AMSTERDAM — Early and aggressive therapy with infliximab and methotrexate may favorably alter the course of rheumatoid arthritis, according to new data from the Dutch BEST trial.
After 3 years of follow-up, 55% of the 120 BEST participants initially randomized to combined therapy with infliximab and methotrexate were able to wean off infliximab because they were able to maintain persistently low disease activity without the tumor necrosis factor inhibitor. They had discontinued infliximab a median of 26 weeks earlier, thereafter consistently maintaining a Disease Activity Score (DAS) of 2.4 or less, down from a mean baseline DAS of 4.3, Dr. Arie E. van der Bijl reported at the annual European Congress of Rheumatology.
After discontinuing infliximab, most of these patients remained on methotrexate maintenance monotherapy at a mean dose of 12 mg/week.
Of particular note was the finding that 17 patients, or 14% of the original 120, were in clinical remission as defined by a DAS of 1.6 or less without any antirheumatic drugs.
“These results support the possibility that a window of opportunity may exist in which the character of rheumatic inflammation could be altered by early intense therapy,” declared Dr. van der Bijl of Leiden University Medical Center, the Netherlands.
BEST is a multicenter randomized trial comparing four different treatment strategies in 506 patients with early rheumatoid arthritis (RA).
Dr. van der Bijl's third-year update of the trial focused on the study arm involving infliximab and methotrexate combination therapy.
Although several members of the audience speculated that similarly favorable 3-year results might have been achieved with early methotrexate monotherapy, which is known to produce very good outcomes in a minority of RA patients, Dr. van der Bijl was quick to correct them on that score.
Another of the four BEST study arms featured exactly that strategy, and the results in terms of rates of low disease activity or clinical remission were not nearly as good as in the combined infliximab/methotrexate arm.
The new BEST results, while encouraging, warrant cautious interpretation. Whether early infliximab plus methotrexate truly alters the course of rheumatoid arthritis must await longer-term follow-up, including, most importantly, radiologic evidence of prevention of progressive joint damage, the rheumatologist stressed.
BEST participants had a median symptom duration of 23 weeks at the time of enrollment in the trial. At baseline, two-thirds were rheumatoid factor-positive and three-quarters had joint erosions.
Patients initially received infliximab at 3 mg/kg every 8 weeks plus methotrexate at 25 mg/week. If their DAS remained above 2.4, the infliximab dose was bumped up to 6 mg/kg, then if necessary 7.5 and finally 10 mg/kg every 8 weeks.
When the DAS dropped below 2.4 for 6 consecutive months, infliximab was tapered and, if possible, stopped.
After 2 years, 18% of patients were determined to be infliximab/methotrexate treatment failures and were switched to sulfasalazine.
At the 2-year mark, 77 patients had discontinued infliximab because of a good clinical response; however, 10 of them had to restart the biologic agent after a mean of 2.1 months because of a disease flare. Of the remaining 67 good responders, only 4 had to restart infliximab during year 3 because of a disease flare.
Dr. van der Bijl accepted a EULAR/Abbott Award honoring the BEST report as one of the top six clinical studies presented at the annual congress.
BEST is supported by the Dutch government and the Dutch College of Health Insurance Companies.
A window of opportunity may exist for early intense therapy to alter the character of rheumatic inflammation. DR. VAN DER BIJL