INDICATION

TYSABRI® (natalizumab) is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See Important Safety Information regarding the risk of PML with TYSABRI. 

Click here to see additional Important Safety Information including Boxed Warning.

Browse video insights from healthcare professionals and actual TYSABRI patients on managing relapsing MS and treatment with TYSABRI.

Early treatment

Watch video of Simon Fishman, MD

"Early on...whether it’s a new diagnosis or somebody looking to make a change, I need to assess...is this person at high risk for progression.... The treatment really needs to match the risk for progression."

—Simon Fishman, MD

Watch video of Charles Smith, MD

“When people don’t follow the MRIs…oftentimes, the burden of disease has increased significantly and that limits the potential of any of our current medication.”

—Charles Smith, MD

Watch roundtable video of healthcare professionals

“If we are seeing clinical change, we need to offer…an aggressive option for patients.”

—Christopher LaGanke, MD

Watch video of Karen Blitz-Shabbir, DO

“If someone looks perfect, and they have one lesion on MRI…this is disease activity, and I think that we should have no tolerance."

—Karen Blitz-Shabbir, DO

Watch video of TYSABRI patient Keith

”I ended up going 2 years without any treatment…but it cost me a lot in that 2 years to not be on treatment. I’ll never get that back…. The one thing you do not do is nothing.”

—Keith, TYSABRI patient

Real-world experience

Watch video of Derrick Robertson, MD

"A patient that comes to mind is a younger guy, started off in his mid-20s…. He was having a pretty clear inadequate response based on MRI metrics…on having multiple relapses per year…. He needed a therapy that would hopefully impact his disease in a more positive way."

—Derrick Robertson, MD

Watch roundtable video of healthcare professionals

"It has an enduring effect, a benefit for our patients…. Now we know what we’re dealing with, so we can have that frank discussion of risk-benefit and feel really comfortable.”

—Christopher LaGanke, MD

Watch video of Christopher LaGanke, MD

“We fortunately have continuing evidence of risk…up to 6 years…for developing PML…. Risk changes…. Look at the benefit…. The risk of disease, I think, is also something that needs to be in that equation. All too often, that risk of under-treatment or no treatment is not discussed.”

—Christopher LaGanke, MD

Watch video of Christopher LaGanke, MD

“All along in our discussion with a patient who is on TYSABRI and [JCV]-positive, we update their risk of having PML and we also look at their benefit or efficacy on this treatment…. It’s a continual reassessment of risk/benefit.”

—Christopher LaGanke, MD

Watch video of Karen Blitz-Shabbir, DO

“For people who are [JCV]-positive, there’s ways to make sure that people feel that they’re being observed and monitored closely enough.”

—Karen Blitz-Shabbir, DO

Watch roundtable video of healthcare professionals

"If we have a patient who is [JCV]-negative, I feel that the risk remains low and effective therapies’ benefits overweigh the potential risk.”

—Regina Berkovich, MD, PhD

Watch video of Stephen Newman. MD and TYSABRI patient Jennifer

“What they said was happening in the clinical trials [is] actually happening in the real world. It was as effective for me as it was in the clinical trials.”

—Jennifer, TYSABRI patient

Watch video of TYSABRI patient Bryan

“For me, the benefits of TYSABRI outweighed the risks. My experience with TYSABRI has been great.”

—Bryan, TYSABRI patient

Watch roundtable video of TYSABRI patients

“I am JCV antibody–positive, and so…I face a greater risk. But it is certain that I have relapsing MS…. So for me, it’s a greater risk not to be on it.”

—Amy, TYSABRI patient

Watch video of Regina Berkovich, MD, PhD

"When I am talking to the patient about risks and benefits of TYSABRI…it’s not about numbers really, because patients would like to hear about your professional experience with it…. It’s important to explain to the patient how the medication works. And I think it’s important for the patient to understand."

—Regina Berkovich, MD, PhD

Team monitoring

Watch video of Charles Smith, MD

"The nurse tells me about patient compliance…are they following through with recommendations…and talks about patient symptoms…. Our nurses are really on top of this. They really go through a check-list…. This is really a vital element of my ongoing assessment of patients who are on TYSABRI therapy.”

—Charles Smith, MD

Watch video of Stephen Newman, MD and TYSABRI patient Jennifer

“The infusion [center] nurses…are knowledgeable in the sense where they know how…and they know when to react.”

—Jennifer, TYSABRI patient

Watch video of healthcare professionals

“As a physician, I consider myself to really be part of [the] clinical care team.... The infusion nurses help monitor...on a monthly basis or more. The nurse practitioners can intervene if there's a problem in the infusion clinic.... This cohesiveness helps to optimize [patient] care.”

—John Foley, MD

Watch video of healthcare professionals

“TOUCH-certified infusion centers have met with the safety standards that are necessary for TYSABRI infusion.... Because your patients come in every 28 days for their TYSABRI infusions, you and your staff have the opportunity to develop a relationship with these patients.”

—Carter Davis, Account Manager

Watch video of TYSABRI patients

“The team of nurses are there and they’re in contact with my doctor and the TOUCH Program… That makes me feel...good that they’re watching me and they know how I’m doing.”

—Vern, TYSABRI patient

Patient support

Watch video of TYSABRI patients

“It’s very important for people to seek out a neurologist and other physicians that they…can work closely with…. When you have a doctor who supports you…it’s very helpful.”

—Courtney, TYSABRI patient

Watch video of healthcare professionals and TYSABRI patient Heidi

“This is a team effort. We have multiple people on [their] clinical care team that are there to help... as their support that they can lean on in times that are challenging."

—John Foley, MD

Watch video of healthcare professionals

“Services that are provided by Above MS range from financial assistance programs for patients to support coordinators that are available to talk to the patient on the phone. We also provide access to a peer community where patients with MS can connect with other patients with MS…. Above MS will perform a benefits investigation on behalf of the office.... In addition, they'll help them to navigate the prior authorization process.”

—Carter Davis, Account Manager

Watch roundtable video of TYSABRI patients

“My infusion nurse along with my neurologist…and Biogen was able to assist me with getting...my infusions every month…. So I am a big advocate for having the right type of support in your corner.”

—Erica, TYSABRI patient

Watch roundtable video of TYSABRI patients

"When you learn how to advocate for yourself, you have a great relationship with your doctor, with your neurologist. You have a great support system.”

—Erica, TYSABRI patient

Indication

TYSABRI® (natalizumab) is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See Important Safety Information regarding the risk of PML with TYSABRI.

IMPORTANT SAFETY INFORMATION

WARNING: Progressive Multifocal Leukoencephalopathy (PML)

TYSABRI® (natalizumab) increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI.

Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended.

Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH Prescribing Program.

  • Infection by the JC Virus (JCV) is required for the development of PML.
  • There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs.
  • Postmarketing data suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value).
  • MRI findings may be apparent before clinical signs or symptoms suggestive of PML. Monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following TYSABRI discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis.
  • PML has been reported after discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for approximately 6 months after discontinuation of TYSABRI.
  • Adverse events that may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI-treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation.
  • JCV infection of granule cell neurons in the cerebellum, i.e., JCV granule cell neuronopathy (GCN), with symptoms similar to PML, has been reported in patients treated with TYSABRI. JCV GCN can occur with or without concomitant PML and can cause cerebellar dysfunction. Diagnosis and management of JCV GCN should follow guidance provided for PML.
  • Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI-treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It presents as a clinical decline in the patient’s condition after TYSABRI removal (and, in some cases, after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In TYSABRI-treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.

Contraindications

  • TYSABRI is contraindicated in patients who have or have had PML.
  • TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI.

TYSABRI TOUCH Prescribing Program

  • Because of the risk of PML, TYSABRI is available only through a restricted distribution program under a REMS called the TOUCH® Prescribing Program.
  • Patients must be enrolled in the TOUCH Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI and complete and sign the Patient-Prescriber Enrollment Form.

Herpes Infections – Encephalitis, Meningitis and Acute Retinal Necrosis

  • TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses.
  • Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI.
  • The duration of treatment with TYSABRI prior to onset ranged from a few months to several years.
  • Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered.
  • Patients being administered TYSABRI are at a higher risk of acute retinal necrosis (ARN), a fulminant viral infection of the retina caused by the family of herpes viruses. Patients with eye symptoms such as decreased visual acuity, redness or eye pain should be referred for retinal screening as serious cases of ARN can lead to blindness of one or both eyes.
  • Following clinical diagnosis of ARN consider discontinuation of TYSABRI.

Hepatotoxicity

  • Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting.
  • Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses.
  • TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence).

Hypersensitivity/Antibody Formation

  • Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%.
  • Reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain.
  • If a hypersensitivity reaction occurs, discontinue administration of TYSABRI and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI.
  • Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared with patients who did not develop antibodies to TYSABRI in both MS and CD studies.
  • Patients who receive TYSABRI for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment.

Immunosuppression/Infections

  • The immune system effects of TYSABRI may increase the risk for infections.
  • In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in TYSABRI-treated patients than in placebo-treated patients. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1.
  • In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids.
  • In a long-term safety study of patients, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of TYSABRI-treated patients.
  • Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections over the risk observed with use of TYSABRI alone.
  • In Studies MS1 and MS2, the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebo-treated patients.
  • In Study MS1, the incidence of serious infections was approximately 3% in TYSABRI-treated patients and in placebo-treated patients. Most patients did not interrupt treatment with TYSABRI during infections.

Laboratory Test Abnormalities

  • In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient.

Adverse Reactions

  • The most common adverse reactions reported at an incidence of ≥10% with TYSABRI and ≥2% difference with placebo were headache (38% vs 33%), fatigue (27% vs 21%), infusion reactions (24% vs 18%), urinary tract infections (21% vs 17%), arthralgia (19% vs 14%), depression (19% vs 16%), pain in extremity (16% vs 14%), rash (12% vs 9%), gastroenteritis (11% vs 9%), and vaginitis (10% vs 6%).
  • The most frequently reported serious adverse reactions in Study MS1 were infections (3.2% vs 2.6% placebo), including urinary tract infection (0.8% vs 0.3%) and pneumonia (0.6% vs 0%), acute hypersensitivity reactions (1.1% vs 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% vs 0%]), depression (1.0% vs 1.0%, including suicidal ideation or attempt [0.6% vs 0.3%]), and cholelithiasis (1.0% vs 0.3%).
  • Based on animal data, TYSABRI may cause fetal harm. TYSABRI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Please see full Prescribing Information, including Boxed Warning.

ARR = annualized relapse rate.

References: 1. TYSABRI Prescribing Information, Cambridge, MA: Biogen. 2. Polman CH, O'Connor PW, Havrdova E, et al; the AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899-910.