A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis

Bathon, Joan M.; Martin, Richard W.; Fleischmann, Roy; Tesser, John; Schiff, Michael; Keystone, Edward; Genovese, Mark C.; Wasko, Mary Chester; Moreland, Larry W.; Weaver, Arthur L.; Markenson, Joseph A.; Finck, Barbara

doi:10.1056/nejm200011303432201

Cited by 1,604 publications

(1,020 citation statements)

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“…Both methotrexate and etanercept have been demonstrated to reduce radiographic progression in RA (13,21). Improvement in radiographic progression may lead to further long-term benefits such as a reduction in joint arthroplasty and improved physical function.…”

Section: Discussionmentioning

confidence: 99%

“…Newer data suggest that radiographic evidence of joint damage is apparent even in patients with very early disease (11)(12)(13)(14)(15). Therefore, it is important to consider implementation of diseasemodifying drugs at earlier stages of disease.…”

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confidence: 99%

“…Therefore, it is important to consider implementation of diseasemodifying drugs at earlier stages of disease. In addition, it has been shown that despite treatment with traditional DMARDs, patients with persistent disease continue to deteriorate radiographically and lose functional capacity (13)(14)(15). This finding is especially important considering that studies have demonstrated a direct correlation between declining functional status and increased rates of morbidity and mortality (16)(17)(18)(19)(20).…”

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confidence: 99%

“…This finding is especially important considering that studies have demonstrated a direct correlation between declining functional status and increased rates of morbidity and mortality (16)(17)(18)(19)(20). Previous studies have shown that both methotrexate and etanercept (Enbrel; Immunex, Seattle, WA) have the ability to slow radiographic progression in addition to providing positive effects on functional status (13,21). Therefore, the combination of etanercept plus methotrexate may be an important and beneficial treatment modality for patients with RA.…”

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confidence: 99%

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Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

Kremer¹,

Weinblatt²,

Bankhurst³

et al. 2003

Arthritis & Rheumatism

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Objective. To observe the long-term safety and efficacy of combination therapy with etanercept and methotrexate in patients with rheumatoid arthritis (RA), and to determine whether the addition of etanercept allowed reductions in methotrexate or corticosteroid dosages while maintaining a clinical response.Methods. Patients with RA who received methotrexate plus etanercept in a previous randomized, placebo-controlled trial were offered the opportunity to enroll in an open-label extension study for further evaluation of treatment with etanercept and methotrexate.Results. Seventy-nine of the 89 patients in the original blinded study enrolled in the extension study, and 65 of these patients continue in the study. Patients have received etanercept therapy for up to 47 months (median 44 months). The types and rate of adverse events noted during the extension trial were similar to those observed in the controlled trial. At the 3-year assessment, 77% of the 57 patients available for evaluation met American College of Rheumatology 20% (ACR20) criteria for improvement in RA, 47% met the ACR50 criteria, and 23% met the ACR70 criteria. Of the 36 patients assessed at 3 years in the extension study, 30 (83%) were able to decrease their dosages of corticosteroids, and 20 (56%) were able to discontinue corticosteroid therapy. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).Conclusion. In this observational continuation study, the addition of etanercept to background methotrexate provided sustained clinical benefit over a median period of 44 months. With etanercept therapy, there were trends toward dosage reduction or discontinuation of methotrexate and corticosteroids, without apparent worsening of ACR response rates. Compared with the controlled trial, no increases in the rate of adverse events were observed.Over the past several decades, methotrexate has become increasingly recognized among rheumatologists as the gold standard in treating patients with rheumatoid arthritis (RA) (1,2). Compared with other, more traditional disease-modifying antirheumatic drugs (DMARDs), methotrexate has a more rapid onset of action, superior long-term effectiveness, and fewer cumulative toxicities (3-6). Studies show that 80% of patients discontinue other DMARDs after 2 years, while at least 50% continue to take methotrexate for Ͼ5 years (7-9). However, despite its advantages over traditional agents, methotrexate is associated with toxicity, and Supported by Immunex Corporation, Seattle, Washington (study drug and grants to the investigational sites).

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Section: Discussionmentioning

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Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

Kremer¹,

Weinblatt²,

Bankhurst³

et al. 2003

Arthritis & Rheumatism

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“…Cytochrome C that has leaked out of the mitochondria forms a complex (the "apoptosome") with Apaf-1 and caspase 9, which is able to activate caspase 3. anti-inflammatory effects of 2 TNF-␣-neutralizing antibodies, infliximab and CDP571, 8,12 observed in a very similar population of patients with active Crohn's disease. Because etanercept has potent anti-inflammatory effects in rheumatoid arthritis, 13,14 the mechanisms of the therapeutic efficacy of TNF-binding molecules in Crohn's disease and rheumatoid arthritis seem to differ. Lü gering et al 11 have studied the effects of infliximab, a high-affinity TNF-␣-binding mouse/human chimeric antibody, on circulating monocytes from patients with active Crohn's disease, and showed that a significant fraction of these cells died from apoptosis.…”

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Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease

Deventer

2001

Gastroenterology

113

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Risk of Malignancies in Patients With Rheumatoid Arthritis Treated With Biologic Therapy

López-Olivo

Tayar

Martínez-López

et al. 2012

JAMA

282

147

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A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis

Abstract: As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.

Cited by 1,604 publications

References 22 publications

Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease

Risk of Malignancies in Patients With Rheumatoid Arthritis Treated With Biologic Therapy

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