Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial

Emery, Paul; Breedveld, Ferdinand C.; Hall, Stephen; Durez, Patrick; Chang, David J.; Robertson, Deborah; Singh, Amitabh; Pedersen, Ronald; Koenig, Andrew; Freundlich, Bruce

doi:10.1016/s0140-6736(08)61000-4

Cited by 736 publications

(476 citation statements)

References 30 publications

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“…Furthermore, the DAS28 is a recommended remission outcome measure as stated by the European League Against Rheumatism (EULAR)/ACR collaborative recommendations for reporting disease activity (31). It remains an important primary outcome measure for clinical studies (14). It should also be noted that in the majority of cases the synovitis was subclinical, and examination of more joints or use of more stringent remission criteria would not have been associated with less imaging-detected synovitis (data not shown).…”

Section: Imaging-detected Synovitis In Remission After Two Treatmentmentioning

confidence: 99%

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease‐modifying antirheumatic drugs: A clinical and imaging comparative study

Saleem¹,

Brown²,

Keen³

et al. 2009

Arthritis & Rheumatism

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128

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Objective. For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis.Methods. One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n ‫؍‬ 50) or DMARDs (n ‫؍‬ 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1-5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity.Results. In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P ‫؍‬ 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission.Conclusion. In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in >48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis.Disease remission is the major goal for patients with rheumatoid arthritis (RA) (1).

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Section: Imaging-detected Synovitis In Remission After Two Treatmentmentioning

confidence: 99%

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease‐modifying antirheumatic drugs: A clinical and imaging comparative study

Saleem¹,

Brown²,

Keen³

et al. 2009

Arthritis & Rheumatism

Self Cite

128

View full text Add to dashboard Cite

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“…Tumor necrosis factor (TNF) is considered to be a major cytokine involved in RA pathogenesis, and anti-TNF therapy using monoclonal antibodies or fusion proteins was the first anti-cytokine therapy to be developed for RA [4–6]. Anti-TNF therapy has achieved great success in suppressing rheumatoid inflammation and preventing the progression of joint damage in RA patients [7–9], thereby confirming that TNF indeed appears to be critically involved in the pathogenesis of RA synovitis. However, TNF is not the only cytokine involved in RA pathogenesis, and several candidate cytokines represent potential therapeutic targets for anti-cytokine therapy.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

et al. 2010

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Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients.

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“…Finally, the Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis (COMET) trial tested methotrexate monotherapy versus methotrexate and etanercept in methotrexate-naïve RA patients with early moderate-to-severe disease of 3-24 months duration. 32 At 1 year, 50% of patients in the combination group achieved remission compared with 28% in the methotrexate alone group. Furthermore, 80% of patients in the combination group achieved radiographic nonprogression, compared with 59% in the methotrexate alone group.…”

Section: Medical Treatment Of Rheumatoid Arthritismentioning

confidence: 98%

Core Management Principles in Rheumatoid Arthritis to Help Guide Managed Care Professionals

Agarwal¹

2011

JMCP

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Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial

Cited by 736 publications

References 30 publications

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease‐modifying antirheumatic drugs: A clinical and imaging comparative study

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease‐modifying antirheumatic drugs: A clinical and imaging comparative study

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

Core Management Principles in Rheumatoid Arthritis to Help Guide Managed Care Professionals

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