Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Adalimumab Added to Methotrexate and Intra-Articular Glucocorticoid Increases Remission Rates At One Year In Early, DMARD-Nave Patients with Rheumatoid ArthritisAn Investigator-Initiated Randomized, Controlled, Double-Blinded Study.

Horslev-Petersen1,  Kim, Hetland2,  Merete L., Junker3,  Peter, Podenphant4,  Jan, Ellingsen5,  Torkell, Ahlqvist6,  Palle, Lindegaard3,  Hanne M.

University of Southern Denmark, Graasten, Denmark
Viborg Hospital, Viborg, Denmark
Copenhagen University Hospital at Glostrup, Copenhagen, Denmark
Copenhagen University Hospital at Glostrup, Glostrup, Denmark
Odense University Hospital, Odense C, Denmark
Copenhagen University at Gentofte,, Hellerup, Denmark
University Hospital, Silkeborg, Denmark
Vejle Hospital,, Vejle, Denmark
Vendsyssel Hospital, Hjørring, Denmark
Aalborg Hospital, Aalborg, Denmark
Arhus University Hospital, Aarhus, Denmark

Background/Purpose:

To assess efficacy and safety, including remission rates by adding adalimumab (ADA) to methotrexate (MTX) and intra-articular glucocorticoid (triamcinolone) in patients with early DMARD-naïve rheumatoid arthritis (RA) fulfilling the ACR 1987 criteria.

Methods:

DMARD naive RA patients with disease duration < 6 months (n=180) were randomized 1:1 to MTX 7.5 mg weekly + ADA 40 mg (ADA) every other week or MTX + placebo (PLA). At week 0, 4, 8, and 12 followed by every 3rd month up to 12 months, patients had triamcinolone injections into swollen joints (max 4 joints or max 4ml/visit). In addition the patients were contacted fortnightly during the first 3 months and monthly thereafter. If disease activity was suspected, an extra visit was scheduled and swollen joints were injected. MTX was increased to 20 mg/week within two months. If persisting DAS28(CRP)>3.2 after three months, sulphasalazine 2g/day and hydroxychloroquine 200mg/day were added. Patients with persistent DAS28(CRP)>3.2 in spite of triple therapy were excluded and started rescue biologic medication. NSAID, muscle relaxants, or medium or strong analgesics were not allowed. Clinical response was assessed according to DAS28(CRP), SDAI and ACR/EULAR remission criteria. Primary analysis was by ITT with last observation carried forward. Completer analysis and ITT without imputations were also performed and gave similar results (not shown). Differences between groups were tested by Mann-Whitney or by Pearson's chi-square test.

Results:

At baseline no significant differences were seen between MTX+PLA and MTX+ADA: 69%/63% were women, median age was 54.4/56.2 years, disease duration 83/84 days, anti-CCP positive 70%/60%, IgM-RF positive 74%/70%, DAS28(CRP) 5.4/5.3, tender joint count (40) 16/15, swollen joint count (40) 11/10, patient's VAS pain 58/63mm and fatigue 54/67mm, doctor's VAS global 51/57mm, HAQ 1.0/1.1. Data for MTX after 12 months and use of triamcinolone 0–12 months are presented in the table. Triple therapy was added in 25/17 patients (p=0.25). 80/81 patients completed the study. 2/4 patients started rescue biologic medication. Serious adverse advents were reported in 13 patients, including three with malignancies (urothelial, lung and non-melanoma skin cancer). The frequency of DAS28(CRP)<3.2 (primary outcome) did not differ significantly between the groups, but in the MTX+ADA group significantly more patients achieved clinical remission (DAS28, SDAI and ACR/EULAR remissions) at 12 months (secondary outcome) (table).

 MTX+PLAMTX+ADAp
Number of patients9189
Methotrexate (mg/week) 12 months20 (7/25)20 (7.5/20)0.33
Triamcinolone (ml) 0 – 12 months7 (2/17.8)5.4 (1.8/16.6)0.084
DAS28 (CRP) 12 months2.2 (1.3/4.5)1.7 (1.2/5.2)0.0007
DDAS28 (CRP) 0–12 months-3.0 (-0.2/-5.0)-3.2 (-0.2/-5.7)0.11
DAS28 (CRP)<3.2; 12 months81%84%0.74
DAS28 (CRP)<2.6; 12 months49%74%0.0011
SDAI <= 3.3; 12 months40%63%0.0028
ACR/EULAR (28 joints) remission; 12 months31%48%0.0241
ACR/EULAR (40 joints) remission; 12 months27%47%0.0098
Values are medians(5%/95% percentiles) unless otherwise stated (%).

Conclusion:

In DMARD naïve patients with early RA, excellent disease control was achieved by a targeted step-up strategy using methotrexate and intra-articular glucocorticoid injections. Addition of adalimumab to methotrexate and intra-articular glucocorticoid improved the remission rates considerably. The treatments were well tolerated.

To cite this abstract, please use the following information:
Horslev-Petersen, Kim, Hetland, Merete L., Junker, Peter, Podenphant, Jan, Ellingsen, Torkell, Ahlqvist, Palle, et al; Adalimumab Added to Methotrexate and Intra-Articular Glucocorticoid Increases Remission Rates At One Year In Early, DMARD-Nave Patients with Rheumatoid ArthritisAn Investigator-Initiated Randomized, Controlled, Double-Blinded Study. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :394
DOI:

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