Tysabri - Frequently Asked Questions
Updated April 13, 2007
Introduction: Following the September 2006 Health Canada
approval of Tysabri® (natalizumab) for relapsing multiple
sclerosis, Biogen Idec and Elan Pharmaceuticals commercially
launched
the drug in Canada. The drug is given by monthly intravenous
infusion.
About Tysabri and Its Availability
Q. What is Tysabri (pronounced Tie-SAB-bree) and how does
it work?
A. Tysabri (whose scientific name is natalizumab, pronounced:
nat-tal-IZ-zue-mab) is a laboratory-produced monoclonal antibody.
It was formerly called Antegren. It had been approved for marketing
by Health Canada for relapsing forms of MS, based on data from
the first year of two, two-year clinical trials.
Tysabri is designed to hamper the movement of potentially damaging
immune cells from the bloodstream, across the "blood-brain
barrier," and into the brain and spinal cord. The drug
inhibits this movement by attaching to alpha 4-integrin, a
protein on the surface of immune T-cells that normally enables
them to adhere to and pass through the blood-brain barrier.
Because of this mode of action, Tysabri is called a selective
adhesion molecule inhibitor (or "SAM").
This approach was initially studied in animal models, which
showed that monoclonal antibodies could block such immune cell
movement and ameliorate disease. These animal studies led to
the successful human studies.
Q. Who should take Tysabri?
A. Tysabri has been approved for persons
with relapsing remitting multiple sclerosis.
Relapsing MS means that individuals experience flare-ups
of symptoms in the form of periodic attacks, which then subside
with total or partial recovery.
According to the Health Canada approval, Tysabri is generally
recommended for people who have had inadequate response to,
or are unable to tolerate, other approved MS therapies. The
question of who should take Tysabri is something that can only
be answered through discussions between an individual and his
or her neurologist.
Q. Who should not take Tysabri?
A. People should NOT take Tysabri if they have:
- An allergy or sensitivity to natalizumab or anything
else that is in this medication.
- A serious problem with their immune system (for example, due
to a disease such as leukemia or human immunodeficiency
virus[HIV], or from using some other mediations that weaken the immune
system)
- A type of rare infection of the brain called progressive multifocal
leukoencephalopathy[PML] or have had it in the past.
Q. In terms of who can be prescribed Tysabri, who determines
what constitutes an "inadequate response" to currently
approved MS therapies?
A. Canada’s approval of Tysabri does not specifically
define "inadequate response," nor does it define
what constitutes an inability to tolerate alternate MS therapies.
Therefore, the decision about whether to take or switch to
Tysabri must be made after careful consideration by a person
with MS together with his or her personal physician.
Q. How much will Tysabri cost?
A. The wholesale price of Tysabri which is administered 13
times per year, is $39,640 annually as stated in Biogen Idec’s
submission to the Common Drug Review (CDR)-(see next question.)
Q. Will Tysabri be reimbursed by my provincial drug plan?
A. None of the provincial governments are as yet reimbursing
the cost of Tysabri. Biogen has submitted to the Common Drug
Review (CDR) process. This is the first step in applying to
most provincial drug formularies for listing. CDR is the government
agency that determines whether a drug is cost-effective and
should be covered by public drug programs. Provincial drug
programs use this information in making their decisions. According
to Biogen Idec, CDR should make a preliminary decision by late
February with a public decision in March.
The Society will work closely with the companies to ensure
that they pursue their commitment of providing access for those
people with MS for whom this treatment may be appropriate.
Q. Will my insurance cover the cost of Tysabri?
A. According to Biogen Idec Canada, most private insurers
are now reimbursing the cost of Tysabri. Generally insurance
companies
require prior authorization before they will reimburse. This
means that the insured person needs to contact his/her insurance
company in advance of purchasing the drug to ensure that the
cost will be reimbursed.
Q. How is Tysabri taken?
A. Tysabri is given via monthly intravenous infusion at a
medical facility.
Q. How long does an infusion take?
A. The actual infusion takes about one hour. After the infusion,
you will be observed for another hour to make sure you are
not having any reactions that may need medical help. The overall
visit will take longer than that because of the risk management
discussion and paperwork that will need to be processed at
the infusion site.
Q. Are infusions painful?
A. A person getting an intravenous infusion will probably
feel a sharp pain or some discomfort when the needle penetrates
the skin and vein, but then the discomfort should subside as
the infusion proceeds. There may also be discomfort when the
infusion needle is removed and the site may or may not feel
sore for a day or so.
Q. Should I switch from the therapy I'm taking now?
A. This question can only be answered through discussions
between an individual and his or her neurologist. The discussion
should
focus on how well the individual is doing on his or her current
therapy and what is currently understood about the potential
risks and benefits of Tysabri.
Q. I have relapsing MS and have never tried any of the disease-modifying
therapies. Will I be able to use Tysabri?
A. Health Canada recommends that Tysabri be used in persons
who have had inadequate response to other approved MS therapies,
or who are unable to tolerate other approved MS therapies.
This is a question you should discuss with a neurologist who
is knowledgeable about MS and familiar with your condition
and personal circumstances.
Q. Can I switch to Tysabri if I'm on another MS drug right
now?
A. Possibly. This is a matter that should be discussed with
your neurologist. The prescribing information states that Tysabri
should not be given to patients whose immune systems are compromised
or weakened. There will likely be a period of time between
the end of your current therapy and the beginning of Tysabri.
The length of time may vary depending on the type of therapy
you are currently on and the period necessary to "wash
out" the current drug from your system. If a person is
currently using an approved MS therapy such as glatiramer acetate
or interferon beta and is being switched to Tysabri, the "wash
out" period would probably be a few weeks before beginning
Tysabri infusions. If a person has recently been prescribed
Novantrone, Cytoxan, Imuran or other strong immune-suppressing
drug, the "wash out" period would be longer before
beginning Tysabri. This should be discussed with your neurologist.
The Canada-approved prescribing information does not provide
specific recommendations for "wash-out" or waiting
periods before beginning treatment with Tysabri. However, for
the post-marketing study involving persons who had been enrolled
in the original phase III studies of Tysabri (AFFIRM and SENTINEL
trials), the American FDA recommends that anyone who has been
taking an immune-modifying MS drug (such as Copaxone, Betaseron,
Avonex, or Rebif) should not begin Tysabri for two weeks after
the last dose, and that anyone who has been taking an immune-suppressing
drug (such as Novantrone, Cytoxan or Imuran) should not begin
Tysabri for three to six months after the last dose.
Q. How effective is Tysabri?
A. In a clinical trial of two years' duration, (the AFFIRM
study), 942 individuals received either Tysabri or inactive
placebo. The treated group experienced a 42 percent reduced
risk of progression of disability, a 68 percent reduction
of clinical relapses, and an 83 percent reduction in
the development
of new or newly enlarging MRI-detected brain lesions. Tysabri
also reduced the mean number of enhancing (active) MRI
lesions by 92 percent after the first and second year. These
results
were described in a published paper (The New England Journal of Medicine 2006;354:899-910 ).
A second two-year trial, (the SENTINEL study) involved
1171 individuals with relapsing MS who were on Avonex
and had
experienced at least one relapse during the previous
12 months. All participants
continued on Avonex, in combination with either Tysabri
or inactive placebo given by intravenous infusions every
four
weeks for up to 116 weeks. After one year, participants
who had Tysabri added to Avonex experienced a 54 percent
reduction
in the rate of clinical relapses compared to those on
placebo and Avonex, which was also maintained at two years
with
a 55 percent reduction.
This combination therapy resulted in a 24 percent decrease
in the risk of sustained disability progression. MRI
scans showed an 83 percent reduction in the Tysabri
plus Avonex
group in enlarging MRI lesions, and an 89 percent reduction
in lesions
showing active inflammation. Results of this study
were described in a published paper (The New England Journal of Medicine
2006;354:911-923). Two cases of progressive multifocal
leukoencephalopathy (PML),
one of which was fatal, were diagnosed in those on
combination
therapy.
Q. What is meant by the statement that Tysabri
should not be taken by people who have compromised immune systems
or who
are taking other immunosuppressive or immunomodulatory agents?
A. This means that Tysabri would not be used
in people whose immune systems are weak, such as people who
have MS plus leukemia
or lymphoma, or who are taking immune-suppressing drugs or
other MS drugs such as Avonex, Betaseron, Rebif, or Copaxone
Other drugs sometimes taken by people with MS which may weaken
their immune systems include Novantrone, Cytoxan or Imuran,
or monthly intravenous steroids.
There is no warning against the use of periodic steroids
to treat relapses in people taking Tysabri; however, the chronic
use of "pulse" or monthly steroids would possibly
weaken the immune system and therefore should probably be avoided
wherever possible.
Q. Is Tysabri better than the other available MS therapies?
A. Tysabri has not been compared head-to-head against any
other approved MS drug, and that is the only way to truly compare
the effectiveness of the MS drugs. However, generally clinicians
agree that the immunomodulatory drugs approved for use in MS
reduce the rate of relapses by about one-third. By contrast,
after two years Tysabri reduced the rate of relapses by about
two-thirds as compared to placebo. The investigators also reported
that Tysabri reduced the risk of sustained progression of disability
over those two years. There is some evidence that other approved
MS drugs also slow disease progression.
It is important to note that since MS is such a diverse disease,
there is no "one size fits all" treatment strategy.
Any decision about whether to take any of the disease-modifying
therapies should be made after careful discussion between an
individual and his or her physician of its potential risks
and benefits.
Q. Where can I call to get more information about Tysabri?
The Tysabri Care Program is a registry that supports the
safe and effective use of Tysabri. Its goals are to:
- To inform people about the risks and benefits of
Tysabri prior to treatment
- To monitor individual safety on an ongoing basis
- To provide educational materials on Tysabri for people with
MS and for health care providers
- To assist people with Tysabri reimbursement access
- To provide a network of approved infusion centres across Canada
Everyone who is enrolled in the Tysabri Care Program will
be assigned a Personal Case Manager. Personal Case Managers
will
help individuals to schedule the initial appointment at an
approved infusion centre, streamline the insurance process,
and answer any questions related to Tysabri infusions.
For more information on Tysabri or the Tysabri Care Program,
please call 1-888-827-2827.
Safety Concerns About Tysabri
Q. What is the primary safety concern regarding the use of
Tysabri?
A. A primary safety issue is the fact that three people who
had been in clinical trials involving Tysabri developed a rare
disease called PML (progressive multifocal leukoencephalopathy),
caused by a common virus called the JC virus. Two of them died,
including one woman who had been diagnosed with MS (but whose
diagnosis has since been called into question).
Q. If I take Tysabri, what are the risks that I will get
PML?
A. No one knows the true risk of getting
PML outside of the clinical trials of people taking Tysabri.
According to a study
published in The New England Journal of Medicine (The New England Journal of Medicine 2006;354:924-33), the risk
in the clinical trials population, who had taken an average
of 17.9 doses of
Tysabri, is one in one thousand.
There is not enough known about the true risk of getting
PML in people who may use Tysabri. For these and other reasons,
Biogen Idec and Elan have developed procedures for the careful
tracking of adverse events and has established a large observational
study to help evaluate the long-term safety of Tysabri.
Q. Will I be safe if I take Tysabri alone, without any other
drugs that alter the immune system?
A. No one knows. During the March 2006 advisory committee
meeting held by the American FDA about Tysabri, FDA representatives
stated that the risk of PML in those who took Tysabri alone
versus those who took Tysabri in combination with Avonex is
still unclear. That means that at this time there is insufficient
data to determine whether PML was caused by taking Tysabri
in combination with other immune-modulating drugs, or whether
PML can arise in those taking Tysabri alone.
Q. Are there any tests that can be done to know in advance
whether you are at risk for developing PML?
A. No.
Q. Are there any tests that can be done to know if you are
developing PML?
A. Yes. If a person begins to show persistent signs of new
or worsening neurological symptoms, they would likely be taken
off Tysabri. Then their doctor would likely begin tests of
the blood and spinal fluid as well as obtain an MRI scan of
the brain to help determine whether the JC virus that causes
PML is present and active.
Q. What are the signs of PML that a person using Tysabri
should look out for?
A. All of this will be clearly explained in information that
will be supplied to individuals before they begin taking Tysabri.
People will be cautioned to inform their prescribing physicians
and/or infusion nurse if they experience any new or worsening
neurological symptoms. These might include any changes in thinking,
eyesight, balance, strength and other symptoms.
Q. What is the treatment for PML?
A. There is at present no drug that has been proven to fight
the JC virus. Therefore, treatment consists of reconstituting
the immune system by withdrawing any immune-suppressing therapies.
Q. Are there risks of getting other serious infections if
I take Tysabri?
A. The clinical trials of Tysabri in MS did not reveal significant
differences in serious infections between those on active treatment
versus those on inactive placebo. However, the risks of longer-term
exposure to Tysabri are currently unknown.
Q. I read that in the US the FDA has included a "Black
Box Warning" on Tysabri's label. What does that mean?
A. According to the FDA, a Black Box Warning is " the
most serious warning placed in the labeling of a prescription
medication... Black box warnings are designed to highlight
special problems, particularly those that are serious, and
to give health care professionals a clear understanding of
a potential medical complication associated with a drug. Black
box warnings provide physicians with important insights as
to how to prescribe a drug that may be associated with serious
side effects in a way that maximizes its benefits and minimizes
its risks."
The Black Box Warning for Tysabri warns of the increased
risk of PML and the importance of monitoring people using the
drug
for any new sign or symptoms that may be suggestive of PML.
Q. Are any other side effects possible if I'm taking Tysabri?
A. Yes. These will be detailed in the materials prepared
by the drug's sponsors. In a two-year clinical trial
of Tysabri alone, some of the adverse events reported significantly
more
frequently in those on Tysabri included fatigue, allergic
reaction, and hypersensitivity reactions. In a two-year
clinical
trial
of Tysabri in combination with Avonex, adverse events
experienced
significantly more often in those on combination therapy
included anxiety, sore throat, sinus congestion and peripheral
edema
(swelling). In addition, two cases of PML, one of which
was fatal, were diagnosed in those on combination therapy.
Q. What will the MS Society of Canada do if additional
people die or experience serious side effects after
taking Tysabri?
A. The use of Tysabri carries with it the risk of developing
PML, an often fatal disease, and its use for extended
periods of time carries unknown risks. If there are
new cases,
the MS Society of Canada will disseminate information
as it becomes
available. If the risk for PML or other serious adverse
events were to significantly rise in clinical use,
The MS Society
of Canada would advocate that Health Canada take
immediate and appropriate action.
With information from the National MS Society (USA).
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