WASHINGTON, DC—Three-year results from the BeSt study suggest that early induction therapy with infliximab (RemicadeR) plus methotrexate (MTX) can bring about remission in some rheumatoid arthritis (RA) patients. The findings were presented Sunday at the 70th Annual Meeting of the American College of Rheumatology (ACR) in Washington, DC.1

"Data collected over the next years will determine whether treatment-free remission will last, and whether it represents not only clinical but also radiological suppression of disease activity." -- Sjoerd Van Der Kooij, MD
The original BeSt study compared the four most widely used treatment strategies for very early RA in 508 patients: group 1 received standard disease modifying anti-rheumatic drug (DMARD) therapy, starting with MTX; group 2 was assigned to step-combination therapy, which began with MTX only and added other DMARDs and prednisone; group 3 started with a combination of MTX, sulfasalazine, and prednisone; and group 4 started with a combination of MTX and infliximab. For all groups, drug dosages were increased or patients were switched to other agents to achieve an adequate clinical response as measured by disease activity score (DAS)44 <e;2.4. The data reported this year at ACR are from a follow-up of group 4 (MTX/infliximab).

15% of patients remain in remission

After 3 years, 55% of patients in this group were in remission and had discontinued infliximab.   Investigator Sjoerd Van Der Kooij, MD, reported that 15% of patients remain in clinical remission without any drug therapy and with a disease activity score DAS <1.6.

"A window of opportunity exists in which the character of inflammation can be altered with aggressive therapy," said Dr. Van Der Kooij, a rheumatologist at Leiden University Medical Center in Leiden, The Netherlands. "The 3-year follow-up results indicate that initial treatment with MTX and infliximab may alter the course of early RA and, in many cases, move patients into remission." He added that, "data collected over the next years will determine whether treatment-free remission will last, and whether it represents not only clinical but also radiological suppression of disease activity."

Patients received 3 mg/kg of infliximab for 8 weeks and 25 mg per week of MTX. If the DAS was >2.4, infliximab was increased, and if the DAS was <e;2.4 for >e;6 months, the infliximab dose was tapered to zero, and MTX was tapered to 10 mg/week. By year 3, if the DAS was <1.6 for >e;6 months, MTX 10 mg/wk was tapered and discontinued.

If the next DAS was >1.6, MTX 10 mg/week was restarted. Subsequently, if the DAS was >2.4, initially MTX was increased to 25 mg/week, and then infliximab was restarted and increased if necessary. Researchers assessed baseline and 3-year Sharp-van der Heijde scores. Study patients had an average age of 54 years and an average symptom duration of 23 weeks. The majority of patients were rheumatoid factor positive.

Of the 120 patients treated with MTX plus infliximab, 77 were able to discontinue infliximab due to good response. Of these, 67 patients continue on MTX monotherapy. Ten patients had to restart infliximab. Thirty patients failed infliximab plus MTX therapy, including eight who stopped infliximab because of adverse events and went on to other treatments including sulfasalazine.

After 3 years, 63 patients were still off infliximab; 44 of them continue on MTX monotherapy, but 16 patients have discontinued both drugs and remain in sustained, drug-free remission. Two patients are on sulfasalazine and four patients are still receiving infliximab plus MTX.

Best results seen in patients who had least joint damage at study entry

Patients who had the best clinical response on the infliximab and MTX combination had the least amount of joint damage, while half of the MTX/infliximab failures showed progression of radiographic damage. Specifically, mean Sharp-van der Heijde progression was 2.5 after 3 years in responders, 4.7 among those in the continued treatment group, and 6.2 among treatment failures. Those patients who were able to discontinue all drug therapy had no radiographic progression, the study showed.

While the latest results from BeSt are "exciting," Iain B. McInnes, FRCP, PhD, professor of experimental medicine and rheumatology at the University of Glasgow in Scotland, told CIAOMed that "for a small proportion of patients, we can clearly get quite a substantial benefit, but for the majority of patients, we are not really achieving drug-free outcomes."

Still, he said he was cautiously enthusiastic that growing numbers of RA patients will be able to achieve drug-free remissions.

Reference

1. Van Der Kooij SM, Van Der Bijl AE, Alaart CF, et al. Remission induction in early rheumatoid arthritis with initial infliximab and methotrexate therapy: The course after infliximab discontinuation in the BeSt trial. Presented at: the American College of Rheumatology Meeting; November 14, 2006. Washington, DC. Abstract 658.