Tysabri
This summary has been prepared by the Multiple Sclerosis Society
of Canada and reviewed for accuracy by the national medical
advisor.
Tysabri (natalizumab) is a type of protein called a monoclonal
antibody that is produced from mammalian cells using recombinant
DNA techniques (a series of procedures used to join together DNA
segments). Tysabri is the first in a class of agents called selective
adhesion molecule inhibitors. In MS, inflammatory T cells enter
the central nervous system by attaching to the blood-brain barrier
with “sticky molecules”, called alpha-4 integrins.
Tysabri blocks alpha-4 integrin and prevents T cells from entering
the central nervous system, where they cause inflammation and damage
to myelin (the insulating material that protects nerves and helps
them work properly).
INDICATIONS AND USE
Health Canada approved Tysabri in 2006 for people with relapsing-
remitting MS to reduce the frequency of relapses, delay the
progression of disability and reduce the number and volume
of brain lesions seen on magnetic resonance imaging (MRI).
Tysabri is indicated as a monotherapy (not combined with
other therapies). It is generally recommended for people with
MS who have not responded adequately to other disease-modifying
therapies or who are unable to tolerate them. This is because
of an increased risk of progressive multifocal leukoencephalopathy
(PML). PML is a rare brain disease caused by the JC virus that
can cause severe disability or death. The condition usually
affects people with suppressed immune systems. Three cases
of PML were reported in clinical trials of Tysabri. There were
two deaths: one in a person with MS who was also taking Avonex,
and one in a person with Crohn’s disease who was also
taking immunosuppressants.
Since Tysabri was introduced in to the market in 2006, 95
cases of PML and 20 deaths have been reported. New data suggests
that the risk of developing PML increases with longer treatment
duration however the risk for people taking Tysabri beyond
3 years is yet to be determined. The risk of PML also increases
in people who have been treated with an immunosuppressant prior
to receiving Tysabri.
The risk of PML in people taking Tysabri has been estimated
to be 1 in 1000 (0.1%) during 18 months of treatment.18 A large-scale
study (TYGRIS) is currently investigating the risk of PML in
people receiving natalizumab monotherapy for several years.There
are no known treatments if PML occurs. The drug’s manufacturers
recommend that people who take Tysabri should enrol in the
Canadian Tysabri Care Program at 1-888-827-2827.
DOSAGE
The recommended dose of Tysabri is 300 mg every 4 weeks.
ADMINISTRATION
Tysabri is administered as an intravenous (into the vein) injection
over time (an infusion) in a specialized infusion centre
by a health professional.
SIDE EFFECTS
The most common serious side effects of Tysabri
therapy are infections and allergic reactions (rash, swelling,
difficulty breathing). Three cases of PML, including 2 deaths,
have been reported. Treatment may also be associated with infusion-related
reactions (headache, dizziness, fatigue, rash). Less common
side effects include anemia, cough, muscle cramps and depression.
Treatment with Tysabri (natalizumab) has been associated
with an increased risk of progressive multifocal leukoencephalopathy
(PML). PML can cause disability or death. Healthcare professionals
must monitor people on Tysabri for any new sign or symptom
that may be suggestive of PML. Tysabri should be withheld
immediately at the first sign or symptom suggestive of PML.
NEUTRALIZING ANTIBODIES
Some people taking Tysabri develop “neutralizing” antibodies
(NAb). Persistent NAbs to Tysabri are associated with a lesser
treatment effect and an increased risk of hypersensitivity
reactions and/or infusion-related reactions (rigors, nausea/vomiting
and flushing). Antibody testing should be performed if NAbs
are suspected. The occurrence of NAbs may be transient. If
they persist, discontinuation of treatment should be considered.
DRUG IDENTIFICATION NUMBER (DIN)
02286386
COST REIMBURSEMENT
Private and group health plans may provide some coverage for
people who meet the prescribing criteria. Financial assistance
through the Canadian Tysabri Care Program may be available
to people who cannot afford the drug. For more information,
call 1-888-827-2827.
REIMBURSEMENT CRITERIA
Assistance with treatment costs varies among provinces and
private insurance companies. In most cases, to be reimbursed
an individual must have active relapsing-remitting MS (at
least 1 or 2 MS attacks in the 1 or 2 years prior to starting
treatment) and be ambulatory. The exact definition of “ambulatory” varies
among the provincial drug programs and private/group insurance
plans. For more information on reimbursement, please contact
your nearest division office at 1-800-268-7582, or your provincial
government program office (telephone numbers are listed under Provincial
Drug Programs - Contact Information).
CLINICAL TRIAL RESULTS
Clinical Trials
Note: Numerous clinical trials have been conducted for each
of the disease-modifying therapies. The clinical trials included
in this summary are those that have led to Health Canada approval
for the therapy to be prescribed and sold in Canada, or that
have led provincial health ministries to agree to reimburse
the cost of that therapy or to make a significant change to
the reimbursement criteria.
Clinical Trials in Relapsing-Remitting MS
AFFIRM Study
AFFIRM: Natalizumab Safety and Efficacy in Relapsing Remitting
Multiple Sclerosis
This clinical trial involved 942 people with relapsing-remitting
MS who were treated with either Tysabri or placebo (a treatment
that has no active medication) for over 3 years. Results of
the study showed that Tysabri reduced the risk of sustained
progression of disability compared to placebo. Tysabri reduced
the annual relapse rate by 68% compared to placebo and also
reduced the number of brain lesions on MRI.1 [Polman
et al. N Engl J Med 2006; 354: 899-910]
SENTINEL Study
SENTINEL: Safety and Efficacy of Natalizumab in Combination
with Interferon
Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis
This study examined whether the combination of Tysabri and
Avonex was safe and more effective than Avonex alone in people
who were continuing to have relapses while on Avonex monotherapy.
A total of 1,171 people taking Avonex for relapsing-remitting
MS were treated with Tysabri or a placebo infusion for up to
120 weeks. The study was stopped one month early after two
cases of PML had been reported. At 1 and 2 years, the annual
relapse rate was reduced about 54% with the Tysabri/Avonex
combination compared to Avonex alone. Combination therapy also
reduced the probability of disease progression at 2 years,
and reduced the number of brain lesions seen on MRI compared
to Avonex alone.2 [Rudick
et al. N Engl J Med 2006; 354: 911-923]
CURRENT CLINICAL TRIALS
A number of clinical trials involving the five disease-modifying
therapies are underway. The studies are examining the effectiveness
at different doses and the possible benefits of combining
therapies. For more information about clinical trials, please
visit the MS Society of Canada website by going to www.mssociety.ca and
click on Research.
PHARMACEUTICAL COMPANY
Biogen Idec Canada Inc. 3 Robert Speck Parkway Mississauga,
Ontario L4Z 2G5
FURTHER INFORMATION
Further information for persons with MS is available through
the Canadian Tysabri Care Program at 1-888-827-2827.
Back to top
References
- Polman
CH, O’Connor
PW, Havrdova E, et al. A randomized, placebo-controlled trial
of natalizumab for relapsing multiple sclerosis. N Engl J Med
2006; 354: 899-910.
- Rudick
RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon
beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;
354: 911-923.
The drug information contained in this publication
has been obtained from the manufacturers’ product monographs.
Consult the package insert for more
detailed information about the product’s indications, contraindications,
medical use and side effects. If you are taking any of the medications
listed above, do not change the dose or stop taking your medication
without consulting your physician first.
Avonex® is a registered trademark of Biogen Idec Canada Inc.
Betaplus® is a registered trademark of Bayer HealthCare Pharmaceuticals
Betaseron® is a registered trademark of Bayer HealthCare Pharmaceuticals
Copaxone® is a registered trademark of Teva Neuroscience
Extavia® is a registered trademark of Novartis Pharmaceuticals
Canada Inc.
Gilenya® is a registered trademark of Novartis Pharmaceuticals
Canada Inc.
Gilenya GO Program® is a registered trademark of Novartis Pharmaceuticals
Canada Inc.
MS Alliance® is a registered trademark Biogen IDEC Canada
Rebif® is a registered trademark of EMD Serono Canada Inc.
Multiple Support Program® is a registered trademark of EMD Serono
Canada Inc.
Shared Solutions® is a registered trademark of Teva Neuroscience
Tysabri® is a registered trademark of Biogen Idec Canada Inc.
and Elan Pharmaceuticals
Tysabri Care Program® is a registered trademark of Biogen Idec
Canada Inc. and Elan Pharmaceuticals
© 2010, National Multiple Sclerosis Society
This resource has been adapted by the Multiple Sclerosis Society of Canada with
permission of the National Multiple Sclerosis Society (USA).
Back to top
|
