show up at the clinic with early signs of risk, it’s important to test them, says Prof. Emery.
“It’s worth fully assessing patients, and if they are at high risk, then weight loss and smoking cessation should certainly be advised, although definitive evidence of the benefit is currently being investigated,” he says. Groups of patients with arthralgia that could be clinically suspect are now being studied to clarify whether or not symptoms alone could point to higher RA risk.20
Subclinical Inflammation
Patients who have symptoms, but haven’t yet progressed to clinical RA, may already have joint inflammation. While a rheumatologist may be able to detect soft-tissue swelling at some point, new imaging techniques could help us spot inflammation earlier, says Prof. Emery.
“Imaging undoubtedly is a key factor in predicting progression, identifying those who will progress, and also the speed at which they will progress,” he says. Different ultrasound techniques have been tested in a Netherlands-based study to see how well they detect joint abnormalities in pre-RA patients who were both seropositive and had arthralgia.21 “Currently, the most effective predictor is the presence of significant power Doppler [or signs of joint abnormalities on a power Doppler scan], which has a hazard ratio of 33 for developing rheumatoid arthritis.”
Magnetic resonance imaging (MRI) has also been tested on ACPA-positive, at-risk patients as a way to spot early synovial inflammation. So far, MRI has been shown to be most effective at detecting synovitis in the small joints of the hands and feet, including anti-CCP positive patients with pain, but not yet clinical arthritis.22 Also, in a large study, MRI showed significant inflammation in 44% of 93 patients with arthralgia.23 However, MRI can also show evidence of synovitis in healthy patients, Ms. Mankia and Prof. Emery say. So MRI may be a highly sensitive, but not highly specific, tool in assessing RA risk, they add.
Other imaging techniques may be more specific, such as macrophage positron emission tomography (PET). One small study of ACPA-positive patients with arthralgia, but not clinical arthritis, showed that PET was highly specific in identifying who would progress.24 PET hasn’t yet been compared with ultrasound and MRI, and both the effects of the radiation dose and the high cost of serial imaging may raise concerns, Prof. Emery says.
Managing Those at Risk
Combined biomarkers of pre-RA may help rheumatologists predict who will develop the disease. New tools are in development to stratify risk. One of the most successful models combines clinical features, serological results, and ultrasound power Doppler signal. Using data from a Leeds University cohort, 72% of the patients identified as high risk did progress to arthritis within two years.25