Early Aggressive Treatment May Alter Course Of Rheumatoid Arthritis

Early administration of methotrexate and infliximab may lead to remission in patients with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.


Methotrexate and the injectable infliximab are among several disease-modifying antirheumatic drugs administered to reduce or prevent joint damage as well as preserve joint integrity. These drugs, often used in conjunction with non-steroidal anti-inflammatory drugs like ibuprofen, have greatly improved symptoms, function and quality of life for patients with rheumatoid arthritis.


Dutch rheumatologists, conducting a long-term BeSt ("Behandel Strategie?n" or "Treatment Strategies") study on 508 patients with early evidence of the rheumatoid arthritis, explored four strategies for treatment utilizing various combinations of these DMARDS. These strategies included: sequential monotherapy, monotherapy building up to combination therapy, and initial combination therapy using either prednisone or infliximab. All patients who started infliximab also were on methotrexate. In the case of adverse drug events requiring the discontinuation of methotrexate, an alternative DMARD (usually sulfasalazine) was started in combination with infliximab.


The initial combination therapies proved superior to initial monotherapy in gaining earlier improvement in functional ability and decreasing radiographic joint damage progression. After two years, 56% of patients treated with the initial combination of methotrexate and infliximab were able to discontinue infliximab without relapse, and subsequently taper methotrexate to 10 mg/week. A year later, 14% of all patients receiving initial treatment with infliximab tapered off all medication and are still in remission (no measurable signs of disease activity). Only four patients (out of the original 67 responders at two years) who were on methotrexate 10 mg/week had to increase methotrexate to 25 mg/week and restart infliximab during the third year because of a flare in disease activity.


Currently, the BeSt study includes the only large cohort of patients with early rheumatoid arthritis who have successfully discontinued infliximab after achieving low disease activity. Given many patients' ability to achieve remission after two years and taper medication to methotrexate 10 mg/week, BeSt researchers had added the goal of discontinuation to third-year follow-up.


"These three-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," summarizes Sjoerd van der Kooij, MD, Leiden University Medical Center, Leiden, The Netherlands, an investigator in the study. "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."















The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.


Presentation Number: 658


Remission Induction in Early Rheumatoid Arthritis (RA) with Initial Infliximab (IFX) and Methotrexate (MTX) Therapy: The Disease Course After IFX Discontinuation in The BeSt Trial


S. M. Van Der Kooij1, A. E. Van Der Bijl1, C. F. Allaart1, Y. P.M. Goekoop-Ruiterman1, J. K. De Vries-Bouwstra2, A. H. Gerards3, M. L. Westedt4, F. C. Breedveld1, B. A.C. Dijkmans2. 1LUMC, Leiden, The Netherlands; 2VUMC, Amsterdam, The Netherlands; 3Vlietland, Schiedam, The Netherlands; 4Bronovo, The Hague, The Netherlands


PURPOSE


To describe the clinical and radiological outcome of patients with early RA who discontinued IFX after good clinical response on initial treatment with IFX+MTX.


METHODS


In the BeSt study, a randomized clinical trial comparing 4 different treatment strategies in early RA, 120 patients in Group 4 (baseline DAS 4.3, 64% rheumatoid factor positive, 73% erosive) started treatment with IFX 3 mg/kg plus MTX 25 mg/week. If the DAS, calculated 1-2 weeks before each IFX infusion, was >2.4, IFX was increased (6, 7.5 and max. 10 mg/kg/8 weeks). If DAS was == 6 months, IFX was tapered to nil and next MTX was tapered to 10 mg/week. In the 3rd year, if DAS was = 6 months, MTX 10 mg/wk was tapered to nil. If the next DAS was >1.6, MTX 10 mg/week was restarted, then, if the DAS was >2.4, first MTX was increased to 25 mg/week, next IFX was restarted and if necessary increased. Baseline and 3-year Sharp-van der Heijde Scores (SHS) were assessed independently in random order by 2 physicians.


RESULT


After 2 years, 67/120 patients ('Responders', 56%) had successfully discontinued IFX and tapered MTX to (mean) 12.6 mg/week; 23/120 patients were on variable IFX dosages ('Continued Treatment') and 30 patients had failed on IFX+MTX and switched to other treatment steps.


After 3 years, median 26 months after IFX discontinuation, 61/67 (91%) of the 'Responders' (51% of all 120 patients) still had DAS =