| |
Avonex® |
Betaseron® |
Copaxone® |
Rebif® |
| Manufacturer |
Biogen |
Berlex |
Teva |
Serono |
| Generic
Name |
Interferon
beta-1a |
Interferon
beta-1b |
Glatiramer
acetate |
Interferon
beta-1a |
| Indications |
For
the treatment of relapsing forms of MS, to slow the accumulation of physical
disability and decrease the frequency of clinical exacerbations |
For
use in patients with relapsing- remitting MS, to reduce the frequency of
clinical exacerbations |
For
use in patients with relapsing-remitting MS, to reduce the frequency of
relapses |
For
the treatment of relapsing forms of MS, to decrease the frequency of clinical
exacerbations, and delay accumulation of physical disability |
| Contraindications |
Hypersensitivity
to natural or recombinant interferon beta, human albumin, or any other
component of the formulation |
Hypersensitivity
to natural or recombinant interferon beta, human albumin USP, or any other
component of the formulation |
Hypersensitivity
to glatiramer acetate or mannitol |
Hypersensitivity
to natural or recombinant interferon, human albumin or any other component
of the formulation |
| Warnings |
Depression
and suicide have been reported to occur in patients receiving an agent
related to Avonex called interferon alfa. Patients treated with Avonex
who exhibit depression should be monitored closely |
Depression
and suicide have been reported to occur in patients receiving an agent
related to Betaseron called interferon alfa. Patients treated with Betaseron
who exhibit depression should be monitored closely.
Injection site necrosis has been
reported, usually within the first 4 months of therapy. Time to healing
of the lesion varies and may be associated with scarring |
Copaxone
should not be administered intravenously |
Depression
and suicide have been reported in patients receiving interferon compounds,
including Rebif. Patients receiving Rebif who exhibit depression should
be monitored closely.
Rebif should be used with caution
in patients with active liver disease, alcohol abuse, SGPT>2.5 times the
upper limits of normal, or a history of significant liver disease
Allergic reactions including anaphylaxis,
skin rash and, urticaria have been reported, with no clear association
to dose or duration of treatment. |
| |
Avonex |
Betaseron |
Copaxone |
Rebif |
| Precautions |
Should
be used cautiously in patients with pre-existing seizure disorders, angina,
congestive heart failure, or arrhythmia
Use of aseptic technique is required
to administer this agent |
Use
of aseptic technique is required to administer this agent |
Use of aseptic
technique is required to administer this agent. There is a possibility
that this agent will interfere with immune function. The continued long-term
use has not been evaluated.
|
Should
be used cautiously in patients with pre-existing seizure disorders. Regular
monitoring for leukopenia and thyroid abnormalities is recommended
Use of aseptic technique is required
to administer this agent |
| Drug
Interactions |
Drug
interactions have not been fully evaluated |
Drug
interactions have not been fully evaluated |
Drug
interactions have not been fully evaluated |
Drug
interactions have not been fully evaluated. Close monitoring for neutropenia
and leukopenia is recommended when myelosuppressive agents are used concomitantly |
| Common
Adverse Reactions |
Flu
like symptoms, such as muscle aches, fever, chills, and asthenia.
Laboratory abnormalities include
a decrease in red blood cells (anemia) |
Injection
site reactions, such as inflammation, pain, necrosis; flu like symptoms,
such as fever, chills, muscle aches, sweating. Laboratory abnormalities
include a decrease in white blood cell count and increases in total bilirubin
and SGPT. Menstrual irregularities |
Injection
site reactions, such as redness, itching, pain, welt, inflammation
and induration. Post-injection reactions:
consisting of flushing, chest
pain, palpitations, anxiety, dyspnea,
throat constriction and urticaria.
Transient chest pain. |
Depression,
injection site reactions, flu like symptoms, and abdominal pain. Laboratory
abnormalities include elevation of liver enzymes and decreases in leukocytes
and platelets |
| |
Avonex |
Betaseron |
Copaxone |
Rebif |
| Dosage/
Administration |
30
mcg injected intramuscularly once a week |
250
mcg injected subcutaneously every other day |
20
mg injected subcutaneously every day |
44
mcg injected subcutaneouly 3 times per week |
| How
Supplied |
Single-use
vial containing 33 mcg of interferon beta-1a, 16.5 mg human albumin, 6.4
mg sodium chloride, along with sodium phosphate. A separate vial is provided
containing 1.1 ml sterile water for injection to be used as a diluent |
Single-use
3 ml vial containing 300 mcg Interferon beta-1b, 15 mg human albumin, and
15 mg dextrose. A separate vial is provided containing 2 ml of sodium chloride
to be used as a diluent |
Single-use
2 ml vial containing 20 mg glatimer acetate and 40 mg mannitol. A separate
vial is provided containing 1.1 ml sterile water for injection to be used
as a diluent |
Single-use,
pre-filled syringes containing 44 mcg of interferon beta-1a. Single-use,
pre-filled syringes containing 22 mcg of interferon beta-1a are also available
in a Starter Pack |
| Storage |
Store
under refrigeration |
Store
under refrigeration |
Refrigerate
unreconstituted drug. Diluent may be kept at room temperature |
Store
under refrigeration |
| Shelf
Life |
Reconstituted
product should be refrigerated and used within 6 hours. If unreconstituted
product cannot be refrigerated it can be stored at 25 degrees C (77 degrees
F) for up to 30 days |
Reconstituted
product should be refrigerated and used within 3 hours. If unreconstituted
product cannot be refrigerated it should be kept at below 30 degrees C
(86 degrees F) and used within 7 days
A new formulation with room temperature
stability will be available in May 2002 |
Unreconstituted
product can be kept at room temperature for up to 1 week |
Rebif
contains no preservatives. It should not to be used beyond the expiration
date printed on packages |
| Nurse
Counseling |
MS
ActiveSource™ offers information literature and videos on living with MS,
Monday - Friday, 8:30 AM to 8:00 PM
1-800-456-2255 |
MS
Pathways™ offers 24-hour access to the Nurse Hotline staffed by experienced
MS nurses
1-800-788-1467 |
Shared
Solutions™ offers confidential nurse counseling Monday - Friday, 7:00 AM
to 10:00 PM (CT)
1-800-887-8100 |
MS
LifeLines offers support from specialists Monday - Friday from 8am to 8pm
EST
1-877-44-REBIF |
| Clinical
Trials |
Clinical
trials that examine the efficacy of drugs used for the treatment of relapsing-remitting
multiple sclerosis generally compare one drug with placebo over a 2-year
period. It is difficult to make comparisons between trials because of differences
in the dosing regimens used, degree of illness of patients enrolled, and
the tests used to measure drug effect. It is because of these differences
that each of these trials must be viewed independently.
An example of a clinical trial involving
each of the agents available to treat relapsing remitting multiple sclerosis
follows: |
| |
Avonex |
Betaseron |
Copaxone |
Rebif |
| Number
of Patients Enrolled |
301 |
372 |
251 |
560 |
| Dosing
Regimen Used |
6
million IU (30 mcg) or placebo was administered intramuscularly once weekly |
50
mcg Betaseron, 250 mcg Betaseron, or placebo was administered subcutaneously
every other day |
20
mg glatiramer acetate or placebo administered subcutaneously once a day |
44
mcg, 22 mcg, or placebo administered subcutaneouously three times per week |
| Length
of Study |
Up
to 2 years* |
Up
to 2 years |
Up
to 2 years |
Up
to 2-years |
| Primary
Outcome |
Time
to progression of physical disability |
Frequency
of exacerbations and the proportion of patients that remained exacerbation-free |
Proportion
of patients that remained exacerbation-free and the frequency of exacerbations |
Number
of relapses over the 2 year study period |
| Results |
Avonex |
Betaseron |
Copaxone |
Rebif |
| Decrease
in relapse rate |
The
intent to treat analysis revealed an 18%** reduction in annual exacerbation
rate in patients receiving Avonex (p=0.04) |
A
31% reduction in annual exacerbation rate was associated with active treatment |
There
was a 29% reduction in relapse rate |
A
33% reduction in relapse rate was noted among patients receiving Rebif
44 mcg subcutaneouously 3 times per week and 27% in the 22 mcg treatment
group, compared with placebo |
Proportion
of patients exacerbation-free
|
38%
of patients who received Avonex remained free of exacerbation, compared
with 26% who received placebo |
The
proportion of patients that were exacerbation-free was 16% in the placebo
group compared with 25% in the 250 mcg Betaseron group |
No
significant difference was found, though a trend favoring Copaxone was
noted |
32%
of patients in the Rebif 44 mcg treatment group and 27% of patients in
the Rebif 22 mcg treatment group remained exacerbation-free over 2 years,
compared with 16% in the placebo group (P<0.005 and P<0.05,
respectively) |
| Time
to first exacerbation |
Not
measured in this trial |
The
time to first exacerbation was 9 months compared with 5 months in the placebo
group |
No
significant difference was found, though a trend favoring Copaxone was
noted |
The
time to first exacerabation was delayed by a median of 3 and 5 months in
the Rebif 22 mcg and Rebif 44 mcg treatment groups, respectively |
| Disease
progression as measured by physical disability |
Patients
treated with Avonex had a 37% reduced risk of accumulating disability |
No
significant difference in disability by the end of the 2-year study period
in this trial |
Although
some patients receiving Copaxone reported improvement in disability, there
was no difference in the proportion of progression-free patients after
2 years |
Time
to progression was significantly longer in both active treatment groups
than in the placebo group (P<0.05) |
| |
Avonex |
Betaseron |
Copaxone |
Rebif |
| Disease
progression as measured by MRI |
Avonex-treated
patients had fewer number of lesions and less lesion volume |
Betaseron
was associated with a reduction in the burden and the progression of disease
as evidenced by MRI |
Only
a small number of patients were included in the MRI evaluation. Although
there was a decrease in the number and volume of lesions, the difference
was not considered significant |
Significant
reductions in the burden of disease were found in both Rebif active treatment
groups, compared with placebo-treated patients (P<0.0001), and
a dose-effect was noted |
| Other |
It
is important to note that other trials in which higher doses of interferon
beta-1a have been used show better effect of the drug. However, the only
dose of interferon beta-1a approved in the US is the one used in the study
described above |
There
was a 51% decrease in number of moderate or severe exacerbations |
|
No
significant difference in the incidence of depression was reported in this
trial |
Comparative Trials
The only published study comparing 2 different
active drugs against one another is described below
|
| Number
of Patients Enrolled |
188
patients |
| Dosing
Regimen Used |
Avonex
30 mcg intramuscularly once a week or Betaseron 8 million IU (0.25 mg)
subcutaneously every other day |
| Length
of Study |
1
year |
Results
|
| Decrease
in relapse rate |
Betaseron
was associated with a 46% risk reduction compared to Avonex after one year
of treatment. |
| Proportion
of patients exacerbation-free |
At
1 year, the proportion of patients exacerbation-free was 80% in the Avonex
group compared with 89% in the Betaseron group |
| Time
to first exacerbation |
Not
measured in this trial |
| Disease
progression as measured by physical disability |
Patients
treated with Betaseron had a 72% reduced risk of accumulating disability
compared with patients receiving Avonex |
| Disease
progression as measured by MRI |
Betaseron
reduced signs of disease activity better than Avonex after 1 year of treatment |
*57% of the total number of patients enrolled (n=301) were followed
for a full two-year period because trial enrollment ended early.
**The reduction in relapse rate among all patients enrolled in the study
(n=301) was 18%. A 32% reduction in the number of exacerbations was reported
for the subset of 172 patients who completed a 2 year follow-up.
***PRISMS Study Group. Randomized double-blind placebo-controlled study
of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet
1998;352:1498-1504