Indications for: AVONEX
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
The efficacy of Avonex was based on data from 2 randomized, multicenter, double-blind, placebo-controlled studies (Studies 1 and 2) in patients with relapsing forms of MS.
The study included 301 patients who had a definite diagnosis of multiple sclerosis of at least 1 year duration and had at least 2 exacerbations in the 3 years prior to study entry. At entry, study participants were without exacerbation during the prior 2 months and had Kurtzke Expanded Disability Status Scale (EDSS3 ) scores ranging from 1.0 to 3.5.
Patients received either Avonex 30mcg (n=158) or placebo (n=143) intramuscularly once weekly for up to 2 years, and continued to be followed until study completion. The primary outcome measure was time to progression in disability, measured as an increase in the EDSS score of at least 1 point that was sustained for at least 6 months.
Results showed that the time to onset of sustained progression in disability was significantly longer in Avonex-treated patients at the end of 2 years vs placebo-treated patients (22% vs 35%, respectively; P =.02); this correlated to a 37% relative reduction in the risk of accumulating disability in the Avonex treatment arm.
A statistically significant difference was observed between the Avonex and placebo arms in confirmed change for patients with at least 2 scheduled visits (0.20 vs 0.50, respectively; P =.006).
For all patients included in the study, the annual exacerbation rate was 0.67 per year in the Avonex-treated arm and 0.82 per year in the placebo-treated arm (P =.04).
For the subset of patients who were enrolled in the study for at least 2 years, the frequency of exacerbations was significantly decreased in patients treated with Avonex (P =.03).
MRI Results: Treatment with Avonex had significantly lower Gd-enhanced lesion number after 1 and 2 years vs placebo (P ≤.05). The volume of Gd-enhanced lesions showed similar treatment effects in the Avonex and placebo arms (P ≤.03). Percentage change in T2-weighted lesion volume from study entry to Year 1 was significantly lower in Avonex-treated than placebo-treated patients (P =.02).
The study included 383 patients who had recently experienced an isolated demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and who had lesions typical of multiple sclerosis on brain MRI.
Patients received either Avonex 30mcg (n=193) or placebo (n=190) intramuscularly once weekly for up to 2 years, and followed for up to 3 years or until they developed a second clinical exacerbation in an anatomically distinct region of the central nervous system. The primary outcome measure was time to development of a second exacerbation in an anatomically distinct region of the central nervous system.
Results showed that the time to development of a second exacerbation was significantly delayed in Avonex-treated vs placebo-treated patients (21% vs 39%, respectively; P =.002). The relative rate of developing a second exacerbation in the Avonex group was 0.56 of the rate in the placebo group (95% CI, 0.38-0.81).
MRI Results: Patients treated with Avonex achieved a lower actual and percentage change from baseline in T2 volume of lesions at 18 months vs those treated with placebo (both P <.001). Treatment with Avonex had a significantly lower number of Gd-enhancing lesions at 6 months vs placebo (P <.03). Avonex also had fewer new or enlarging T2 lesions at 18 months vs placebo (P <.001).
Pre-medicate with analgesics and/or antipyretics on treatment days to ameliorate flu-like symptoms. Rotate inj sites. ≥18yrs: 30mcg IM once weekly. May titrate dose to reduce severity of flu-like symptoms; dosed once weekly, IM: Week 1: 7.5mcg. Week 2: 15mcg. Week 3: 22.5mcg. Week 4: 30mcg.
<18yrs: not established.
Depression, Suicide, and Psychotic Disorders
Immediately report any symptoms of depression, suicidal ideation, and/or psychosis to physicians. Consider discontinuing therapy if depression or other severe psychiatric symptoms develop.
Severe hepatic injury, including cases of hepatic failure, has been reported rarely.
Consider the potential risk of Avonex in combination with known hepatotoxic drugs or other products (eg, alcohol) before starting Avonex or other hepatotoxic drugs. Monitor for signs of hepatic injury.
Anaphylaxis and Other Allergic-Reactions
Discontinue if anaphylaxis or other allergic reactions (eg, dyspnea, orolingual edema, skin rash, urticaria).
Injection Site Reactions Including Necrosis
Injection site reactions (eg, abscesses, cellulitis, necrosis) may occur.
Evaluate periodically and use aseptic self-injection techniques and procedures.
For patients who continue therapy with Avonex after injection site necrosis has occurred, avoid administration into the affected area until it is fully healed.
If multiple lesions occur, change injection site or discontinue therapy until healing occurs.
Congestive Heart Failure
For patients with pre-existing CHF, monitor for worsening cardiac condition during initiation and during treatment.
Decreased Peripheral Blood Counts
Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported.
Monitor for signs or symptoms of decreased blood counts.
Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported.
Discontinue if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
It is not known whether these events were related to the effects of multiple sclerosis alone, to Avonex, or to a combination of both.
Consider discontinuing treatment if new autoimmune disorder occurs.
Monitor CBCs, differential, platelets, blood chemistries, liver and thyroid function during treatment.
Depression. Suicidal ideation. Pre-existing psychiatric disorders (eg, psychosis). Seizure disorders. Monitor for hepatic injury. Pre-existing CHF: monitor for worsening cardiac function at initiation and during treatment. Risk of thrombotic microangiopathy; discontinue if occurs. Myelosuppression. Monitor CBCs, differential, platelets, blood chemistries, liver and thyroid function. Consider discontinuing if new autoimmune disorder develops. Periodically evaluate patients for aseptic self-injection techniques. Latex allergy. Pregnancy. Nursing mothers.
Risk of hepatic injury with concomitant hepatotoxic drugs or alcohol.
Flu-like symptoms, asthenia, headache, myalgia, fever, chills, GI upset, depression, blood dyscrasias, seizures, inj site reactions (necrosis, cellulitis, abscess, inflammation, pain); rare: hepatic injury, anaphylaxis (discontinue if occurs).
Register pregnant patients exposed to Avonex by calling (800) 456-2255.
Half-life: 19 hours.
Generic Drug Availability:
Single-use prefilled syringe, autoinjector (Avonex Pen)—1, 4 (w. supplies)