This is one reason researchers establish narrow and specific groups in clinical trials, such as in APIPPRA. Disease in patients may exist on a pathogenic spectrum with RA, and some cases eventually progress to full-blown disease. However, Dr. Cope argues that it’s misleading to characterize these patients as having early RA. “We see people in clinic without swelling in their joints on clinical exam or ultrasound. If you stick to the classification for the disease, they [don’t] fulfill it.”
Dr. Emery acknowledges concerns of potential overtreatment. But he contends that targeting specific subgroups most appropriate for potential interventions could improve the risk/benefit ratio. For example, although about 50% of patients with inflammatory joint pain and positive antibodies go on to develop clinically defined RA, this rate is higher when other factors are considered, including high-titer autoantibodies, early morning stiffness and increased erythrocyte sedimentation rates.8
Some have also critiqued prevention studies by arguing that they may simply be temporarily suppressing disease rather than truly changing the disease trajectory. But even if further studies show that these agents don’t ultimately prevent RA, they still may help decrease some patients’ joint damage and improve their quality of life.
Dr. Cope notes that the field may move ultimately toward a different model of treatment, with cycles of treatment holidays and periods of treatment if symptoms return. With this on/off approach, clinicians may be able to limit symptom burden and prevent patients from developing clinical synovitis and fully qualifying for an RA diagnosis.
Current Approaches
Studies like APIPPRA may help inform future guidelines for patients at high risk for RA.
“In five or 10 years, I suspect we will have a much clearer definition of this at-risk phase, which will inform potential treatment based on symptom burden, clinical exam, autoantibodies, imaging and, probably, other [factors] as well,” says Dr. Cope. “Then we’ll be in a much better place to assess who needs treatment and who doesn’t.”
The best approach for managing a patient at high risk for RA is currently unknown. Clinicians need to use an individualized, shared decision-making approach with patients, which may vary based on many factors.
From a practical standpoint, abatacept is currently unlikely to be an available treatment option for most patients in the U.S. or the U.K. outside clinical studies. Dr. Sparks notes that it’s reasonable to monitor closely and not treat with any disease-modifying anti-rheumatic drug (DMARD) in these patients. He shares that he probably wouldn’t consider hydroxychloroquine due to results of the StopRA study. “If I were going to use a DMARD, it would probably be methotrexate,” he says. “Even if it doesn’t delay RA onset, it will help reduce joint pain and improve quality of life.”
