By prospectively following this cohort and identifying the 131 patients who ultimately developed clinical arthritis, the model demonstrated very good predictive ability (i.e., the intermediate risk group had a hazard ratio of 4.5, and the high risk group had a hazard ratio of nearly 15).4
One can certainly imagine how such predictive models could be helpful to clinicians and patients in anticipating the probability that clinical manifestations of RA will develop. One can also envision using such models to identify patients who are at high risk of developing clinical disease so they may be enrolled in intervention studies looking to prevent the onset of RA.
Prevention Studies
Several such studies have been done, or are in process, on this subject. For example, in the PRAIRI study, 82 patients with both positivity for ACPAs and RF, but without clinical arthritis, were randomized to receive a single infusion of 1,000 mg of rituximab or placebo.5 These patients were then followed over time, with a mean follow-up of 29 months.
The rituximab-treated group showed a 12-month delay in the development of arthritis compared with the placebo group at the point when 25% of the subjects had developed arthritis. Although risk of arthritis development over the total follow-up time after a single infusion was not statistically significant between the two groups (40% in the placebo group, 34% in the rituximab group), this trial provides some evidence that treatment of pre-clinical RA patients with a B cell-directed therapy, such as rituximab, may help delay the onset of clinical disease.5
Similarly designed trials are now underway with hydroxychloroquine, methotrexate, abatacept and even statins (given the potential immunomodulatory effects of this class of medication).
Dr. Deane noted there are several ways to look at prevention, but perhaps the best operational definition is to stop or delay the appearance of the first swollen joint on exam and, in essence, define success as stopping an individual from manifesting clinical RA.
He explained that there are several challenges rheumatologists must face in achieving these goals. One is understanding each step of the pathophysiologic cascade that ultimately leads to the development of RA. Others are selecting the right kinds of patients to enroll in early intervention trials and having clear ways to measure success. The more the meaning of such terms as pre-clinical RA can be kept uniform and accurate across studies and in the literature, the better that researchers will be able to compare one preventive treatment to another and see if there is efficacy.
