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Medications that slow or stop the progression of multiple sclerosis (MS) are difficult to come by?so difficult, in fact, that only 5 other such disease-modifying agents were available in the United States when the FDA licensed Biogen Idec and Elan's natalizumab (Tysabri) in November 2004 (Table 1).1
The FDA had moved quickly on Tysabri after receiving preliminary data from placebo-controlled clinical trials showing that the new biologic was very effective and generally well-tolerated when used alone or in combination with Biogen Idec's interferon beta-1a (Avonex). Any excitement or changes in MS treatment that Tysabri's introduction may have generated were quickly muted, however.
Biogen Idec and Elan voluntarily withdrew Tysabri from the market on February 28, 2005, when the rare opportunistic infectious disease progressive multifocal leukoencephalopathy (PML) was reported in 2 MS patients receiving the drug. Tysabri dosing in ongoing studies also was suspended at that time, but a third case of PML was found in a participant in a Crohn's disease trial.2
Following an extensive review of adverse events with Tysabri and the publication of 2-year data from MS treatment studies, the FDA relicensed the medication in July 2006 with a narrowed indication and a strict risk management program.
A TOUCH of Infection Prevention
Key to the reintroduction of Tysabri was Biogen Idec and Elan's collaborating with the FDA to develop the Tysabri Outreach: Unified Commitment to Health (TOUCH) prescribing program. This program is designed primarily to minimize patients' risk for PML, but it also will facilitate the tracking of all adverse events associated with the use of Tysabri.
PML is caused by the typically harmless JC virus and is marked by clumsiness, progressive weakness, and visual, speech, and sometimes personality changes. There is no treatment, and PML nearly always is fatal.
Any pharmacist, pharmacy, prescriber, wholesaler, or patient involved in the distribution or administration of Tysabri must register with TOUCH and complete educational and reporting requirements. Patients taking Tysabri must be given a Medication Guide each time they receive an infusion.
For now, Tysabri will be available only through 13 specialty pharmacies (Table 2). A Web site (www.tysabri.com), call center (800-456-2255), pregnancy registry, 5-year postmarketing safety study, and ongoing TOUCH evaluation also are elements of Tysabri's risk management program.
Tysabri is the first selective adhesion molecule inhibitor. It binds to T cells and prevents them from migrating across the walls of blood vessels. Researchers believe that such migration causes inflammation and the resulting damage to nerve fibers that produces MS symptoms.3
Tysabri generally should be reserved for adults with relapsing-remitting MS who have not responded to or cannot tolerate other therapies. It should not be used in patients with compromised immune systems, and it should not be given concomitantly with medications that alter or weaken immune response. These cautions are necessary because Tysabri is itself an immunomodulator that increases patients' risk for PML and other opportunistic infections.
More frequently, patients receiving Tysabri experience headaches, fatigue, urinary tract infections, depression, joint pain, rash, and urinary urgency/frequency. Fewer than 1% of patients have had serious allergic reactions to Tysabri. Such reactions appear to be most common among patients who have developed antibodies to the medication, which is a recombinant version of the IgG molecule that is produced in mouse cells. When an allergic reaction occurs, Tysabri administration should be stopped immediately, symptoms should be treated, and the patient should not be restarted on the medication.
Tysabri is administered via intravenous infusion once every 4 weeks in a TOUCH-certified clinic. The product is supplied in single-use vials that contain 300 mg of natalizumab in 15 mL of clear solution. The concentrated drug must be mixed with 100 mL of 0.09% Sodium Chloride Injection, USP, before being infused over the course of an hour. Tysabri vials must be kept refrigerated at between 2?C and 8?C and should not be shaken.
In the AFFIRM trial, patients receiving Tysabri were 42% less likely than patients receiving placebo to experience sustained disability progression. The active-treatment patients also had significantly fewer new or enlarged lesions on brain tissues.4 Adding Tysabri to ongoing Avonex therapy produced significant positive results. Compared with patients receiving just Avonex, those receiving both Tysabri and Avonex had a 24% lower risk for disability progression.5
Tysabri has been found to improve cognitive function in MS patients and to reduce their need for steroids and hospital care.6,7 Although the medication is not indicated for Crohn's disease therapy, data presented at the American College of Gastroenterology show that Tysabri is effective for maintaining Crohn's remission for up to 2 years.8
Mr. Lamb is a freelance pharmacy writer living in Virginia Beach,Va, and president of Thorough Cursor Inc.
1. National Multiple Sclerosis Society. The Disease-Modifying Drugs. New York, NY: National Multiple Sclerosis Society; 2006.
2. Keely KA, Rivey MP, Allington DR. Natalizumab for the treatment of multiple sclerosis and Crohn's disease. Ann Pharmacother. 2005;39:1833-1843.
3. Tysabri (natalizumab) prescribing information. Cambridge, Mass, and San Diego, Calif: Biogen Idec Inc and Elan Pharmaceuticals Inc; 2006.
4. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354:899-910.
5. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354:911-923.
6. Fisher E, O'Connor PW, Havrdova E, et al. The effects of natalizumab on brain atrophy and cognitive function: results from the AFFIRM study. Paper presented at: Congress of the European Committee for Treatment and Research in Multiple Sclerosis; Madrid, Spain; September 28, 2006.
7. Lanker S. Natalizumab reduces corticosteroid use and hospitalizations and increases the proportion of disease-free multiple sclerosis patients. Poster presented at: Academy of Managed Care Pharmacy Educational Conference; Chicago, Ill; October 6, 2006.
8. Panaccione R, Colombel JF, Enns R, et al. Natalizumab maintains remission for 2 years in patients with moderately to severely active Crohn's disease and in those with prior infliximab exposure: results from an open-label extension study. Paper presented at: UnitedEuropean Gastroenterology Week; Berlin, Germany; October 24, 2006.