Rheumatoid Arthritis Patients Benefit From Enbrel In Combination With Methotrexate

Rheumatoid arthritis patients who are on standard methotrexate therapy may benefit from the addition of the biologic treatment, Enbrel* (etanercept), according to new data from a one-year, open-label extension of the international TEMPO trial. The study results, presented this week at the European League Against Rheumatism (EULAR), 2006, also showed that the safety profile and clinical efficacy of Enbrel and methotrexate combination therapy were sustained at four years of treatment.1


The TEMPO extension trial was an open-label 52-week study involving subjects who had completed the 3-year double-blind TEMPO trial. At the end of the 3-year TEMPO trial, 227 subjects who met the specific predefined criteria continued into the 1-year, open-label extension. All subjects received treatment with the combination of Enbrel and methotrexate. Subjects receiving methotrexate monotherapy during the 3-year double-blind TEMPO trial were switched to the combination of Enbrel and methotrexate (n = 55). Subjects receiving Enbrel monotherapy during the 3-year double-blind TEMPO trial were switched to the combination of Enbrel and methotrexate (n = 76). Subjects receiving combination therapy during the 3-year double-blind TEMPO trial were continued on the same regimen (n = 96).


Commenting on the implications of the results, Professor Robert Moots, Professor of Rheumatology at the University of the Liverpool said: "These latest data show for the first time that the efficacy of combination treatment with methotrexate and Enbrel can be sustained for up to four years. This is encouraging news for rheumatoid arthritis patients who are currently on this regimen, or for patients who are discussing potential treatment choices with their consultant."


The results of the 227 patient one-year open-label extension of the TEMPO study show that the combination therapy with ENBREL and methotrexate demonstrated clinical improvement and was well-tolerated during the one-year study.1 Fifty per cent of patients taking ENBREL and methotrexate for four years achieved clinical remission based on the disease activity score (DAS)* of less than 1.6, the primary clinical efficacy endpoint, compared with 38.7 per cent at three years.1 Seventy-four per cent of patients taking ENBREL and methotrexate for four years achieved a DAS of less than 2.4 (low disease activity) compared with 66.7 per cent at three years.1 In addition, the data also demonstrate that among the rheumatoid arthritis patients treated with methotrexate monotherapy for three years, whose mean disease activity was moderate, the addition of ENBREL provided further improvement in clinical efficacy that approached the response achieved by patients treated with combination therapy for four years (mean DAS 1.9 vs. 1.8, respectively).1 The addition of methotrexate to patients who received ENBREL monotherapy for three years also resulted in improvements at four years (mean DAS 2.2)1. The proportions of subjects achieving clinical remission by adding ENBREL to methotrexate and adding methotrexate to ENBREL at four years were 41.8% and 38.2% and were not statistically different from each other nor compared to the combination group.1















Ailsa Bosworth, chief executive, National Rheumatoid Arthritis Society, UK said, "Rheumatoid arthritis is a painful and debilitating disease that has consequences not only for people with the condition but also for their families, friends and employers. It is vital that people with rheumatoid arthritis have access to treatments that have been proven effective to inhibit the progression of joint damage and to improve physical function."


Although there have been a relatively small number of studies reporting on prevalence, these studies show that rheumatoid arthritis affects approximately 0.5 to one per cent of the adult population in developed populations, and about twice as many women as men suffer from the disease.2 Patients with rheumatoid arthritis experience inflammation, and morning stiffness, usually in the small joints of the hands and feet and often symmetrically. As the disease progresses, irreversible joint damage may lead to limited motion and loss of function. Rheumatoid arthritis can be a devastating disease that can negatively affect quality of life and may result in increased feelings of depression. During the first three years of the disease, 20 to 30 per cent of patients become permanently work disabled. Within 10 years of diagnosis, almost 50 per cent of patients are unable to work.


*DAS


DAS is a combined index to measure disease activity in rheumatoid arthritis patients and is a validated tool used in clinical trials and serves as the basis for the EULAR response criteria.


ENBREL


In the European Union, Enbrel is approved alone or in combination with methotrexate for the treatment of active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrexate (unless contraindicated), has been inadequate. Enbrel is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. In patients with rheumatoid arthritis, Enbrel used alone or in combination with methotrexate has been shown to slow the progression of disease-associated structural damage as measured by X-ray .


Enbrel is given by injection and the recommended dosing is 25 mg twice weekly for all adult rheumatology indications8.


Since the product was first introduced, serious infections, some involving death, have been reported in patients using Enbrel. Patients should tell their doctor if they currently have an infection or are prone to getting infections. Patients should not start Enbrel if they have an infection of any type or an allergy to Enbrel or its components. Enbrel should be used with caution in patients prone to infection8.


The most frequent adverse event in clinical trials in rheumatoid arthritis patients were injection-site reactions (ISRs) (36%)8.


Enbrel acts by binding tumor necrosis factor (TNF), one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory processes of rheumatoid arthritis. The binding of Enbrel to TNF renders the bound TNF biologically inactive, which can result in reduction of inflammatory activity8.


WYETH


Wyeth Pharmaceuticals, a division of Wyeth (NYSE:WYE), has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, transplantation, haemophilia, oncology, vaccines and nutritional products. Wyeth has a diverse portfolio of biopharmaceutical products and is currently marketing seven of these products. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.


CSR-64179 An open-label, multicentre, extension study of the combination of etanercept and methotrexate in rheumatoid arthritis subjects. 11 May 2006

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Enbrel (etanercept) SmPC. Last updated 21 September 2005. Accessed from Electronic Medicines Consortium (accessed 19 June 2006)


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