Indications for: BETASERON
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Patients with Relapsing-Remitting Multiple Sclerosis
- Study 1: Double-blind, multiclinic, randomized, parallel, placebo-controlled clinical study of 2 years duration.
- Study included patients aged 18 to 50 years who were ambulatory, exhibited a relapsing-remitting clinical course, met Poser’s criteria for clinically definite and/or laboratory supported definite MS and had experienced at least 2 exacerbations over 2 years preceding the trial without exacerbation in the preceding month.
- Patients were randomly assigned to Betaseron 0.05mg, Betaseron 0.25mg, or placebo administered subcutaneously every other day.
- Primary outcomes: 1) frequency of exacerbations per patient and 2) proportion of exacerbation free patients.
- Annual exacerbation rate: 1.14, 0.9 and 1.31 for Betaseron 0.05mg, 0.25mg, and placebo, respectively.
- Proportion of exacerbation-free patients: 18%, 25%, and 16% for Betaseron 0.05mg, 0.25mg, and placebo, respectively.
- The average number of days of MS-related steroid use was 41 days in the 0.25mg Betaseron group and 55 days in the placebo group (P =.004).
- In an evaluation of frequent MRI scans (every 6 weeks) on 52 patients at 1 site, the percent of scans with new or expanding lesions was 29% in the placebo group and 6% in the 0.25mg treatment group (P =.006).
Patients with Secondary Progressive Multiple Sclerosis
- Two randomized, double-blind, placebo-controlled trials conducted to assess the effect of Betaseron in patients with secondary progressive MS.
- Study 2: Patients randomly assigned to Betaseron 0.25mg (n=360) or placebo (n=358).
- Study 3: Patients randomly assigned to Betaseron 0.25mg (n=317), Betaseron 0.16mg/m2 of body surface area (n=314) or placebo (n=308).
- Primary outcome: Progression of disability, defined as a 1.0 point increase in the EDSS score, or a 0.5 point increase for patients with baseline EDSS ≥ 6.0.
- Study 2: Time to progression in EDSS was longer in the Betaseron treatment group (P =.005), with estimated annualized rates of progression of 16% and 19% in the Betaseron and placebo groups, respectively. The mean annual relapse rates were 0.42 and 0.63 in the Betaseron and placebo groups, respectively (P <.001).
- Study 3: Rates of progression did not differ significantly between treatment groups, with estimated annualized rates of progression of 12%, 14%, and 12% in the Betaseron fixed dose, surface area-adjusted dose, and placebo groups, respectively. The mean annual relapse rates were 0.16, 0.20, and 0.28, for the fixed dose, surface area-adjusted dose, and placebo groups, respectively (P <.02).
- Smaller increases in T2 MRI lesion area and decreased number of active MRI lesions were observed in patients in the Betaseron groups vs the placebo group.
Patients with an Isolated Demyelinating Event and Typical MS Lesions on Brain MRI
- Study 4: 468 patients who had recently (within 60 days) experienced an isolated demyelinating event, and who had lesions typical of MS on brain MRI were randomized to receive either Betaseron 0.25mg (n=292) or placebo (n=176) subcutaneously every other day (ratio 5:3).
- Primary outcome: Time to development of a second exacerbation with involvement of at least 2 distinct anatomical regions.
- Time to development of a second exacerbation was significantly delayed in patients treated with Betaseron compared with patients treated with placebo (P <.0001).
- Kaplan-Meier estimates of the percentage of patients developing an exacerbation within 24 months were 45% in the placebo group and 28% of the Betaseron group.
- Risk for developing a second exacerbation in the Betaseron group was 53% of the risk in the placebo group (hazard ratio, 0.53; 95% CI, 0.39-0.73).
- Patients treated with Betaseron demonstrated a lower number of newly active lesions during the course of the study. A significant difference between Betaseron and placebo was not seen in the absolute change in T2 lesion volume during the course of the study.
Pre-medicate with analgesics and/or antipyretics on treatment days to ameliorate flu-like symptoms. May be administered by syringe and needle or Betaconnect autoinjector. Rotate inj sites. ≥18yrs: initially 0.0625mg (0.25mL) SC every other day; increase by 25% every 2 weeks to target dose of 0.25mg (1mL) SC every other day.
<18yrs: not established.
Monitor for hepatic injury; consider discontinuing if elevated transaminase levels or jaundice occurs. Depression. Suicidal ideation. Pre-existing CHF: monitor for worsening cardiac function at initiation and during treatment. Discontinue if thrombotic microangiopathy or signs/symptoms of drug-induced lupus erythematosus occurs. Myelosuppression. Monitor CBCs, differential, platelets, blood chemistries; liver function tests (at 1, 3, and 6 months then periodically). Pregnancy. Nursing mothers.
Risk of hepatic injury with concomitant hepatotoxic drugs or alcohol.
Inj site reactions (necrosis, cellulitis, abscess, inflammation, pain), lymphopenia, flu-like symptoms, myalgia, leukopenia, neutropenia, increased liver enzymes, headache, hypertonia, pain, rash, insomnia, abdominal pain, asthenia; rare: hepatic injury, anaphylaxis (discontinue if occurs), possible seizures.
Half-life: 8 minutes–4.3 hours.
Generic Drug Availability:
Single-use vials (w. prefilled diluent syringe, supplies)—5, 14