Etanercept

Etanercept is an injectable drug that blocks the action of tumor necrosis factor-alpha (TNF-alpha); it is a large molecule made by combining two proteins made by recombinant DNA technology. Etanercept has several approved and off-label uses for a variety of immune-modulated and inflammatory diseases. In North America, Amgen and Wyeth co-market the drug as Enbrel; in the rest of the world, Wyeth markets the drug. It is sold as either a dry powder or a pre-mixed liquid and was approved for use in 1998.

Uses

The approved indications for etanercept include:

• Moderate to severe rheumatoid arthritis
• Moderate to severe polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Moderate to severe plaque psoriasis

Etanercept may be appropriate for several additional diseases despite the lack of governmental approval. Diseases with well-established roles for TNF-alpha include granulomatous diseases, neutrophilic dermatoses, vasculitis, and graft versus host disease. Other diseases where etanercept has been used include Alzheimer disease^[1]. Etanercept has also been included in efforts to improve the outcomes of islet transplantation as a cure for type 1 diabetes.^[2] The drug may also be useful in eye disorders caused by inflammation such as ^[3]

How Etanercept Is Taken

Etanercept is supplied as either 25 mg powder in a vial or 50 mg drug in a pre-filled syringe. Etanercept must be injected; if it were swallowed it would be destroyed by the digestive system. When it is supplied as a dry powder, it must be mixed with liquid before injection. The recommended dose is 50 mg per week, given by subcutaneous injection; the total dose can be given once a week, or smaller (25 mg) doses can be given twice a week.

How It Works

Etanercept works by binding to the powerful inflammatory mediator TNF-alpha, thereby decreasing the inflammation caused by high TNF-alpha levels in a variety of diseases.

Benefits

Etanercept has provided significant benefits and dramatically improved the quality of life of many patients. In psoriatic arthritis, all three drugs that block TNF-alpha were significantly more effective than placebo on the basis of Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology response criteria ACR20, ACR50, and ACR70 ratings.^[4]

Risks and Precautions

Because etanercept alters the function of the immune system, infections are an expected risk of therapy. Serious infections leading to hospitalization or death have been reported in patients treated with etanercept; infections have included bacterial sepsis and tuberculosis. In addition, some patients experience injection site reactions, which were generally not severe enough to discontinue taking the drug; the reactions included pain, itching, swelling, or redness at the site of the injection. Reports of bleeding or bruising after injection have also been made.

Another potential consequence of inhibiting the immune system is an increased incidence of certain types of cancer. With etanercept, an increased rate of hematologic malignancies (leukemias and lymphomas) has been noted.^[5]

History

The discovery of how TNF was identified as a key player in inflammatory and immune-related diseases that eventually led to targeted drugs is one of dedicated and focused basic research that led to the Lasker Award in 2003.^[6] Once TNF-alpha was firmly established as a causative agent in inflammatory diseases, efforts to block the molecule began in earnest. Etanercept is one of several drugs that target TNF-alpha and was initially developed at Immunex, a biotechnology company that was acquired by Amgen in 2002.

Alternatives

Other drugs share etanercept's mechanism of action.

• Infliximab (Remicade) is a chimeric monoclonal antibody with parts derived from both mouse and human parent molecules.
• Adalimumab (Humira) is the newest of the anti-TNF drugs; it is a fully human monoclonal antibody that is specific for TNF-alpha.

References

1. ↑ Tobinick E. Perispinal etanercept for treatment of Alzheimer's disease. Curr Alzheimer Res. 2007 Dec;4(5):550-2. Abstract
2. ↑ Faradji RN, Tharavanij T, Messinger S, et al. Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept. Transplantation. 2008 Dec 27;86(12):1658-65. Abstract
3. ↑ Rodrigues EB, Farah ME, Maia M, et al. Therapeutic monoclonal antibodies in ophthalmology. Prog Retin Eye Res. 2008 Dec 10. Abstract
4. ↑ Saad AA, Symmons DP, Noyce PR, Ashcroft DM. Risks and benefits of tumor necrosis factor-alpha inhibitors in the management of psoriatic arthritis: systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2008 May;35(5):883-90. Abstract
5. ↑ Nair B, Raval G, Mehta P. TNF-alpha inhibitor etanercept and hematologic malignancies: report of a case and review of the literature. Am J Hematol. 2007 Nov;82(11):1022-4. Abstract | PDF
6. ↑ Feldmann M, Maini RN. Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med. 2003 Oct;9(10):1245-50. Abstract | Full Text | PDF