Can Aubagio cause PML as a side effect?

Key Points

• No, progressive multifocal leukoencephalopathy (PML) is not listed as a side effect for Aubagio (teriflunomide) in the manufacturer’s package insert. Aubagio is a treatment used for multiple sclerosis.
• Progressive multifocal leukoencephalopathy is a rare and often fatal infection of the brain that is caused by the John Cunningham (JC) virus.
• In addition to a weakened immune system from disease, medications that suppress the immune system can activate PML.

In 2012, the FDA approved Aubagio (teriflunomide), a once-daily, oral treatment used in patients with relapsing forms of multiple sclerosis (MS).

Aubagio is classified as a pyrimidine synthesis inhibitor and immunomodulator with anti-inflammatory properties. It works in MS by decreasing inflammation, lowering the number of white blood cells in the central nervous system, and protecting the nerves.

In studies, it has shown significant effect in reducing MS disease activity, including reducing relapses, slowing the progression of physical disability, and reducing the number of brain lesions.

The most common side effects with Aubagio include:

• elevated liver enzymes
• alopecia (hair loss)
• diarrhea
• influenza
• nausea
• paresthesia

What is PML?

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal infection of the brain that is caused by the John Cunningham (JC) virus.

In addition to a weakened immune system from disease, medications that suppress the immune system and treat autoimmune diseases can activate PML. These drugs include immunosuppressants to prevent rejection of organ transplants, multiple sclerosis (MS) agents, cancer treatments, and medicines for autoimmune diseases like lupus.

Many people acquire the JC virus in childhood with no symptoms, but a weakened immune system often activates the virus and allows it to multiply. Roughly half of the world's population are infected with the virus by the time they reach age 20, although most have no symptoms.

Some drugs used to treat MS or other autoimmune diseases can activate PML as a side effect.

What are the risk factors for PML?

• cancer (immune suppression such as in leukemia or lymphoma)
• HIV/AIDS
• organ transplant
• drugs that alter the immune system function (immune modulators)
• autoimmune disorders such as systemic lupus erythematosus (lupos)

What are the symptoms of PML?

There is a wide range of symptoms for PML, and they can progress over days to weeks, leading to disability and frequently death:

• loss of coordination or clumsiness loss of language ability, speaking or understanding speech (aphasia/dysphasia)
• memory loss (dementia)
• confusion
• vision problems, blurred vision
• weakness of the legs and arms that progresses
• personality changes

Which MS drugs can cause PML?

Patients with autoimmune conditions are at risk for PML. This includes diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus (lupus). Many of these patients are treated with biological therapies that can reactivate the JC virus.

MS drugs that warn about progressive multifocal leukoencephalopathy (PML) in their package insert include:

• alemtuzumab (Lemtrada)
• bafiertam (monomethyl fumarate)
• cladribine (Mavenclad)
• dimethyl fumarate (Tecfidera)
• diroximel fumarate (Vumerity)
• fingolimod (Gilenya)
• natalizumab (Tysabri)
• ocrelizumab (Ocrevus)
• ozanimod (Zeposia)
• rituximab (Rituxan)
• siponimod (Mayzent)

Other drugs associated with PML include immunosuppressants to prevent rejection of organ transplants, cancer treatments, and medicines for autoimmune diseases like lupus. Healthcare providers should monitor patients at risk for clinical symptoms or MRI findings that may suggest PML. MRI findings may be apparent before clinical signs or symptoms.

Bottom Line

• PML is a rare and often fatal infection of the brain and central nervous system that is caused by the John Cunningham (JC) virus.
• Progressive multifocal leukoencephalopathy (PML) is not listed as a side effect for Aubagio (teriflunomide) in the product label.
• Other multiple sclerosis drugs that have been linked with PML include: dimethyl fumarate (Tecfidera), fingolimod (Gilenya), natalizumab (Tysabri), ocrelizumab (Ocrevus), and rituximab (Rituxan), among others.

This is not all the information you need to know about Aubagio (teriflunomide) for safe and effective use. Review the full Aubagio information here, and discuss this information with your doctor or other health care provider.