FRI0148
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. Hørslev-Petersen 1,*M. L. Hetland 2P. Junker 1J. Pødenphant 2T. Ellingsen 3P. Ahlquist 1H. Lindegaard 1A. Linauskas 3A. Schlemmer 3M. Y. Dam 3I. Hansen 3H. C. Horn 1A. Jørgensen 3S. B. Krintel 2J. Raun 1C. G. Ammitzbøll 3J. S. Johansen 2M. Østergaard 2K. Stengaard-Pedersen 3
1Rheumatology, University , Southern Denmark, 2Rheumatology, University , Copenhagen, 3Rheumatology, University , Aarhus, Denmark
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.
|
MTX+PLACEBO |
MTX+ADALIMUMAB |
P |
|
Number of patients included /completers |
91/80 |
89/81 |
- |
|
Methotrexate (mg/week) 12 months |
20 (7/25) |
20 (7.5/20) |
0.33 |
|
Triamcinolone (ml) cumulated 0-12 months |
7 (2/17.8) |
5.4 (1.8/16.6) |
0.084 |
|
DAS28(CRP) 1 month |
3.4 (1.8-5.9) |
2.6 (1.7-5.1) |
0.003 |
|
DAS28(CRP)≤2.6; 1 month |
29% |
48% |
0.010 |
|
∆DAS28 (CRP) 0-1 month |
-1.9 (-0.3/-3.8) |
-2.6 (-0.8/-4.7) |
0.0011 |
|
DAS28(CRP) 12 months |
2.6 (1.7/4.7) |
2.0 (1.7/5.2) |
0.0088 |
|
DAS28(CRP)≤2.6; 12 months |
49% |
74% |
0.0011 |
|
CDAI ≤ 2,8; 12 months |
41% |
61% |
0.011 |
|
SDAI ≤ 3.3; 12 months |
40% |
63% |
0.0028 |
|
ACR/EULAR (28 joints) remission; 12 months |
31% |
48% |
0.0241 |
|
ACR/EULAR (40 joints) remission; 12 months |
27% |
47% |
0.0098 |
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.
References: (1)Hetland et al: Arthritis Rheum 2006;54:1401-09. (2)Hetland et al: Ann Rheum Dis 2008;67:815-22.
Disclosure of Interest: K. Hørslev-Petersen Grant / Research support from: AbbottM. Hetland Grant / Research support from: Abbott, Bristol-Meyers Squibb, Roche, Schering-Plough/MSD, UCB-Nordic, and Wyeth/Pfizer Speakers Bureau: Abbott, Centocor, Roche,Schering-Plough/MSD, UCB-Nordic, and Wyeth/PfizerP. Junker: None DeclaredJ. Pødenphant: None DeclaredT. Ellingsen: None DeclaredP. Ahlquist: None DeclaredH. Lindegaard Speakers Bureau: RocheA. Linauskas: None DeclaredA. Schlemmer Speakers Bureau: MSD, RocheM. Dam: None DeclaredI. Hansen: None DeclaredH. Horn: None DeclaredA. Jørgensen: None DeclaredS. Krintel: None DeclaredJ. Raun: None DeclaredC. Ammitzbøll: None DeclaredJ. Johansen: None DeclaredM. Østergaard Grant / Research support from: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth. Speakers Bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth.K. Stengaard-Pedersen Grant / Research support from: Abbott