Early, Aggressive Combination Rx May Alter the Course of RA

Disease Remission Seen in Some Patients at 3-Year Follow-Up

WASHINGTON, DC?Initial treatment with methotrexate (Rheumatrex, Trexall) and infliximab (Remicade) early in the course of rheumatoid arthritis (RA) can lead to remission in some patients, according to new data presented at the American College of Rheumatology annual meeting. Whether remission can last long-term without the combination therapy has not been determined.

"These 3-year follow-up results indicate that initial treatment with methotrexate and infliximab may alter the course of early rheumatoid arthritis and, in many cases, move patients into remission," said coinvestigator Sjoerd van der Kooij, MD, of Leiden University Medical Center, the Netherlands.

This Dutch study referred to as BeSt ("Behandel Strategie?n," ie, Treatment Strategies) included 508 patients with early evidence of RA (mean age, 54 years; 68% women).

Four treatment strategies were evaluated, using various combinations of disease-modifying antirheumatic drugs (DMARDs), along with the tumor necrosis factor (TNF)-a antagonist infliximab and other agents:

Group 1

? (n = 126): Sequential monotherapy starting with methotrexate, then sulfasalazine (Azulfidine), then leflunomide (Arava), then methotrexate plus infliximab for 8 weeks

Group 2

? (n = 121): Step-up combination therapy, starting with methotrexate, then adding sulfasalazine, hydroxychloroquine sulfate (Plaquenil), and finally prednisone (eg, Deltasone, Meticorten), before switching to methotrexate plus infliximab

Group 3

? (n = 128): Initial combination therapy with methotrexate, sulfasalazine, and prednisone, then methotrexate with cyclosporine (eg, Gengraf, Neoral) and prednisone, then methotrexate plus infliximab

Group 4

? (n = 128): Initial combination therapy with methotrexate plus infliximab, then sulfasalazine, then leflunomide, then methotrexate with cyclosporine and prednisone.

All patients who started infliximab therapy also received methotrexate. The small number of patients who discontinued methotrexate because of adverse events were switched to an alternative DMARD (usually sulfasalazine).

The use of initial combination therapies was superior to the use of initial monotherapy in producing early improvements in functional ability, as well as in reducing radiographic evidence of joint damage

progression.

After 2 years of treatment, 56% of patients initially treated with the combination of methotrexate and infliximab were able to discontinue infliximab without relapse and to gradually taper methotrexate down to 10 mg/week.

After 3 years of initial treatment, 15% of the patients in group 4?who began treatment with methotrexate plus infliximab?were able to taper off infliximab. They have remained in remission, with no measurable signs of RA disease activity.

Only 4 of the original 67 patients who were taking methotrexate 10 mg/week at 2 years needed to increase the dose to 25 mg/week and restart infliximab during the third year, because of a flare in disease activity.

This study is the only large cohort trial of patients with early RA in which participants have successfully discontinued infliximab after reaching a low level of disease activity.

Thomas Huizinga, MD, professor of rheumatology at Leiden Medical Center who oversaw the study, said these findings should change the way physicians think about RA. Until now, it was thought that disease progression was unavoidable in a large percentage of patients with RA, regardless of medical management.

IMWR

"Our findings are something that had never been seen before. Until now, it was basically a wait-and-see policy," Dr Huizinga told . "This combination may mean a lot less pain and overall morbidity among patients who are treated early."

"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," said Dr van der Kooij.

Key points

? RA has been traditionally considered an unrelentingly progressive disease.

? New data show that early, intensive combination therapy can lead to remission in some patients.

? Early initial therapy with a DMARD plus a TNF-α antagonist is more effective than DMARD monotherapy.

? In this study, 15% of patients with early RA who started therapy with methotrexate plus infliximab had no signs of disease activity at 3 years.