Betaseron® (interferon beta-1b)
FDA-Approved Medications: Administered by Self-Injection
Company: Bayer HealthCare Pharmaceuticals
- Administered by subcutaneous injection every other day; dose is 250 mcg
- Approved for relapsing forms of MS in 1993, and more recently, for individuals with CIS
Betaseron reduces the number and severity of relapses (attacks) of MS. It also stabilizes the total lesion area as measured by MRI, compared to those without treatment.
Interferons appear to reduce inflammation by modulating a favorable balance between cells that increase inflammation and decrease inflammation. They also reduce the transport of damaging lymphocytes into the brain.
Follow-up data after 21 years from Betaseron’s initial Phase III trial of RRMS1 show continued effectiveness and safety, as well as increased longevity. Following 21 years after the enrollment of this pivotal trial, Goodin and colleagues examined the effect of randomization to Betaseron versus placebo in the group of 372 patients on mortality. They found that patients originally assigned randomly to Betaseron showed a 50-percent reduction in mortality over the 21-year period compared with placebo.
The researchers conclude that the study provides evidence that early treatment with Betaseron (versus no treatment or delayed treatment) is associated with longer survival in people with relapsing-remitting MS (RRMS). The results suggest that treatment was more effective when given early in the course of the disease, and a more favorable outcome can be seen for those patients who received the active drug in the very first trials when evaluated two decades later.
Improved effects of early treatment were also demonstrated in a group of 468 patients with CIS who were randomized to active treatment or placebo in the BENEFIT trial. In this trial, patients were treated with Betaseron or placebo for up to two years after a CIS event. After two years, all patients enrolling in the extension trial were treated with Betaseron moving forward. In this way, there was an “early-treatment group” and a “delayed-treatment group.” In addition to the effect on reducing the risk of MS relapses and MRI lesions, by five years, the treated group showed greater improvement in scores on the Paced Auditory Serial Addition Test (PASAT), a measure of cognitive function. A follow-up BENEFIT trial extension study at eight years presented in 2013 showed both groups had stable or low disability levels, although the patients treated immediately with Betaseron following CIS had fewer relapses than those with delayed treatment.
The small START study of patients with RRMS was designed to identify immune markers of Betaseron therapy. Immune markers are tendencies or indicators observed across a population with a particular disease state. Immune markers in this study were compared in those patients with and without relapses during the first year of treatment.
The study revealed that the patients treated with Betaseron had significant changes in the levels of several immune-system markers. A trend toward higher levels of the pro-inflammatory cytokine interleukin-17 (IL-17) was found in patients who relapsed. (Cytokines are small proteins that may stimulate or inhibit the function of other cells, and can be studied in the blood.) Higher brain-derived neurotrophic factor (BDNF) levels were observed in the relapse-free group. (BDNF is a protein found in the brain that helps to support nerves and their development.)
The data suggest that the mode of action of the beta interferons may involve a shift in cytokines in favor of an anti-inflammatory/ regulatory profile. Findings also suggest that elevated IL-17 may correlate with having relapses, while increased levels of another cytokine, BDNF, may be protective. These findings serve as a platform for further research of biomarkers predictive of responses to interferon therapy. More discussion on the potential role of biomarkers in the future of MS therapy is given later in this publication.