PML Risk Calculator
JC Virus Antibody Index Risk Calculator
Based on data from Tysabri clinical studies, enter your JC virus antibody index to see your PML risk over 4 years.
Imagine taking a medication that controls your MS or Crohn’s disease - but could also silently trigger a rare brain infection you’ve never heard of. That’s the reality for some people on powerful immunosuppressants. Progressive Multifocal Leukoencephalopathy, or PML, isn’t something you catch from a sneeze. It’s a hidden threat that wakes up inside you when your immune system is turned down too low.
What Is PML, Really?
PML is not a new disease. It was first described in 1958, but it’s only in the last 20 years that we’ve connected it directly to modern immunosuppressant drugs. At its core, PML is caused by the John Cunningham (JC) virus - a common virus that lives quietly in about 60% of adults without causing harm. But when your immune system is weakened - especially by drugs that block key immune cells - that virus wakes up, attacks the white matter of your brain, and destroys the fatty coating (myelin) that lets nerve signals travel fast.
Unlike a stroke or a tumor, PML doesn’t show up on a regular scan right away. It creeps in slowly: a stumble you can’t explain, blurred vision that comes and goes, trouble finding the right words. By the time symptoms are obvious, the damage is often advanced. About 30% to 50% of people with PML die. Those who survive often live with permanent weakness, speech loss, or cognitive decline.
Which Drugs Carry the Highest Risk?
Not all immunosuppressants are equal when it comes to PML risk. Some are far more dangerous than others.
Natalizumab (Tysabri) is the biggest concern. Used for multiple sclerosis and Crohn’s, it blocks immune cells from entering the brain - which helps reduce inflammation, but also gives the JC virus a free pass to multiply. Through 2011, 102 cases of PML were confirmed in over 82,000 people treated with Tysabri. That’s about 0.12% overall. But risk skyrockets if you have three things: you’re JC virus antibody positive, you’ve taken another immunosuppressant before (like azathioprine or methotrexate), and you’ve been on Tysabri for more than two years. In that group, the risk jumps to 4.1 cases per 1,000 patients.
Other drugs carry lower - but still real - risks:
- Fingolimod (Gilenya): 0.4 cases per 1,000 patient-years
- Dimethyl fumarate (Tecfidera): 0.2 cases per 1,000 patient-years
- Rituximab (Rituxan): 0.8 cases per 1,000 patient-years
- Ibrutinib (Imbruvica): 0.3% in blood cancer patients
Drugs like interferon beta and glatiramer acetate? No confirmed PML cases. That’s why many neurologists now start with these safer options before moving to higher-risk drugs.
How Do Doctors Measure Your Risk?
Before starting natalizumab, your doctor must test you for JC virus antibodies. It’s not just a yes-or-no answer. The test gives you an index number - a number that tells how much virus exposure you’ve had.
Here’s what that number means:
- Index below 0.9: 0.09% risk of PML after 4 years
- Index between 0.9 and 1.5: 0.9% risk after 4 years
- Index above 1.5: 10.9% risk after 4 years
That’s a huge difference. A person with an index over 1.5 has more than a 1 in 10 chance of getting PML if they stay on Tysabri long-term. That’s why many doctors stop treatment after 2 years for people with high index values - even if their MS is under control.
But here’s the catch: 2 to 3% of people test negative for JC virus antibodies - even though they actually carry the virus. That’s called a false negative. One Reddit user described how his PML was found on an MRI after 18 months on Tysabri, despite a negative antibody test. That’s why doctors now combine antibody tests with regular brain scans.
What Does Monitoring Look Like?
If you’re on a high-risk drug, you’re not just getting a prescription. You’re entering a monitoring program.
The FDA requires all doctors prescribing natalizumab to complete special training. They must check your JC virus status before you start. They must ask: Have you ever taken another immunosuppressant? And they must schedule regular MRIs - every 3 to 6 months.
Why MRIs? Because early PML lesions look different from regular MS plaques. They’re small, bright spots on diffusion-weighted imaging. But reading them takes skill. Neurologists need 15 to 20 hours of training to spot them reliably. That’s why many community clinics miss early signs - and why academic hospitals have better outcomes.
Some patients also get blood tests to check their lymphocyte count. If your absolute lymphocyte count drops below 0.8 x 10⁹/L, your PML risk jumps 4.3 times. That’s not always tracked - but it should be.
What Happens If PML Is Found?
There’s no cure for PML. But stopping the drug that caused it is step one. For many, that’s enough to slow or even stop the virus.
But here’s the twist: 50% to 60% of people develop something called IRIS - immune reconstitution inflammatory syndrome. That’s when your immune system wakes up, sees the virus in your brain, and goes into overdrive. It attacks the infected tissue - and sometimes causes more damage than the virus itself.
IRIS can be deadly. But it’s treatable. High-dose steroids like methylprednisolone are often used to calm the inflammation. One patient on Reddit shared that after stopping Tysabri and starting steroids, he regained 90% of his motor function within six months. That’s rare - but it happens.
What Are People Really Feeling?
Behind the statistics are real people living with constant fear.
A survey on the National Multiple Sclerosis Society’s forum found that 78% of people on natalizumab felt extreme anxiety about PML. More than half said they’d quit the drug after two years - even if it was working perfectly. One woman wrote: "I don’t care if my legs feel better. I’d rather walk slowly than die from a brain infection."
On the flip side, some patients feel relieved when they switch to safer drugs. Since 2015, prescriptions for natalizumab have dropped 22% in people with prior immunosuppressant use. Ocrelizumab, a newer drug with lower PML risk, has seen a 35% rise in use in this group.
That anxiety isn’t irrational. It’s based on real data. And it’s why doctors now spend more time talking about risk than ever before.
What’s Changing in 2025?
Hope is on the horizon.
A new experimental therapy called DIAVIS T-cell therapy showed a 68% reduction in death and 45% better recovery in a small 2024 trial. Immune checkpoint inhibitors like pembrolizumab are being tested in PML cases - with some success. And the Cleveland Clinic just started a Phase II trial in early 2025 testing maraviroc, an HIV drug, to prevent PML in high-risk natalizumab patients.
By 2030, experts predict PML risk from natalizumab could fall to 0.5 cases per 1,000 patient-years - thanks to better testing, smarter monitoring, and new treatments. That might bring it back as a first-line option for select patients.
For now, the message is clear: don’t ignore the risk. Don’t assume you’re safe because you feel fine. Get tested. Get scanned. Ask questions. Your brain is worth it.
Can you get PML from over-the-counter supplements?
No. PML is only linked to prescription immunosuppressants that significantly weaken cell-mediated immunity - like natalizumab, fingolimod, or rituximab. Over-the-counter supplements, even those that claim to "boost" or "modulate" immunity, don’t suppress the immune system enough to trigger JC virus reactivation. There are no documented cases of PML from vitamins, herbs, or probiotics.
Is PML contagious?
No. You cannot catch PML from someone else. The JC virus spreads through saliva or respiratory secretions - but almost everyone gets it in childhood without symptoms. PML only happens when your own immune system is damaged by medication, not from exposure to another person with PML.
How often should I get an MRI if I’m on natalizumab?
Every 3 to 6 months, starting after 12 months of treatment. If your JC virus antibody index is above 1.5, your doctor may recommend scans every 3 months. If your index is low and you’ve never taken other immunosuppressants, scans every 6 months may be enough. Never skip a scan - early detection saves function.
What if my JC virus test is negative but I still get PML?
It happens. About 2 to 3% of people have false-negative JC virus tests. That’s why doctors don’t rely on the test alone. If you develop new neurological symptoms - even with a negative test - an MRI is required immediately. Don’t wait. Early MRI findings can confirm PML before symptoms worsen.
Can I switch from natalizumab to another drug safely?
Yes - and many people do. Switching to lower-risk drugs like ocrelizumab, dimethyl fumarate, or teriflunomide is common, especially after 2 years on natalizumab or if your JC virus index is high. Your neurologist will plan a transition to avoid MS flare-ups. Most patients transition without major issues, and the drop in PML risk is worth it.
