OP-0040 – Drug-Free Remission after Treatment Discontinuation Following One Year of Methotrexate or Placebo Treatment in Undifferentiated Arthritis Patients
Visser, Ronday, van Dongen, van Aken, Lard, Hulsmans, Speyer, Westedt, Peeters, Toes, Breedveld, Allaart, Huizinga; Leiden, the Netherlands
Objectives
The “PRObable rheumatoid arthritis: Methotrexate vs. Placebo Treatment” (PROMPT) study demonstrated that early treatment of synovitis, even in those without sufficient signs and symptoms for classification as rheumatoid arthritis, may lead to a delay in diagnosis and less long-term joint damage. The authors presented outcomes for the 12 months after discontinuation of methotrexate for those patients who did not meet classification criteria for RA during the study.
Methods
The methods of the PROMPT study have been described here previously. For these analyses, patients who had not progressed to RA at 12 months had their methotrexate discontinued and were followed for out to a maximum of 30 months from randomization for flare, at which time treatment was reintroduced.
Results
110 patients were randomized to receive either methotrexate or placebo. At 12 months, 39 (71%) of the patients in the methotrexate group vs. 21 (38%) of the placebo group were able to discontinue methotrexate. Of those initially randomized, 18 (33%) of the methotrexate group vs. 17 (31%) of the placebo group were in sustained, drug-free remission at 12 months. Univariate predictors of drug-free remission were higher age, shorter duration of symptoms (< 6 months), lack of baseline erosions, and lack of anti-CCP antibodies. In multivariable models including all of these factors, only lack of baseline erosions and lack of anti-CCP antibodies were significant predictors of sustained drug-free remission. Disease activity scores, either at baseline or change, were not predictive of drug-free remission in univariate or multivariate models.
Conclusion
Discontinuation of treatment in early undifferentiated arthritis patients in remission can be discontinued with success in patients without baseline erosions or anti-CCP antibodies. In patients with these risk factors, sustained drug-free remission is unlikely.
Editorial Comment
The PROMPT study is unique, and has enlightened the treatment of early polyarthritis. The most important aspect of this abstract is the high flare rate in the anti-CCP positive patients with discontinuation of methotrexate, suggesting that this group of patients deserves continued treatment, regardless of disease activity measures. Those without anti-CCP antibodies may still require restarting therapy, but have a better chance of not requiring therapy. However, early treatment with methotrexate did not seem to have influenced drug-free remission rates, as the frequency of drug-free remission was equal in the methotrexate and placebo groups. This could suggest that the “window of opportunity” for therapy to alter the course of RA lies even earlier than the undifferentiated arthritis phase.
