FDA Approvals: Interferon-beta-1b (Betaseron) for Use in Early Multiple Sclerosis


On October 10, the FDA approved an expanded indication for interferon-beta-1b subcutaneous injection (Betaseron, made by Berlex, Inc [a US affiliate of Schering AG]), allowing its use in patients with multiple sclerosis (MS) who have experienced a first clinical episode and have magnetic resonance imaging features consistent with the disease. Interferon-beta-1b previously was approved to reduce the frequency of clinical exacerbations in patients with relapsing forms of MS.

Expansion of the indication was based on data from the BEtaseron in Newly Emerging multiple sclerosis for Initial Treatment (BENEFIT) study of 468 patients with a first demyelinating event and magnetic resonance imaging features suggestive of MS. Enrollees were randomized to receive subcutaneous injections of either placebo or 250 µg of interferon-beta-1b every other day until they experienced a second clinical event or had been followed up for 24 months. Doses were titrated slowly, and injections were preceded by use of analgesics.

Results showed that time to development of a second exacerbation were significantly delayed in patients receiving treatment with interferon-beta-1b vs placebo (P < .0001). Kaplan-Meier estimates suggested that 28% vs 45% of patients developed an exacerbation within the 2-year period (hazard ratio, 0.53; 95% confidence interval, 0.39 - 0.73). Interferon-treated patients also demonstrated a lower number of newly active lesions during the course of the study; however, no significant differences were observed between groups in terms of absolute changes of lesion volume.

According to a company news release, the trial is the first to demonstrate the efficacy of a high-dose, high-frequency interferon-beta as an effective treatment of patients with early MS. It also showed that most patients were willing to initiate and continue treatment (93% completion rate; 96% opted to enroll in a 3-year extension study). Also, the discontinuation rate due to adverse events was low (2.7%). Lymphopenia, injection-site reaction, asthenia, flu-like symptom complex, headache, and pain were most commonly reported. Anaphylaxis has been reported rarely.

The recommended starting dose for interferon-beta-1b is 0.0625 mg (0.25 mL) injected subcutaneously every other day and then titrated upwards during a 6-week period to 0.25 mg (1.0 mL) every other day. Gradual dose titration and the use of analgesics during initial therapy may help to reduce flu-like symptoms. Patients should be advised of the need for rotating injection sites to minimize the risk for severe injection site reactions, including necrosis or localized infection.