Natalizumab is an FDA-approved, monoclonal antibody approved for the treatment of multiple sclerosis and Crohn's disease. The drug was originally approved to treat multiple sclerosis in 2004, but after reported cases of death due to progressive multifocal leukoencephalopathy during treatment with natalizumab, the FDA removed the drug from the market. In 2006, the FDA reintroduced the drug when multiple protests by those with multiple sclerosis advocated for the use of natalizumab in conjunction with the establishment of an advisory committee that would monitor those on natalizumab. All patients receiving treatment with natalizumab are part of a database called the TOUCH Prescribing Program in which a facility is granted permission by the United States Federal Drug Administration to administer natalizumab and ensure the extensive monitoring data and follow up regarding the patient's experience with natalizumab is collected. 
Natalizumab has shown to slow down the progression of symptoms during a flare-up in individuals with multiple sclerosis and decrease the rate of relapse in those with relapsing-remitting multiple sclerosis. In a randomized, placebo-controlled study, 77% of patients were relapse-free at the end of 1 year compared to 56% of those on placebo. The 2-year relapse-free rate was 67% with natalizumab versus 41% with placebo. When the MRI images of its participants receiving natalizumab versus placebo were compared, the results showed 83% reduction in the number of lesions detected by T2 weighted MRI and 83% fewer lesions on the gadolinium-enhanced MRI images of patients who received natalizumab over those who received placebo. A controlled trial of natalizumab compared the average number of new lesions in a 6-month period between 3 groups: a placebo group, those on 3 mg/kg of natalizumab, and those on 6 mg/kg of natalizumab. The average number of new lesions per patient in the placebo group was 9.6 compared to 0.7 and 1.1 for those on natalizumab 3-mg and 6-mg therapy, respectively.
Natalizumab is a monoclonal antibody that binds to alpha-4 integrin receptors on endothelial cells lining blood vessels. Integrins are a class of selective adhesion molecules composited of multiple subunits and as a class aid in the chemotaxis of leukocytes to sites of inflammation throughout the body. Natalizumab decreases inflammation by adhering to the receptors that would bind these integrins during an inflammatory flare, and thereby directly blocks leukocytes from crossing the blood vessel and exerting pro-inflammatory responses. In patients with multiple sclerosis, natalizumab blocks alpha4-beta1 integrin receptor that lines the blood-brain barrier, blocking leukocytes from entering the central nervous system (CNS) of the patient. Several studies have shown a significant reduction in the number of lesions in multiple sclerosis patients taking natalizumab.
Natalizumab is administered via intravenous infusions every 28 days at a TOUCH Prescribing Program approved site. The recommended dose is 300 mg/15 mL (20 mg/mL); however, this dose can be modified at the discretion of the treating physician. The infusion itself takes 1 hour, and the patient is then monitored closely by staff an hour after for any significant side effects. Natalizumab should not be given as an intravenous bolus or push. The drug should be administered within 8 hours of preparation.
While the risk of acquiring progressive multi leukoencephalopathy with treatment can be daunting, given the current evidence at hand, one can take measures to best decrease the probability. As mentioned before:
Three risk factors have been associated with a decreased incidence of PML which include (1) that the patient was on Natalizumab for the shortest period, (2) the patient did not have a large list of immunosuppressant drug use in his or her history, and (3) those patients who were negative for virus antibodies. The incidence of PML in a low-risk group (as defined by those mentioned above) was 0.09 cases per 1000 patients, compared to the high-risk group’s 11.1 cases per 1000 patients. 
Checking for anti-JC antibodies can helpful but not definitive for the risk stratification of acquiring PML. Those who are negative for the antibody have a decreased risk, but it does not provide 100% immunity against acquiring PML. Therefore, periodic testing should be done for anti-JC antibodies while a patient is on natalizumab.
The long-term effects of natalizumab have yet to be determined. It is the responsibility of the physician to have a thorough discussion regarding the risks and benefits of treatment with their patient.
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