Modifying the Disease Course
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Five drug therapies are approved for the treatment of some forms
of multiple sclerosis (MS) in Canada. Four of these medications — Avonex®,
Betaseron®, Copaxone® and Rebif® — are
immune modulating medications. The fifth — Tysabri® — is
a selective adhesion molecule inhibitor. In large clinical trials,
all of these drugs have been found to have a direct influence
on altering the course of MS. They are sometimes referred to
collectively as disease-modifying therapies.
The following summary provides brief information about each drug.
It is not intended to be a comparison of the drugs to each other
or to endorse or recommend any specific therapy. The summary
has been prepared by the Multiple Sclerosis Society of Canada
and reviewed for accuracy by the national medical advisor.
For more information about these therapies or for other information
about MS management, please contact your physician, or the nearest
Multiple Sclerosis Society of Canada division office at 1-800-268-7582.
The cost of disease-modifying therapies for MS varies widely,
from about $20,000 to $40,000 per year. The actual cost will
depend on the treatment selected, the dosage, provincial pricing,
pharmacy or clinic costs, dispensing fees, etc.
The MS Society is aware that the level of reimbursement and access
criteria vary from province to province and is working to ensure
that people who could benefit from treatment have access. For
more information on these topics, contact your nearest division
office at 1-800-268-7582.
Production and distribution of MS Disease-Modifying Therapies
in Canada were made possible through an unrestricted educational
grant from Biogen Idec Canada.
Avonex
Avonex (interferon beta-1a) is a type of protein called a beta-interferon
that is produced from mammalian cells using recombinant DNA techniques
(a series of procedures used to join together DNA segments).
Beta-interferon occurs naturally in the human body in response
to initiating factors such as viruses. In MS, the main effects
of Avonex are to block the activity of certain immune system
cells and to reduce the passage of these immune cells into 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 Avonex in 1998 for
the treatment of relapsing forms of MS to slow the progression
of disability, decrease the frequency of MS attacks, and reduce
the number and volume of brain lesions seen on magnetic resonance
imaging (MRI). MRI is a powerful tool that provides images of
the brain, spinal cord, or other areas of the body. It is often
used in MS to identify areas of inflammation.
Health Canada approved Avonex in 2003 for the treatment of people
who have experienced a single event suggestive of MS (called
clinically isolated syndrome, or CIS), so as to delay the onset
of clinically definite MS and to decrease the number and volume
of active brain lesions on MRI. Before Avonex is initiated, people
with CIS must have brain lesions on MRI and other possible diagnoses
must be ruled out.
Avonex is not approved for use in primary-progressive MS. This
less common (10 to 15% at time of diagnosis) type of MS is characterized
by slowly progressive worsening of MS from the beginning with
no clear relapses or remissions.
DOSAGE The recommended dose of Avonex is 30 mcg once per week.
ADMINISTRATION Avonex is self-injected once per week into the
muscle (intramuscularly). The medication is now available as
a pre-filled syringe.
SIDE EFFECTS The most common side effects of Avonex therapy include
flu-like symptoms (fatigue, chills, fever, muscle aches, and
sweating). Most of these symptoms tend to improve over time.
Less common side effects include injection site reactions (swelling,
redness, discolouration, and pain), some liver, blood and thyroid
problems, allergic reactions and depression.
NEUTRALIZING ANTIBODIES Some people taking a beta-interferon
therapy develop neutralizing anti-bodies (NAb). It is not known
if NAbs completely “neutralize” the clinical benefits
of therapy. Some research has found that a higher NAb level may
be associated with a lesser treatment effect. The level of NAbs
associated with the use of Avonex is lower than that seen during
treatment with the other two beta-interferons. Studies are continuing
in this area, as is the development of a standardized NAb test.
DRUG IDENTIFICATION NUMBER (DIN) 02237770; 02269201 for the pre-filled
syringe
COST REIMBURSEMENT Much of the cost can be reimbursed through
private and group health plans for people who meet the prescribing
criteria, and through provincial drug programs for individuals
who meet the prescribing criteria.
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. In Ontario and Quebec, Avonex can be reimbursed for persons
at high risk of developing MS who meet specific criteria. 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 For more information, Provincial Drug Programs).
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. For
inclusion here, the clinical trial must have been published in
a peer-reviewed scientific journal.
Clinical Trials in Relapsing-Remitting MS
MSCRG Study
MSCRG: Multiple Sclerosis Collaborative Research Group Study
In this clinical trial, 301 people with relapsing-remitting MS
were treated with either Avonex at a dose of 30 mcg once per
week or placebo (a treatment that has no active medication) for
over 2 years. Results of the study showed that Avonex delayed
the time to sustained progression of disability compared to placebo.
The proportion of patients who progressed was reduced 37% (21.9%
vs. 34.9%). Avonex reduced the annual attack rate by 18-32% compared
to placebo and also reduced the number of brain lesions on MRI.1 [Jacobs et al. Ann Neurology 1996; 39: 285-294]
Clinical Trials: Single Event Suggestive of MS
CHAMPS Study
CHAMPS: Controlled High-Risk Subjects Avonex Multiple Sclerosis
Prevention Study
This study examined whether Avonex could reduce conversion to
clinically definite MS in people who had a single neurological
event suggestive of MS (an event involving the optic nerve, brain
stem/cerebellum, or spinal cord) but who had not been diagnosed
with MS. A total of 383 persons were treated with Avonex or placebo
for up to 3 years. Treatment with Avonex resulted in a 44% reduction
in the chance of having a second MS attack over the three-year
period.2 [Jacobs et al. N Engl J Med 2000; 343: 898-904]
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 3 Robert Speck Parkway
Mississauga, Ontario L4Z 2G5
FURTHER INFORMATION Further information for persons with MS is
available through MS Alliance at 1-888-456-2263.
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Betaseron
Betaseron (interferon beta-1b) is a beta-interferon that is produced
from bacterial cells using recombinant DNA techniques (a series
of procedures used to join together DNA segments). Beta-interferon
is a protein that occurs naturally in the human body in response
to initiating factors such as viruses. In MS, the main effects
of Betaseron are to block the activity of certain immune system
cells and to reduce the passage of these immune cells into 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 Betaseron in 1995
for the treatment of people with relapsing-remitting MS who are
ambulatory (able to walk) to reduce the frequency of attacks.
Relapsing-remitting MS is characterized by recurrent attacks
followed by complete or incomplete recovery.
Betaseron was approved by Health Canada in 1999 for the treatment
of secondary-progressive MS to slow the progression of disability
and to reduce the frequency of MS attacks. About one-half of
people with relapsing-remitting MS start to worsen within 10
years of diagnosis, with the possibility of increasing levels
of disability and continued relapses. This is known as secondary-progressive
MS.
Health Canada has also approved Betaseron for the treatment of
people who have experienced a single event suggestive of MS (called
clinicallyisolated syndrome, or CIS) accompanied by at least
two lesions on MRI to delay the progression to clinically definite
MS. Before Betaseron is initiated, alternative diagnoses must
be ruled out.
Betaseron is not approved for use in primary-progressive MS.
This less common (10 to 15% at time of diagnosis) type of MS
is characterized by slowly progressive worsening of MS from the
beginning with no clear relapses or remissions.
DOSAGE The recommended dose of Betaseron for both relapsing-remitting
and secondary-progressive MS is 250 mcg every other day.
ADMINISTRATION Betaseron is self-injected every other day under
the skin (subcutaneously). Betaseron is available in a diluent
pre-filled syringe. A diluent is a diluting agent. With Betaseron,
the syringes are pre-filled with a salt-water solution to mix
with the active medication, which is in a powder form. Betaseron
does not require refrigeration.
SIDE EFFECTS The most common side effects of Betaseron therapy
include flu-like symptoms (fatigue, chills, fever, muscle aches,
and sweating) and injection site reactions (swelling, redness,
discolouration, and pain). Most of these symptoms tend to improve
over time.
Less common side effects include some liver, blood and thyroid
problems, as well as allergic reactions and depression.
NEUTRALIZING ANTIBODIES Some people taking a beta-interferon
therapy develop neutralizing anti-bodies (NAb). It is not known
if NAbs completely “neutralize” the clinical benefits
of therapy. Some research has found that a higher NAb level may
be associated with a lesser treatment effect. Studies are continuing
in this area, as is the development of a standardized NAb test.
DRUG IDENTIFICATION NUMBER (DIN) 02169649
COST REIMBURSEMENT Much of the cost can be reimbursed through
private and group health plans for people who meet the prescribing
criteria, and through provincial drug programs for individuals
who meet the prescribing criteria.
In addition, a program called Bridging the Gap is available to
provide financial help for people with insurance or government
program copayments or deductibles. For more information, call
1-800-977-2770.
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
For more information, Provincial Drug Programs).
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. For inclusion here, the clinical trial must have been
published in a peer-reviewed scientific journal.
Clinical Trials in Relapsing-Remitting MS
Interferon Beta Multiple Sclerosis Study Group
In this clinical trial, 372 people with relapsing-remitting MS
received Betaseron at a dose of either 1.6 MIU or 8 MIU, or placebo
(a treatment that has no active medication) for 2 years. Compared
to placebo, Betaseron reduced the annual attack rate by about
30%.3 [The IFNB Multiple Sclerosis Study Group. Neurology 1993;
43: 641-643]. Betaseron also reduced disease activity, as measured
by magnetic resonance imaging (MRI), by 80% compared to placebo.4 [Paty & Li. Neurology 1993; 43(4): 662-667] MRI is a powerful
tool that provides images of the brain, spinal cord, or other
areas of the body. It is often used in MS to identify areas of
inflammation.
Clinical Trials in Secondary-Progressive MS
European Study in Secondary-Progressive MS
In this study, 718 people with secondary-progressive MS received
either Betaseron or placebo for up to 3 years. Compared to placebo,
Betaseron delayed progression of disability for 9-12 months.
Betaseron also reduced the attack rate by 31%.5 [European Study
Group on Interferon b-1b in Secondary Progressive MS. Lancet
1998; 352: 1491-1497]. A separate analysis of MRI results found
that Betaseron reduced the accumulation of new lesions compared
to placebo.6 [Miller et al. Ann Neurol 1999; 46: 850–859]
The final analysis (mean 35 month follow-up) of this study confirmed
the benefits of Betaseron over placebo with respect to progression
and relapses.7 [Kappos et al. Neurology 2001; 57: 1969- 1975]
North American Study in Secondary-Progressive MS
The North American study of Betaseron involved 939 individuals
with secondary-progressive MS. In this trial, treatment with
Betaseron failed to show a significant difference in the time
to progression compared to placebo, although there were improvements
in relapses and MRI brain lesions.8 [North American Study Group
on Interferon Beta-1b in Secondary Progressive MS. Neurology
2004; 63: 1788-1795]
Clinical Trials: Single Event Suggestive of MS
BENEFIT trial
BENEFIT: Betaferon in Newly Emerging Multiple Sclerosis for Initial
Treatment This study examined whether Betaseron could reduce
conversion to clinically definite MS in people who had a first
clinical event suggestive of MS (an event involving the optic
nerve, brain stem/cerebellum, or spinal cord) and at least two
clinically silent brain lesions on MRI. A total of 468 were treated
with Betaseron or placebo for up to 2 years. The probability
of developing clinically definite MS over 2 years was 45% with
placebo compared to 28% with Betaseron, for an absolute risk
reduction of 17% and a relative risk reduction of 38%.9 [Kappos
et al. Neurology 2006; 67: 1242-1249]
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 Bayer HealthCare Pharmaceuticals 77 Belfield
Rd. Toronto, Ontario M9W 1G6
FURTHER INFORMATION Further information for persons with MS is
available through MS Pathways at 1-800 977-2770.
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Copaxone
Copaxone (glatiramer acetate) is a synthetic protein made up
of a combination of four amino acids that chemically resemble
a component of myelin (the insulating material that protects
nerves and helps them work properly). Copaxone induces the production
of immune cells that are less damaging to myelin.
INDICATIONS AND USE Health Canada approved Copaxone in 1997 for
the treatment of people with relapsing-remitting MS who are ambulatory
(able to walk) to reduce the frequency of attacks. Relapsing-remitting
MS is characterized by recurrent attacks followed by complete
or incomplete recovery.
Copaxone is not approved for use in primary-progressive MS. This
less common (10 to 15% at time of diagnosis) type of MS is characterized
by slowly progressive worsening of MS from the beginning with
no clear relapses or remissions.
DOSAGE The recommended dose of Copaxone is 20 mg per day.
ADMINISTRATION Copaxone is self-injected every day under the
skin (subcutaneously). Copaxone is available in pre-filled syringes
that are ready for injection.
SIDE EFFECTS The most common side effects of Copaxone therapy
are injection-site reactions. Less common side effects include
some of the following symptoms immediately after an injection:
flushing, chest pain, palpitations (irregular beating of the
heart), anxiety, and difficulty breathing. However, these symptoms
are usually temporary and do not require specific treatment.
NEUTRALIZING ANTIBODIES Copaxone induces the development of antibodies
(not neutralizing anti- bodies) but the significance of this
is not known.
DRUG IDENTIFICATION NUMBER (DIN) 02245619
COST REIMBURSEMENT Much of the cost can be reimbursed through
private and group health plans for people who meet the prescribing
criteria, and through provincial drug programs for individuals
who meet the prescribing criteria.
In addition, a program called the Copaxone Assistance Program
is available to provide financial help for people with insurance
or government program co-payments or deductibles. For more information,
contact Shared Solutions at 1-800-283-0034.
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
For more information, Provincial Drug Programs).
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. For inclusion here, the clinical trial must have been
published in a peer-reviewed scientific journal.
Clinical Trials in Relapsing-Remitting MS
Phase III Trial of Copaxone
In this clinical trial, 251 persons with relapsing-remitting
MS were randomized to receive either Copaxone or placebo for
2 years. Study participants treated with Copaxone showed a 29%
reduction in relapses compared to placebo.10 [Johnson et al.
Neurology 1995; 45: 1268-1276]
European/Canadian MRI Study
This study examined the effect of Copaxone on disease activity
in 239 persons with relapsing-remitting MS. Patients were monitored
by magnetic resonance imaging (MRI). MRI is a powerful tool that
provides images of the brain, spinal cord, or other areas of
the body. It is often used in MS to identify areas of inflammation.
Results of the study showed that treatment with Copaxone was
associated with fewer MRI brain lesions than was placebo. The
relapse rate was also reduced by onethird with Copaxone compared
to placebo.11 [Comi et al. Neurology 2001; 49: 290-297]
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 Teva Neuroscience 999 Boul. de Maisonneuve
W., Suite 550 Montreal, Quebec H3A 3L4
FURTHER INFORMATION Further information for persons with MS is
available by contacting Shared Solutions at 1-800-283-0034.
back to top
Rebif
Rebif (interferon beta-1a) is a beta-interferon that is produced
from mammalian cells using recombinant DNA techniques (a series
of procedures used to join together DNA segments). Beta-interferon
is a protein that occurs naturally in the human body in response
to initiating factors such as viruses. In MS, the main effects
of Rebif are to block the activity of certain immune system cells
and to reduce the passage of these immune cells into 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 Rebif in 1998 for
the treatment of relapsing forms of MS (in which persons still
experience recurrent attacks, such as relapsing-remitting MS
and secondary-progressive MS with relapses) to reduce the number
and severity of attacks, slow the progression of physical disability,
reduce the need for steroids and the number of hospitalizations
due to MS, and to reduce the number of brain lesions seen on
magnetic resonance imaging (MRI). MRI is a powerful tool that
provides images of the brain, spinal cord, or other areas of
the body. It is often used in MS to identify areas of inflammation.
Relapsing-remitting MS is characterized by recurrent attacks
followed by complete or incomplete recovery. About one-half of
people with relapsing- remitting MS start to worsen within 10
years of diagnosis, with the possibility of increasing levels
of disability and continued relapses. This is known as secondary-progressive
MS.
Rebif is not approved for use in primary-progressive MS. This
less common (10 to 15% at time of diagnosis) type of MS is characterized
by slowly progressive worsening of MS from the beginning with
no clear relapses or remissions.
DOSAGE The usual dose of Rebif is 44 mcg three times per week.
It is also available in a dose of 22 mcg three times per week.
ADMINISTRATION Rebif is self-injected three times per week under
the skin (subcutaneously). Rebif is available in a pre-filled
syringe.
SIDE EFFECTS The most common side effects of Rebif therapy include
flu-like symptoms (fatigue, chills, fever, muscle aches, and
sweating) and injection site reactions (swelling, redness, discolouration,
and pain). Most of these symptoms tend to improve over time.
Less common side effects include some liver, blood and thyroid
problems, as well as allergic reactions and depression.
NEUTRALIZING ANTIBODIES Some people taking a beta-interferon
therapy develop neutralizing anti-bodies (NAb). It is not known
if NAbs completely “neutralize” the clinical benefits
of therapy. Some research has found that a higher NAb level may
be associated with a lesser treatment effect. Studies are continuing
in this area, as is the development of a standardized NAb test.
DRUG IDENTIFICATION NUMBER (DIN) 02237319 for the 22 mcg dose
02237320 for the 44 mcg dose
COST REIMBURSEMENT Much of the cost can be reimbursed through
private and group health plans for people who meet the prescribing
criteria, and through provincial drug programs for individuals
who meet the prescribing criteria.
In addition, a program called the Multiple Support Program is
available to assist persons in obtaining funding for Rebif therapy.
For more information on this program, contact 1-888-677-3243
(English) or 1-877-777-3243 (French).
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
For more information, Provincial Drug Programs).
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 to provincial health ministries agreeing to reimburse
the cost of that therapy or to make a significant change to the
reimbursement criteria. For inclusion here, the clinical trial
must have been published in a peer-reviewed scientific journal.
Clinical Trials in Relapsing-Remitting MS
PRISMS Study PRIS
MS: Prevention of Relapses and Disability by Interferon beta-1a
Subcutaneously in Multiple Sclerosis
The PRISMS study compared the effects of Rebif at two doses (44
mcg and 22 mcg, three times per week) with placebo (a treatment
that has no active medication) in 560 persons with relapsing-remitting
MS. At 2 years, both doses of Rebif were shown to be more effective
than placebo in reducing the number and frequency of relapses.
With the higher dose of Rebif, the number of relapses was reduced
by about one-third. Rebif also delayed the progression of disability,
and a larger proportion of people were relapse-free with treatment
compared to placebo.12 [PRISMS Study Group. Lancet 1998; 352:
1498-1504] A separate report on MRI results found that Rebif
reduced the number of brain lesions compared to placebo.13 [Li
et al. Ann Neurol 1999; 46: 197-206]
Clinical Trials: Single Event Suggestive of MS
ETOMS Study
ETOMS: Effect of Early Treatment on Conversion to Definite MS
This study examined the effects of Rebif on the occurrence of
MS attacks in 308 persons who were at risk of developing clinically
definite MS, but who were not yet diagnosed with the disease.
After 2 years of treatment, fewer persons in the Rebif group
developed clinically definite MS (34%) compared to those in the
placebo group (45%), which represents a 24% reduction in risk.
Rebif was also found to have a positive effect on the relapse
rate and MRI measures compared to placebo.14 [Comi et al. Lancet
2001; 357: 1576-1582]
Clinical Trials in Secondary-Progressive MS
SPECTRIMS Study
SPECTRIMS: Secondary-Progressive Efficacy Clinical Trial of Recombinant
Interferon beta-1a in MS
In the SPECTRIMS study, 618 persons with secondary-progressive
MS were treated with either Rebif or placebo for 3 years. The
study found that Rebif did not slow disease progression in people
with secondaryprogressive MS. Rebif treatment was associated
with fewer relapses.15 [SPECTRIMS Study Group. Neurology 2001;
56: 1496-1504] Rebif was also associated with fewer brain lesions
as measured by MRI.16 [Li et al. Neurology 2001; 56: 1505-1513]
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 EMD Serono Canada Inc. 1075 North Service
Rd W., Suite 100 Oakville, Ontario L6M 2G2
FURTHER INFORMATION Further information for persons with MS is
available through the Multiple Support Program at 1-888-677-3243
(English) or 1-877-777-3243 (French).
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Tysabri
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). MRI is a powerful tool that provides images of
the brain, spinal cord, or other areas of the body. It is often
used in MS to identify areas of inflammation.
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.
The risk of PML in people taking Tysabri has been estimated to
be 1 in 1000 (0.1%) during 18 months of treatment.17 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.
Tysabri is not approved for use in primary-progressive MS. This
less common (10 to 15% at time of diagnosis) type of MS is characterized
by slowly progressive worsening of MS from the beginning with
no clear relapses or remissions.
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.
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.
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
For more information, Provincial Drug Programs).
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. For inclusion here, the clinical trial must have been
published in a peer-reviewed scientific journal.
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.18 [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.19 [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.
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References
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Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular
interferon beta-1a for disease progression in relapsing multiple
sclerosis.
The Multiple Sclerosis Collaborative Research Group (MSCRG).
Ann Neurology 1996; 39: 285-294.
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Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon
beta-1a therapy initiated during a first demyelinating event
in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000;
343: 898-904.
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The IFNB Multiple Sclerosis Study Group. Interferon beta-1b
is effective in relapsing-remitting multiple sclerosis. I.
Clinical results of a multicenter, randomized, double-blind,
placebo-controlled trial. Neurology 1993; 43: 641-643.
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Paty DW, Li DK. Interferon beta-1b is effective in relapsing-remitting
multiple sclerosis. II. MRI analysis results of a multicenter,
randomized, double-blind, placebo-controlled trial. UBC MS/MRI
Study Group and the IFNB Multiple Sclerosis Study Group.
Neurology 1993; 43: 662-667.
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European Study Group on Interferon Beta-1b in Secondary-Progressive
MS. Placebo-controlled multicentre randomised trial of interferon
beta-1b in treatment of secondary-progressive multiple sclerosis.
Lancet 1998; 352: 1491-1497.
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Miller DH, Molyneux PD, Barker GJ, et al. Effect of interferon-beta1b
on magnetic resonance imaging outcomes in secondary progressive
multiple sclerosis: results of a European multicenter,
randomized, double-blind, placebo-controlled trial. Ann Neurol
1999; 46: 850–859.
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Kappos L, Polman C, Pozzilli C, et al. Final analysis of
the European multicenter trial on IFNbeta-1b in secondary-progressive
MS. Neurology 2001; 57: 1969-1975.
-
North American Study Group on Interferon Beta-1b in Secondary
Progressive MS. Interferon beta-1b in secondary progressive
MS: results from a 3-year controlled study. Neurology 2004;
63: 1788-1795
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Kappos L, Polman CH, Freedman MS, et al. Treatment with
interferon beta-1b delays conversion to clinically definite
and McDonald
MS in patients with clinical isolated syndromes. Neurology
2006; 67: 1242-1249.
-
Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces
relapse rate and improves disability in relapsing-remitting
multiple sclerosis: results of a phase III multicenter, double-blind
placebocontrolled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45: 1268-1276.
-
Comi G, Filippi M, Wolinsky JS. European/ Canadian multicenter,
double-blind, randomized, placebocontrolled study of the
effects of glatiramer acetate on magnetic resonance imaging-measured
disease activity and burden in patients with relapsing multiple
sclerosis. European/ Canadian Glatiramer Acetate Study Group.
Ann Neurology 2001; 49: 290-297.
-
PRISMS Study Group. Randomised double-blind placebo-controlled
study of interferon beta-1a in relapsing/remitting multiple
sclerosis. Lancet 1998; 352: 1498-1504.
-
Li DKB, Paty DW, and the UBC MS/MRI Analysis Research
Group and the PRISMS Study Group. Magnetic resonance imaging
results of the PRISMS trial: a randomized, double-blind, placebo-controlled
study of interferon-beta1a in relapsing-remitting multiple
sclerosis. Ann Neurol 1999; 46: 197-206.
-
Comi G, Filippi M, Barkhof F, et al. Effect of early interferon
treatment on conversion to definite multiple sclerosis: a
randomised study Lancet 2001; 357: 1576-1582.
-
SPECTRIMS Study Group. Randomized controlled trial of
interferon beta-1a in secondary progressive MS. Neurology
2001; 56: 1496-1504.
-
Li DKB, Zhao GJ, Paty DW, et al. Randomized controlled
trial of interferon beta-1a in secondary progressive MS: MRI
results.
Neurology 2001; 56: 1505-1513.
-
Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation
of patients treated with natalizumab for progressive multifocal
leukoencephalopathy. N Engl J Med 2006; 354: 924-933.
-
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.
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For more information
PROVINCIAL DRUG PROGRAMS
Alberta
Alberta Blue Cross: 1-800-661-6995
British Columbia
Pharmacare Special Authority Process: 1-800-554-0250
Manitoba
Pharmacare Exceptional Drug Status: (204) 788-6388
New Brunswick
MS Prescription Drug Program: 1-800-332-3692 or (506) 867-4515
Newfoundland and Labrador
Prescription Drug Program: (709) 729-6507
Nova Scotia
Special MS Therapy Program MS Clinic: (902) 422-7817
Ontario
Ontario Drug Benefits Section 8 Mechanism: 1-866-811-9893 or
(416) 327-8109
Prince Edward Island
MS Program: 1-877-577-3737 or (902) 368-4947
Québec
Régie de l’assurance-maladie du Québec (RAMQ) — service
de l’expertise pharmaceutique:
1-800-561-9749 or (514) 864-3411
Saskatchewan
MS Drugs Program: (306) 655-8400
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