Class: Monoclonal antibodies, anti-integrin
Name: Natalizumab (Tysabri®)
General Dosage: Given intravenously once per month at infusion center.
Mechanism of Action: Blocks ability of B cells to migrate into the brain.
Effectiveness: Highly effective: decreases relapses by 67%; decreases MRI activity by 80%; decreases brain volume loss by 45%.
Possible Side Effects: Boxed warning for PML***. Heightened risk for herpes encephalitis and meningitis, liver toxicity, hypersensitivity (including anaphylaxis) reaction, heightened risk of infection. Only available through REMS**. Note: repeated negative testing for the JC virus that causes PML*** can dramatically minimize the risk of PML***.
NOTE: Natalizumab is considered by Rocky Mountain MS Center neurologists as a “First Line” treatment for patients who test and remain negative for the JC virus, and “Fourth Line” (not recommended) for patients who have been exposed to the JC virus. This difference is related to the possible risk of PML.
Natalizumab, commonly known as the brand name Tysabri, works by blocking the passage of inflammatory immune cells through the blood brain barrier, thus slowing the progression of MS. After first receiving FDA approval in 2004, Tysabri was pulled from the U.S. market when it was linked to three cases of PML. In 2006 it was returned to the market after the safety profile was further explored.
The risk of PML is related to the fact that Tysabri may, in fact, work too well. For most people, the immune system would fight off PML without any difficulty, but because Tysabri is designed to fully block the MS immune attack on the brain, it also blocks the immune system’s ability to fight infections in the brain, such as PML. It appears, however, to have little if any problematic effect on other types of infections.
PML infection has been found to be directly related to the presence of the John Cunningham virus (JCV), a type of human polyomavirus. Therefore, patients must be tested for the presence of JCV before being prescribed Tysabri, and monitored while taking the drug. For JCV-negative patients, Tysabri is considered a first-line, highly-efficacious MS treatment.
Dr. Timothy Vollmer retired as Medical Director of the Rocky Mountain MS Center in 2021. The above video was recorded in 2015.
** REMS (Risk Evaluation and Mitigation Strategy): REMS is a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.
*** PML (Progressive Multifocal Leukoencephalopathy): PML is a rare but serious brain infection that is caused by the JC Virus (JCV). PML is seen in MS patients who are JC virus (JCV) positive and on disease modifying therapies known to increase the risk of PML. At least 50% of the general population has been exposed to JCV, but the infection is generally asymptomatic. But, in immunocompromised patients, including those taking certain MS DMTs, the JC Virus can infect the brain and result in PML. PML The first case of PML in MS was discovered in 2005 with the use of Tysabri.