Study Shows That People with MS Taking Natalizumab Develop Antibodies to the JC Virus at Higher Than Normal Rates, Emphasizing Need for Regular Monitoring January 27, 2016 A study by researchers in Germany and France observed changes in JC virus antibody status in two large groups of people with MS followed for 15 and 24 months. Having a positive antibody test to the virus means that a person has been exposed to the virus and has a higher risk of PML (a rare brain disease) than a person who has a negative antibody test, but a positive antibody test does not mean that a person has or will get PML.

The investigators found that a higher percentage of individuals’ blood tests changed from negative to positive in people treated with natalizumab than in people with MS who were not treated with natalizumab. They also found that levels (called the index) of antibodies in those who were already positive increased overall over time.

The results emphasize the need for vigilant monitoring of people with MS taking natalizumab, including regular antibody testing, MRI monitoring to improve detection of PML, and clinical monitoring for early signs suggesting the possibility of PML.

Decisions to initiate, continue or discontinue natalizumab need to include a conversation about the risk of PML, the risk of worsening MS and the potential adverse effects and the efficacy of alternative therapies.

The study, led by Heinz Wiendl, MD (University of Münster, Germany), was published January 27, 2016 in the online issue of Neurology Neuroimmunology and Neuroinflammation.

Background: ® Biogen) is given by infusion into the vein every four weeks. Although it can be very effective in reducing disease activity in people with relapsing MS, a small proportion of people taking Tysabri develop a rare brain disease called PML (progressive multifocal leukoencephalopathy). PML is caused by the activation of a virus called the JC (John Cunningham) virus. PML has also occurred in people taking other powerful immune-modifying therapies for MS, including fingolimod (® Biogen).



A blood test is available to test for the presence of antibodies (immune proteins), directed against the JC virus. Most people get this test before starting therapy with natalizumab, and every six months while they are taking it. Having a positive antibody test to the virus means that a person has been exposed to the virus and has a higher risk of developing PML than a person who has a negative antibody test. However, testing positive to JC antibodies does not mean a person has or will definitely get PML. Since the JC virus is common, generally about half of adults have antibodies to the JC virus. Research suggests that the expected rate of people in the general population changing (“seroconversion”) from antibody negative to antibody positive is about 1 percent per year.



Recent evidence also suggests that having higher levels (called the index) of JC virus antibodies is an indicator of re-exposure to the virus or that the immune system is not fighting the virus adequately, which can further define risks of developing PML.



The Study: This study observed changes in JC virus antibody status in two groups of people with MS: a group from Germany followed for about 15 months and a group from France followed for about 24 months. The investigators found that seroconversion rates in people treated with natalizumab were higher (from 8.5 to 10.3% per year) than those found in people with MS who were not treated with natalizumab. They also found that levels of antibodies in those who were already positive increased over time. This overall increase was largely the result of changes seen in about 20 percent of the people observed; levels for the other 80% remained stable over the observation period.



The study, led by Heinz Wiendl, MD (University of Münster, Germany), was published



Comment: Although this study found seroconversion rates that were higher than expected among those taking natalizumab, and found an overall increase of antibody levels among those who were already antibody positive, the majority who were negative at the start of the study were still negative after the observation period;

the majority of those who were JC virus antibody positive at the beginning of the study had stable levels of antibodies over the course of the study; and

the majority of individuals taking natalizumab who are JC virus antibody positive do not develop PML.

“This study emphasizes the need for vigilant monitoring of people with MS taking natalizumab, including regular antibody testing, MRI monitoring to improve detection of PML, and clinical monitoring for early signs suggesting the possibility of PML,” noted Bruce A. Cohen, MD, Professor, Davee Department of Neurology and Clinical Neurosciences at Northwestern University’s Feinberg School of Medicine, and Chair of the National MS Society’s National Medical Advisory Committee. “Natalizumab is a very effective disease-modifying therapy for relapsing MS, and any decision to discontinue this therapy in a person who is doing well on it needs to balance the risk of PML against their risk of worsening MS, and the potential adverse effects and efficacy of alternate therapies.”



Read the





NOTE: Prescribing information for natalizumab recommends that individuals taking this therapy call their healthcare provider right away if they experience any new or worsening medical problems that have lasted several days. These may be new or sudden and include problems with: thinking; eyesight; strength; balance; weakness on one side of the body; using the arms and legs.



Gilenya is a registered trademark of Novartis AG.

Tysabri is a registered trademark of Biogen.

Tecfidera is a registered trademark of Biogen.



Frequently Asked Questions



Q: Based on this study’s results, should I stop taking Tysabri?

A: This question should be discussed with an individual’s healthcare provider. Tysabri is a very effective disease-modifying therapy for relapsing MS. Decisions to initiate, continue or discontinue natalizumab need to include a conversation about the risk of PML, the risk of worsening MS and the potential adverse effects and the efficacy of alternative therapies.



Q: Should I stop taking Tysabri as soon as the JCV antibody levels increase?

A: The answer to this question depends on a variety of factors. A rise in antibody levels should trigger a discussion about balancing potential benefits and risks.



Q: How often am I supposed to get my blood checked for JC antibodies?

A: The standard recommendation is that testing for JC virus antibodies be done every six months in people taking natalizumab who are antibody negative in order to detect potential conversion to a positive status, but many prescribers recommend antibody testing at more frequent intervals in both those who are antibody negative and those who are antibody positive.



Q: What are symptoms of PML?

A: The symptoms of PML are diverse and can be similar to MS symptoms. For this reason individuals should be alert to any new or worsening symptoms and report them promptly to their MS healthcare provider. Symptoms may be new and include problems with: thinking; eyesight; strength; balance; weakness on one side of the body; using the arms and legs. Natalizumab (Tysabri,Biogen) is given by infusion into the vein every four weeks. Although it can be very effective in reducing disease activity in people with relapsing MS, a small proportion of people taking Tysabri develop a rare brain disease called PML (progressive multifocal leukoencephalopathy). PML is caused by the activation of a virus called the JC (John Cunningham) virus. PML has also occurred in people taking other powerful immune-modifying therapies for MS, including fingolimod ( Gilenya,® Novartis AG) and dimethyl fumarate ( Tecfidera Biogen).A blood test is available to test for the presence of antibodies (immune proteins), directed against the JC virus. Most people get this test before starting therapy with natalizumab, and every six months while they are taking it. Having a positive antibody test to the virus means that a person has been exposed to the virus and has a higher risk of developing PML than a person who has a negative antibody test. However, testing positive to JC antibodies does not mean a person has or will definitely get PML. Since the JC virus is common, generally about half of adults have antibodies to the JC virus. Research suggests that the expected rate of people in the general population changing (“seroconversion”) from antibody negative to antibody positive is about 1 percent per year.Recent evidence also suggests that having higher levels (called the index) of JC virus antibodies is an indicator of re-exposure to the virus or that the immune system is not fighting the virus adequately, which can further define risks of developing PML.This study observed changes in JC virus antibody status in two groups of people with MS: a group from Germany followed for about 15 months and a group from France followed for about 24 months. The investigators found that seroconversion rates in people treated with natalizumab were higher (from 8.5 to 10.3% per year) than those found in people with MS who were not treated with natalizumab. They also found that levels of antibodies in those who were already positive increased over time. This overall increase was largely the result of changes seen in about 20 percent of the people observed; levels for the other 80% remained stable over the observation period.The study, led by Heinz Wiendl, MD (University of Münster, Germany), was published January 27, 2016 in the online issue of Neurology Neuroimmunology and Neuroinflammation.Although this study found seroconversion rates that were higher than expected among those taking natalizumab, and found an overall increase of antibody levels among those who were already antibody positive,“This study emphasizes the need for vigilant monitoring of people with MS taking natalizumab, including regular antibody testing, MRI monitoring to improve detection of PML, and clinical monitoring for early signs suggesting the possibility of PML,” noted Bruce A. Cohen, MD, Professor, Davee Department of Neurology and Clinical Neurosciences at Northwestern University’s Feinberg School of Medicine, and Chair of the National MS Society’s National Medical Advisory Committee. “Natalizumab is a very effective disease-modifying therapy for relapsing MS, and any decision to discontinue this therapy in a person who is doing well on it needs to balance the risk of PML against their risk of worsening MS, and the potential adverse effects and efficacy of alternate therapies.”Read the study and an editorial commenting on the study Read prescribing information for natalizumabNOTE: Prescribing information for natalizumab recommends that individuals taking this therapy call their healthcare provider right away if they experience any new or worsening medical problems that have lasted several days. These may be new or sudden and include problems with: thinking; eyesight; strength; balance; weakness on one side of the body; using the arms and legs.Gilenya is a registered trademark of Novartis AG.Tysabri is a registered trademark of Biogen.Tecfidera is a registered trademark of Biogen.This question should be discussed with an individual’s healthcare provider. Tysabri is a very effective disease-modifying therapy for relapsing MS. Decisions to initiate, continue or discontinue natalizumab need to include a conversation about the risk of PML, the risk of worsening MS and the potential adverse effects and the efficacy of alternative therapies.The answer to this question depends on a variety of factors. A rise in antibody levels should trigger a discussion about balancing potential benefits and risks.The standard recommendation is that testing for JC virus antibodies be done every six months in people taking natalizumab who are antibody negative in order to detect potential conversion to a positive status, but many prescribers recommend antibody testing at more frequent intervals in both those who are antibody negative and those who are antibody positive.The symptoms of PML are diverse and can be similar to MS symptoms. For this reason individuals should be alert to any new or worsening symptoms and report them promptly to their MS healthcare provider. Symptoms may be new and include problems with: thinking; eyesight; strength; balance; weakness on one side of the body; using the arms and legs. Learn more about the risk factors and symptoms of PML from the web site of The PML Consortium.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.