Remission rates increase substantially by adding adalimumab to methotrexate and intra-articular glucocorticoid in patients with early rheumatoid arthritis-1-year results of investigator-initiated, double-blinded randomized clinical trial (OPERA)K. Hoørslev-Petersen1

Background In the CIMESTRA Study patients with early rheumatoid arthritis (RA) were treated with methotrexate (MTX) and intra-articular glucocorticoid. This led to results comparable to biological trials with 34%/28% of pts in DAS28/ACR remission after 1 year (1,2). Objectives We studied if addition of adalimumab (ADA) to the CIMESTRA strategy is of further therapeutic benefit. Methods DMARD naïve early RA patients with disease duration <6 months (n=180) were randomized 1:1 to MTX 7.5 mg weekly + ADA 40 mg eow or MTX + placeboADA (PLA). MTX was increased to 20 mg/week within two months. Treatment target was low disease activity (DAS28(CRP) <3.2). Injections of triamcinolone were given into swollen joints (max. 4 joints/4 ml/visit). Oral prednisolone was not allowed. Sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added if DAS28(CRP) >3.2 after three months. Efficacy was assessed by DAS28(CRP), CDAI, SDAI and ACR/EULAR Boolean remission criteria. Primary analysis was by ITT with last observation carried forward. Completer analysis and ITT without imputations gave similar results (not shown). Values are medians (5%/95% percentiles) or percentage. We used Mann-Whitney or Pearson's chi-square tests. Results Baseline characteristics were similar between MTX+PLA/MTX+ADA groups: Women: 69%/63%; age: 54.4/56.2 years; disease duration: 83/84 days; anti-CCP positive: 70%/60%; IgM-RF positive: 74%/70%; DAS28(CRP): 5.6/5.5;

HAQ:

1.0/1.1 (all NS). Triple therapy was added in 25/17 patients (p=0.25). Treatment target was reached in 46%/58% (MTX+PLA/MTX+ADA) at 1 month, 63%/73% (2 months), 70%/76% (3 months), and 76%/80% (12 months) (NS between groups at all time points). However, in the MTX+ADA group significantly more patients achieved rapid and sustained clinical remission as assessed by DAS28, CDAI, SDAI and ACR/EULAR remission criteria (table). Number needed to treat (NNT) with ADA to achieve remission in one extra patient at 1 year was 4 to 5.9 depending on remission criteria. (Table Presented) Conclusions Low disease activity was achieved by $≈ $80% in both groups, but remission rates increased considerably by adding adalimumab to methotrexate and intraarticular glucocorticoid injections in DMARD naïve patients with early RA.