|Clinical Trials||Disease progression as measured by physical disability||Indications||Primary Outcome|
|Common Adverse Reactions||Dosage/ Administration||Length of Study||Proportion of patients exacerbation-free|
|Comparative Trials||Dosing Regimen Used||Manufacturer||Shelf Life|
|Contraindications||Drug Interactions||Number of Patients Enrolled||Storage|
|Decrease in relapse rate||Generic Name||Nurse Counseling||Time to first exacerbation|
|Disease progression as measured by MRI||How Supplied||Precautions||Warnings|
|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.
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.
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|
|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|
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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:
|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|
|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|
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)|
|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|
|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|
|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
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