RA Treatment Strategies
Clifton Bingham, M.D. - Jon Giles, M.D.
Abstract 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
AUTHORS: SM. Van Der Kooij, AE Van Der Bijl, CF Allaart, YPM Goekoop-Ruiterman, JK De Vries-Bouwstra, AH Gerards, ML Westedt,FC Breedveld, BAC Dijkmans.
BACKGROUND: As treatment paradigms in RA evolve to earlier aggressive therapy in many patients, one of the unanswered questions is whether after a period of “induction” therapy, some DMARDS may be tapered off to maintain a clinical (and radiographic) response. The concept of induction has been demonstrated in the COBRA study with many reports showing that more aggressive up front therapy with nonbiological DMARDS results in improved outcomes at 2 and 5 years even after the induction regimen is discontinued, supporting the idea of the window of opportunity. Several papers have been presented over the last few years concerning the BeST study which evaluated the effect of 4 different treatment regiments for patients with early RA (see; also). One of the treatment arms was infliximab (IFX) + MTX with a discontinuation of IFX allowed if disease activity was low and sustained. This presentation evaluated the group of patients from the BeST study in whom IFX was discontinued after an initial good clinical response on IFX and MTX.
METHODS: 120 patients were randomized to receive infliximab with MTX. The baseline characteristics of the group were DAS 4.3, 64% rheumatoid factor positive, 73% with erosive disease. Treatment was begun with IFX 3 mg/kg plus MTX 25 mg/week. If the DAS, calculated before each IFX infusion, was >2.4, IFX was increased (6, 7.5 and max. 10 mg/kg/8 weeks). If DAS was ≤2.4 for more than 6 months, IFX was tapered off followed by MTX tapering to 10 mg/week. In the 3rd year, if DAS was <1.6 for more than 6 months, MTX 10 mg/wk was further tapered off. If the DAS was >1.6, MTX 10 mg/week was restarted, then, if the DAS was >2.4, MTX was next increased to 25 mg/week, and finally IFX was restarted and increased if necessary. Baseline and 3-year radiographs were evaluated.
RESULTS: After 2 years, 67/120 patients (‘Responders’, 56%) had discontinued IFX and tapered MTX dosages to a mean 12.6 mg/week; 23/120 patients were on variable IFX dosages ('Continued Treatment') and 30 patients failed IFX+MTX and switched to other treatments. After 3 years (a median 26 months after IFX discontinuation) 61/67 (91%) of the 'Responders' (51% of all 120 patients) still had low disease of DAS ≤2.4, and of these, 16 (15% reported in presentation) were in remission (defined by DAS < 1.6) without any DMARDS; 45 were on MTX at mean dose 12 mg/week and 2 on sulfasalazine. Four patients who were initial 'Responders' had restarted IFX, a median 22.5 months after initial discontinuation. Of the 23 who 'Continued Treatment', 3 failed IFX+MTX therapy and switched to SSA, 3 stopped IFX after DAS ≤2.4 for ³ 6 months and 17 remained on IFX (mean dose 5.5 mg/kg) with MTX. Mean Sharp score progression after 3 years was less in responders (2.5 units) than in those on continued treatment (4.5) and those who were failures (6.2).
CONCLUSIONS: Three years after starting treatment with IFX and MTX, 53% of patients with early RA had discontinued IFX with persistent states of low disease activity defined as DAS ≤ 2.4. Of these patients, 27% remained in clinical remission after stopping all anti-rheumatic drugs, without showing further radiographic evidence of progressive joint damage. These findings indicate that initial treatment with MTX + IFX may alter the course of early RA.
EDITORIAL COMMENT: The BeST study in spite of its limitations continues to provide important information regarding the management of RA. Few studies have compared head to head different treatment strategies as this one. These results are very exciting in demonstrating that an aggressive induction regimen may allow later tapering of biological therapy and even of doses of methotrexate. Whether this is even more possible the earlier such a strategy is introduced remains to be seen. Comparison with the other arms and strategies is needed. As with the PROMT study above (see) the incorporation of objective measurement (in this case the DAS) to guide treatment changes, provides the ability for a more unbiased evaluation of different strategies. Studies that have used such approaches have in general all demonstrated good results lending credence to the recommendation to incorporate some form of objective assessments (and defined goals) of therapy in daily care of patients for management decisions.
