Probable RA Treated With Methotrexate or Placebo
Probable RA Treated With Methotrexate or Placebo
Objective To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo.
Methods 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)).
Results 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment.
Conclusions After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.
Patients with inflammatory arthritis may present with undifferentiated arthritis (UA) not fulfilling any classification criteria. Although UA may be a self-limiting disease, a considerable proportion of patients with UA has an early manifestation of rheumatoid arthritis (RA). For patients with recent-onset RA, a timely start of treatment with disease-modifying antirheumatic drugs (DMARDs) has proved to be crucial for achieving better clinical and radiographic outcomes. Therefore starting antirheumatic treatment already in UA might result in even more sustained benefits and potentially a chance for cure.
In the PROMPT study, we showed that treatment with methotrexate (MTX) compared with placebo for 1 year did not prevent, but (in anti-citrullinated protein antibody (ACPA)-positive patients at least) delayed, the development of UA into RA. MTX reduced signs and symptoms at 12 months and radiographic progression at 18 months—again, particularly in ACPA-positive patients with UA. It remains to be determined whether this very early introduction of MTX has benefits in the long term.
In this study, the effect of early MTX treatment on clinical and radiological outcomes was assessed after 5 years. In addition, we identified predictors for disease progression to classifiable RA and for persistent remission in patients with UA. Finally, we re-evaluated current and previous study results using the 2010 classification criteria for RA to see whether MTX monotherapy in patients who fulfil the 2010 criteria and have relatively low disease activity is sufficient to achieve remission.
Abstract and Introduction
Abstract
Objective To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo.
Methods 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)).
Results 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment.
Conclusions After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.
Introduction
Patients with inflammatory arthritis may present with undifferentiated arthritis (UA) not fulfilling any classification criteria. Although UA may be a self-limiting disease, a considerable proportion of patients with UA has an early manifestation of rheumatoid arthritis (RA). For patients with recent-onset RA, a timely start of treatment with disease-modifying antirheumatic drugs (DMARDs) has proved to be crucial for achieving better clinical and radiographic outcomes. Therefore starting antirheumatic treatment already in UA might result in even more sustained benefits and potentially a chance for cure.
In the PROMPT study, we showed that treatment with methotrexate (MTX) compared with placebo for 1 year did not prevent, but (in anti-citrullinated protein antibody (ACPA)-positive patients at least) delayed, the development of UA into RA. MTX reduced signs and symptoms at 12 months and radiographic progression at 18 months—again, particularly in ACPA-positive patients with UA. It remains to be determined whether this very early introduction of MTX has benefits in the long term.
In this study, the effect of early MTX treatment on clinical and radiological outcomes was assessed after 5 years. In addition, we identified predictors for disease progression to classifiable RA and for persistent remission in patients with UA. Finally, we re-evaluated current and previous study results using the 2010 classification criteria for RA to see whether MTX monotherapy in patients who fulfil the 2010 criteria and have relatively low disease activity is sufficient to achieve remission.
