Tysabri

Multiple Sclerosis

Tysabri is approved to treat relapsing forms of multiple sclerosis (MS) in adults. This includes:

• Clinically isolated syndrome: A single episode of neurological symptoms that may be the first sign of MS.
• Relapsing-remitting disease: A form of MS where symptoms flare up and then mostly or completely disappear for a time.
• Active secondary progressive disease: A stage of MS that follows relapsing-remitting MS, where the disease continues to worsen with occasional relapses.

In patients with MS, this medication is used to decrease the number of flare-ups and help delay the worsening of physical disability.

Crohn's Disease

Tysabri is also used to treat adults with moderate to severe Crohn's disease who have evidence of inflammation. It is generally prescribed for individuals who have not responded well to, or cannot tolerate, conventional Crohn's disease therapies and medications known as tumor necrosis factor (TNF) inhibitors.

Because of the potential for serious side effects, healthcare providers often recommend Tysabri only when other treatments have not provided sufficient relief or are not appropriate for the patient.

Mechanism of Action

Tysabri (natalizumab) is a laboratory-made protein known as a monoclonal antibody. It is designed to recognize and attach to specific proteins on the surface of white blood cells, which are part of the body's immune system.

Blocking Immune Cell Movement

In conditions like multiple sclerosis (MS) and Crohn's disease, the immune system mistakenly attacks the body's own tissues. To do this, white blood cells must travel through the bloodstream and cross into the central nervous system or the gastrointestinal tract.

Tysabri works by:

• Binding to integrins: The medication attaches to a protein called alpha-4 integrin found on the surface of certain white blood cells.
• Preventing migration: By blocking these proteins, Tysabri prevents the immune cells from sticking to and passing through the lining of blood vessels.
• Reducing inflammation: Because the immune cells cannot reach the brain, spinal cord, or gut, they cannot cause the inflammation and damage associated with MS relapses or Crohn's disease flare-ups.

By limiting the number of inflammatory cells that reach these areas, the medication helps reduce the frequency of symptoms and may slow the progression of physical disability in patients with MS.

Common Side Effects

Many people using Tysabri experience mild to moderate side effects. These may include:

• Headache
• Fatigue
• Joint or muscle pain
• Urinary tract infections
• Lower respiratory infections, such as pneumonia
• Stomach pain, nausea, or diarrhea
• Vaginal yeast infections
• Depression
• Pain in the arms or legs

Infusion Reactions

Some side effects occur during or shortly after the intravenous infusion. These reactions are usually mild but can sometimes be severe. Symptoms may include:

• Dizziness
• Fever or chills
• Nausea
• Itching or rash
• Flushing
• Low blood pressure
• Chest pain

Serious Side Effects

While less common, Tysabri can cause serious health problems that require immediate medical attention:

• Liver Damage: Signs include yellowing of the skin or eyes (jaundice), dark urine, and unusual tiredness.
• Serious Infections: Tysabri increases the risk of a rare but serious brain infection called progressive multifocal leukoencephalopathy (PML). It also increases the risk of other infections, such as herpes meningitis or encephalitis.
• Allergic Reactions: Severe allergic reactions, including anaphylaxis, can occur. These typically happen within two hours of starting the infusion.
• Weakened Immune System: Because the medication affects the immune system, it may make it harder for the body to fight off various types of infections.

Progressive Multifocal Leukoencephalopathy (PML)

Tysabri is associated with an increased risk of PML, a rare brain infection caused by the JC virus. This condition typically results in death or severe disability. Risk factors for developing PML include:

• Presence of anti-JC virus antibodies.
• Longer duration of treatment, especially beyond 24 months.
• Prior use of immunosuppressant medications.

TOUCH Prescribing Program

Due to the risk of PML, Tysabri is only available through a restricted distribution program. Healthcare providers and patients must be enrolled in this program to ensure regular monitoring and awareness of the risks associated with the drug.

Serious Allergic Reactions

Hypersensitivity reactions, including anaphylaxis, have occurred in patients receiving Tysabri. These reactions usually happen during the infusion or within two hours after it is completed. Symptoms may include dizziness, fever, rash, itching, or difficulty breathing.

Liver Injury

Clinically significant liver injury has been reported. This can occur at any time during treatment, even after the first dose. Signs of liver damage include yellowing of the skin or eyes, dark urine, and elevated liver enzymes.

Infections

Tysabri increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella-zoster viruses. It may also increase the risk of other opportunistic infections. Patients with a weakened immune system due to other conditions or medications should be monitored closely.

Thrombocytopenia

A decrease in blood platelet counts (thrombocytopenia) has been observed, which can increase the risk of bleeding. Monitoring for symptoms such as easy bruising or prolonged bleeding from cuts is often recommended.

Pregnancy

There are no adequate and well-controlled studies of Tysabri in pregnant women. Animal studies have shown some potential for harm to the fetus, but animal studies do not always predict human response. If you are pregnant or planning to become pregnant, discuss the risks and benefits of continuing treatment with your healthcare provider.

If Tysabri is used during the third trimester of pregnancy, the newborn should be monitored for potential blood abnormalities. Some infants exposed to the medication late in pregnancy have experienced low levels of platelets (thrombocytopenia) or red blood cells (anemia).

Breastfeeding

Tysabri has been found in human breast milk. It is not yet known how the medication affects a nursing infant or the mother's milk production. Because of the potential for adverse reactions in the infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the medication to the mother's health.

Available Forms

Tysabri is supplied in the following form:

• Intravenous Injection: A sterile, preservative-free, concentrated solution that must be diluted before administration.

This medication is administered only as an infusion into a vein. It is not available as an oral medication, such as a tablet or capsule.

FDA Approval and Indications

Tysabri (natalizumab) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of:

• Relapsing forms of multiple sclerosis (MS): This includes clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults.
• Crohn's disease: It is used for adults with moderate-to-severe Crohn's disease who have not had an adequate response to, or are unable to tolerate, conventional therapies and certain other medications.

Boxed Warning and Safety Risks

The FDA requires a boxed warning for Tysabri because it increases the risk of progressive multifocal leukoencephalopathy (PML). PML is a rare but serious opportunistic viral infection of the brain that can lead to severe disability or death. Risk factors for developing PML include the presence of anti-JCV antibodies, longer duration of treatment, and prior use of immunosuppressant medications.

REMS Program

Because of the risk of PML, Tysabri is only available through a restricted distribution program called the TYSABRI REMS (Risk Evaluation and Mitigation Strategy). Under this program:

• Prescribers, pharmacies, and infusion centers must be specially certified.
• Patients must be enrolled in the program and meet specific requirements to receive the medication.
• Healthcare providers must monitor patients regularly for signs and symptoms of PML.

Regulatory History

Tysabri was originally approved in 2004 but was voluntarily withdrawn from the market in 2005 after reports of PML. Following a safety review, the FDA allowed the drug to return to the market in 2006 with the implementation of the mandatory REMS program to manage the associated risks.

The Infusion Process

Tysabri is given through a needle or catheter placed into a vein, usually in the arm. Each infusion session takes approximately one hour to complete. Because of the potential for serious side effects, the medication must be administered in a clinical setting or infusion center that is certified through a specific safety program called the TOUCH Prescribing Program.

Monitoring and Observation

After the infusion is finished, patients must remain at the facility for at least one hour of observation. This allows healthcare providers to monitor for signs of an allergic reaction or other infusion-related complications. If a reaction occurs, medical staff are available to provide immediate treatment.

Infusion Reactions

Some people may experience side effects during or shortly after the infusion. These can include:

• Dizziness or lightheadedness
• Nausea or vomiting
• Headache
• Fatigue
• Fever or chills
• Skin rash or hives
• Shortness of breath or chest pain

It is important to notify the healthcare provider immediately if any of these symptoms develop during or after the procedure. While most reactions occur during the infusion or within the first hour, some symptoms may appear later.