PARIS, France—Undifferentiated arthritis (UA) patients who are anticitrulline-peptide antibody (ACPA) negative, older, have no or low radiographic damage at baseline, and have shorter disease durations are more likely to achieve disease free-remission following methrotrexate (MTX) therapy, according to the latest data from the Probable rheumatoid arthritis Methotrexate versus Placebo Therapy (PROMPT) study. The findings were presented at the annual European League Against Rheumatism (EULAR) meeting in Paris.1

"MTX discontinuation can be tried in ACPA negative UA patients without baseline radiographic damage, but MTX should be continued in ACPA positive patients, irrespective of the DAS."—Karen Visser, MD
Researchers led by Karen Visser, MD, of Leiden University Medical Center in The Netherlands concluded, "MTX discontinuation can be tried in ACPA-negative UA patients without baseline radiographic damage, but MTX should be continued in ACPA-positive patients, irrespective of the DAS (disease activity score)."?

PROMPT study highlights predictors of drug-free remission

A total of 110 UA patients were randomized to 1-year treatment with MTX at 15 mg/week or to placebo. The dose was increased to MTX 30 mg/week or to 12 placebo tablets/week based on 3-monthly calculations of DAS, aiming at a DAS ≤2.4.

At 12 months, 60 patients whose UA had not progressed to arthritis were tapered and discontinued MTX, irrespective of DAS. If a flare occurred and arthritis was diagnosed according to the American College of Rheumatology's criteria, MTX was (re)introduced. The clinical outcome of the patients was then assessed, and baseline determinants of achieving drug-free remission were investigated.

At 12 months, 71% of the patients in the original MTX group discontinued the study medication, compared with 38% of the patients in the original placebo group. Ten patients who discontinued MTX were ACPA-positive compared with one patient in the placebo group.

Of the patients who stopped MTX, 46% achieved drug-free remission after 30 months versus 81% of the patients who discontinued placebo, the study showed. In addition, 20% of the 10 ACPA-positive patients who discontinued MTX achieved drug-free remission after 30 months. By contrast, 55% of the 29 ACPA-negative patients who discontinued MTX achieved drug-free remission after 30 months. Moreover, those ACPA-positive patients showed a mean (SD) SHS progression of 2.7 (3.3) after 30 months compared with a mean progression of 0.6 (1.5) in their ACPA-negative counterparts.

Translating research into practice

The researchers concluded that drug-free remission is predicted by a negative ACPA status, not by DAS at baseline and 12 months, or by change in DAS in first year. None of the patients with drug-free remission at 30 months had a baseline SHS score higher than the smallest detectable change of 2.8, compared with 30% of the patients who flared or had persistent UA. In addition, age >65 years was associated with a greater chance of drug-free remission compared with ages 40 to 65 years or age <40. Patients with symptom duration <6 months were more likely to achieve drug-free remission compared with those patients with disease duration >12 months.

Reference
1. Visser K, Ronday K, van Dongen H, et al. Drug-free remission after treatment discontinuation following one year of methotrexate or placebo treatment in undifferentiated arthritis patients. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Abstract OP-0040.