RA Treatment Strategies
Abstract 657: Evidence for a Window Of Opportunity in a Double-Blind Randomized Clinical Trial in Patients with Undifferentiated Arthritis: The Probable Rheumatoid Arthritis: Methotrexate Versus Placebo Treatment (the Prompt)-Study
AUTHORS: H van Dongen, J van Aken, LR Lard, HK Ronday, HMJ Hulsmans, I Speyer, M-L Westedt, AJ Peeters, CF Allaart, REM Toes, FC Breedveld, TWJ Huizinga.
BACKGROUND: The treatment of RA has increasingly focused on earlier definitive intervention with DMARD therapy. Several studies have suggested that a “window of opportunity” exists in which to institute therapy that will affect the longer term outcome of disease. In this study from the Netherlands, the investigators sought to determine the impact of DMARD therapy with methotrexate in patients with the earliest stage of undifferentiated inflammatory arthritis, even before patients may meet the definition of RA by ACR criteria.
METHODS: The PROMPT study was a prospective double-blind placebo-controlled randomized multicenter study in the Netherlands of 110 patients with undifferentiated arthritis. Treatment was instituted with MTX 15 mg/wk or placebo with dose-escalation every 3 months if a DAS was > 2.4. If a patient fulfilled criteria for RA at any point, he/she was then changed to receive MTX. After 12 months of treatment, study medication was tapered off and patients were followed for a total of 30 months. Outcome measures included fulfillment of the ACR criteria for RA, radiographic progression based on every 6 month X Rays of the hands and feet. The mean number of swollen and tender joints was only 2-3; 40% of patients were RF positive; and only 4-6% had evidence of erosions at baseline.
RESULTS: After 30 months, in the MTX-group, 22/55 patients had progressed to RA versus 29/55 in the placebo-group, the criteria were fulfilled at a later time point (p=0.04), and patients showed less radiographic progression over 18 months. The progression to RA and in joint damage was retarded only in patients with anti-CCP but not in patients without these antibodies.
CONCLUSIONS: The authors conclude that there intervention using early DMARDS in some patients with early undifferentiated arthritis will decrease the development into RA and will decrease radiographic progression. Their results suggest that this is possible in patients who present with anti CCP antibodies. Thus as there is a window of opportunity in the institution of definitive therapy in patients with established RA, there may also be a window of opportunity in patients who have not yet declared themselves with definitive disease.
EDITORIAL COMMENT: These results strongly support the fact that the treatment of patients who present with undifferentiated arthritis with only a few swollen and tender joints may be appropriate for institution of MTX therapy. Moreover the strategy to base treatment dose increases on an objective measurement, as done here with the DAS, may also be important. These results furthermore support the use of anti CCP antibodies in defining even “pre-RA”. Importantly institution of DMARD therapy may even be able to prevent these patients from going on to develop disease and to decrease joint damage. It is also important to note that in patients with responses to treatment, that methotrexate tapering was allowed, supporting the possibility of an “induction regimen” that can alter the course of disease and ultimately allow treatment withdrawal in some patients.
