ACR 2010: Aggressive Therapy Leads to Remission in Probable Rheumatoid Arthritis

The trend in the field of rheumatoid arthritis (RA) is to favor early and aggressive treatment to improve outcomes once RA is diagnosed. A study presented at the 2010 Annual Meeting of the American College of Rheumatology suggests that treating even earlier (ie, patients with early arthritis as well as those with undifferentiated arthritis who don’t meet the criteria of RA) can achieve impressive gains in remission.

The IMPROVED study showed that four months of treatment with methotrexate (MTX) and a tapered dose of prednisone achieved remission in 63% of 422 patients (261 patients with early RA and 161 with undifferentiated RA). “This is an excellent result, much higher than the 30% to 40% remission rates we see in definite RA,” said Alan Matsumoto, MD, moderator at a press conference at the ACR Annual Meeting where these results were released.

“Three or four years ago, we didn’t talk about remission in RA. This study shows a 63% remission rate. I would like to do even better and improve that remission rate and then be able to take patients off of drugs,” said senior author of this paper, K.V.C. de Boer, MD, Leiden University Medical Center, The Netherlands.

“This is the first study to treat early RA and undifferentiated RA patients with progressive combination therapy, which was previously reserved for active, more advanced RA,” said lead author C.F. (Renee) Allaart, MD, Leiden University Medical Center.

IMPROVED is a multicenter, single-blind, clinical study with an open-label induction phase of MTX 25 mg/week plus prednisone 60 mg/day tapered to 7.5 mg/day in seven weeks. The goal of treatment was to achieve a Disease Activity Score (DAS) <1.6 signifying remission. The study has a second phase to determine whether patients who achieve clinical remission can be tapered from their drugs. In the second phase of the study (not yet completed), patients who do not achieve clinical remission are randomized to multi-disease modifying anti-rheumatic drug or to MTX plus adalimumab if DAS > 1.4 after four months.

“The second randomized phase of the study will determine whether there is still a place for conventional DMARD therapy after failure on methotrexate and prednisone, or whether anti-TNF is still the best option for induction remission,” Allaart said.

At baseline, patients with undifferentiated arthritis were younger, less often positive for rheumatoid factor, and had lower scores on DAS and the Health Assessment Questionnaire (HAQ) compared with their counterparts with early RA. After four months of treatment, clinical remission was achieved in 66.5% of the undifferentiated arthritis patients and 58.6% of those with definite RA.

The major factor predicting remission in RA was lower baseline DAS; the lower the score, the faster the remission, de Boer said. Also males and younger patients were more likely to achieve remission, she said. Anti-cyclic citrillunated peptide antibody (ACPA) positivity was an independent predictor for achieving remission only in undifferentiated arthritis patients .

Previously, the PROMPT study by the same group of investigators compared aggressive treatment with high-dose MTX and prednisone versus placebo in patients with probable RA. In that study, treatment was less beneficial in ACPA-negative undifferentiated arthritis patients.

de Boer said that these findings suggest that ACPA-negative undifferentiated arthritis may be a different disease that requires different therapy than ACPA-positive.