New treatments have dramatically improved rheumatoid arthritis disease outcomes, but most patients still require lifelong therapy. With the ultimate goal of avoiding the disease altogether, several innovative trials have attempted to prevent disease progression from undifferentiated arthritis to classifiable rheumatoid arthritis. Thus far, these trials have been unsuccessful.
In a recent study, however, a new approach to risk stratification has had significant results.
For high-risk patients with undifferentiated arthritis, a one-year course of methotrexate was associated with an absolute risk reduction of 45% in rheumatoid arthritis development.
In addition, rheumatoid arthritis development was significantly delayed in the methotrexate arm compared with the placebo arm and drug-free remission was achieved significantly more often with methotrexate.
Led by Leonie E. Burgers, MD, of Leiden University Medical Center in Leiden, The Netherlands, researchers writing in Arthritis & Rheumatology reached these conclusions after a postrandomization exclusion of uninformative patients from the Probable Rheumatoid Arthritis: Methotrexate versus Placebo Treatment (PROMPT) trial.
The original study, a prospective double-blind, randomized, placebo-controlled multicenter study, evaluated the effect of a 1-year course of methotrexate versus placebo in 110 patients with undifferentiated arthritis. After a follow-up period of 5 years, the original study found that methotrexate had no preventative effect.
However, because only about 30% of patients with undifferentiated arthritis ever progress to rheumatoid arthritis, researchers hypothesized that the inclusion of patients who were not at high risk for rheumatoid arthritis could lead to false-negative results.
In the present study, researchers reanalyzed the PROMPT data using the well-validated Leiden prediction rule, a 9-item instrument that includes clinical and biomarker factors that result in a prediction score ranging from 0 to 14. The current study included those patients from PROMPT who had a prediction score of 8 or higher, which resulted in 22 high-risk undifferentiated arthritis patients. By chance, these high-risk patients had been equally randomized between the 2 treatment arms.
Leonie E. Burgers, Cornelia F. Allaart, Tom W. J. Huizinga, et al. “Brief Report: Clinical Trials Aiming to Prevent Rheumatoid Arthritis Cannot Detect Prevention Without Adequate Risk Stratification: A Trial of Methotrexate Versus Placebo in Undifferentiated Arthritis as an Example.” Arthritis Rheumatol. 2017;69:926-931. doi: 10.1002/art.40062. Epub 2017 Mar 31.
Kevin D. Deane, Christopher C. Striebich, V. Michael Holers. “Editorial: Prevention of Rheumatoid Arthritis: Now Is the Time, but How to Proceed?” Arthritis Rheumatol. 2017;69:873-877. doi: 10.1002/art.40061. Epub 2017 Apr 11.