Elan and Biogen Idec's Tysabri

Monica Holmberg, PharmD
Published Online: Friday, June 1, 2007

Elan and Biogen Idec?s Tysabri
The monoclonal antibody natalizumab (Tysabri) has received approval from the FDA as monotherapy in the treatment of relapsing multiple sclerosis (MS).1 Na-talizumab is promoted for patients who did not respond to or did not tolerate other MS treatments.2 The agent is administered as a once-monthly 300-mg infusion. It is distributed by Elan Pharmaceuticals Inc and manufactured by Biogen Idec Inc.1,3 Three cases of progressive multi-focal leukoencephalopathy (PML) were reported during clinical trials; 2 of these cases were fatal.2 PML is an opportunistic viral infection that infects the brain, causing either death or disability. Natalizumab?s prescribing information carries a boxed warning about the risk of developing PML while using the product.4 As another preventive measure, the availability of na-talizumab is limited to patients, providers, and pharmacies that are registered with the TOUCH prescribing program.

To differentiate between MS symptoms and PML, patients should receive magnetic resonance imaging before treatment with natalizumab begins. Physical examinations should be performed at 3 and 6 months after the first natalizumab infusion and every 6 months afterward.1

Mechanism of Action
The exact mechanism of natalizumab is not fully known. MS lesions are thought to result when activated inflammatory cells cross the blood?brain barrier (BBB). When leukocytes cross the BBB, an interaction results between the adhesion molecules of the inflammatory cells and their counterreceptors on the walls of the vessels. Natalizumab, which binds to the surface of the leukocytes, may exert its activity by blocking the interaction of the inflammatory cells with the endothelial vessel cells.3

Clinical Trials
In a randomized, double-blind study of 942 patients, natalizumab was compared with placebo in patients who had not received interferon-beta or glatiramer acetate for at least 6 months prior to the study.3 After 2 years, the relative risk of sustained increase in disability in the natalizumab group was reduced by 42%.4 In a randomized, double-blind study of 1171 patients, natalizumab was compared with once-weekly treatment with interferon beta-1a. After 2 years, the relative risk reduction was determined to be 24%.3

Safety
Natalizumab should not be given to any patient with a known hypersensitivity to any of its ingredients or to any patient with active PML or a history of PML. Hypersensitivity reactions, including anaphylaxis, have occurred during the infusion. Should a reaction occur, the infusion should be stopped immediately, and natalizumab should not be given again.

Patients using natalizumab may be at a greater risk for developing infections. Patients should not take antineoplastic, immunosuppressant, or immunomodu-lating drugs while receiving natalizumab therapy. Natalizumab is not approved for use in patients <18 years old. Natalizumab is in Pregnancy Category C. In clinical trials, the most common side effects of natalizumab were infections, hypersensitivity, depression, and cholelithiasis.3

Patient Education
Patients using natalizumab should understand that it is effective in slowing the disability associated with MS and reducing the number of MS exacerbations; however, it will not cure MS. Any new health problems?especially changes in thoughts, eyesight, balance, or strength?should be reported immediately to a health care professional.

Pharmacists should educate patients to recognize hypersensitivity reactions, such as itching, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. These symptoms may occur during or after the infusion and should be reported to a nurse or physician right away. Patients should inform all their health care providers about their treatment with natalizumab.3

Dr. Holmberg is a pharmacist with Phoenix Children?s Hospital, Phoenix, Ariz.

References:

1.  FDA Approves Resumed Marketing of Tysabri Under a Special Distribution Program. Available at: www.fda.gov/bbs/topics/NEWS/2006/NEW01380.html. Accessed March 2007.

2. Companies Launch Marketing of Tysabri for Relapsing MS. Available at: www.nationalmssociety.org/site/PageServer?pagename=HOM_RES_tysabri. Accessed March 2007.

3. Tysabri Complete Prescribing Information. Available at: www.tysabri.com/tysbProject/tysb.portal?utm_content=NowAvailable&gclid=CIuik5n4kosCFRSRYAodx3xWRA. Accessed March 2007.

4. Important Drug Warning. Available at: www.tysabri.com/tysbProject/tysb.portal?utm_content=NowAvailable&gclid=CIuik5n4kosCFRSRYAodx3xWRA. Accessed March 2007.



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