Betaseron (interferon beta-1b) for multiple sclerosis

 

What is Betaseron for MS?

An approved injectable therapy, Betaseron (interferon beta-1b) can help reduce the frequency of disease relapses and prevent the development of new brain lesions on MRI scans in people with relapsing forms of multiple sclerosis (MS).

The therapy was originally developed by Chiron, but was licensed to Bayer in 1993. Chiron was later acquired by Novartis. Under an agreement between the companies, Bayer gained full rights to Betaseron, while Novartis developed its own interferon beta-1b product, Extavia.

Betaseron was the first disease-modifying therapy to be approved in the U.S. for relapsing MS.

Therapy Snapshot

Brand name:	Betaseron
Chemical name:	Interferon beta-1b
Usage:	Disease-modifying therapy for relapsing forms of MS
Administration:	Subcutaneous injection

 

How does Betaseron work?

In MS, the body’s immune system erroneously launches an inflammatory attack that damages healthy parts of the nervous system. The active agent in Betaseron, interferon beta-1b, is a naturally occurring signaling protein produced by immune cells to communicate with each other, namely to dampen inflammatory immune responses.

Although the exact details of its mechanism of action are unclear, Betaseron is thought to shift the immune system toward an anti-inflammatory response and to reduce the number of immune cells capable of reaching the brain and spinal cord. That helps to lessen nervous system damage in MS.

Who can take Betaseron?

The U.S. Food and Drug Administration approved Betaseron in 1993, making it the first disease-modifying therapy for relapsing-remitting MS (RRMS). That approval was later expanded in 2006 to include clinically isolated syndrome (CIS), and in 2019 to cover active secondary progressive MS (SPMS).

Betaseron is approved in more than 100 countries for the same indications. It is available in Canada, Australia, New Zealand, and South Africa, as well as in a number of Asian and Latin American countries. Outside North America, the therapy is marketed under the brand name Betaferon.

In the European Union, Betaferon was first approved in 1995 for RRMS, an approval later expanded to include CIS and active SPMS patients.

Who should not take Betaseron?

The treatment is not recommended for use in people with a known allergy to interferon beta products, or to the inactive ingredients in Betaseron, specifically albumin and mannitol.

How is Betaseron administered?

Betaseron is given via a subcutaneous, or under the skin, injection. It is available as a dry powder that must be diluted in an appropriate liquid solution contained in a prefilled syringe.

After injecting the solution of the prefilled syringe into the Betaseron vial, the vial must be gently swirled, not shaken. If not used immediately, the reconstituted medication should be refrigerated and used within three hours. The vials should not be frozen.

The recommended dose is 0.25 mg, or 1 mL of the resuspended treatment, given every other day. However, patients starting on the medication must gradually increase their dosage over the course of six weeks. This dosing or titration scheme involves:

• a 0.0625 mg dose, or 0.25 mL, over weeks 1 and 2
• a 0.125 mg dose, or 0.5 mL, over weeks 3 and 4
• a 0.1875 mg dose, or 0.75 mL, over weeks 5 and 6

Betaseron is administered via the BetaConnect autoinjector, and each injection takes about 17 to 23 seconds. The therapy may be self-administered or otherwise given at home, but patients and caregivers need prior training and supervision from a qualified healthcare provider.

The medication should preferably be given in loose and soft skin, such as the stomach region, the thigh or buttocks, or the upper arms. Areas such as joints, nerves, and bones, and those near the belly button or waist, should be avoided. Thinner patients should receive the injection only in the thigh or on the outer surface of the arm.

The sites of injection should be rotated to avoid injection site reactions including infection or tissue death (necrosis). Taking over-the-counter pain medicines (analgesics) or anti-fever medications on treatment days may help reduce the severity of flu-like symptoms, which also are common in people receiving Betaseron.

The autoinjection can be linked to a smartphone app called myBETAapp. This app helps patients track their injection history and displays the date and location of the next scheduled injection. It also has the option of sharing information with healthcare professionals.

Administration	Subcutaneous injection in stomach region, the thigh or buttocks, or the upper arms
Dosage	0.25 mg, or 1 mL of resuspended treatment (during titration period, dose of 0.0625 mg, or 0.25 mL, over weeks 1 and 2; 0.125 mg, or 0.5 mL, over weeks 3 and 4; and 0.1875 mg dose, or 0.75 mL, over weeks 5 and 6
Timing	Every other day

 

Betaseron in clinical trials

The approvals of Betaseron were based on data from four clinical trials — one in RRMS, two in SPMS, and one in CIS. Altogether, the trials tested the medication against a placebo in a combined total of about 2,500 patients.

RRMS trial

The first clinical trial enrolled 372 adults with RRMS and randomly assigned them to receive one of two doses of Betaseron (0.25 or 0.05 mg), or a placebo. Treatment was given subcutaneously every other day for three years.

Results showed that the 0.25 mg dose significantly reduced the average annual relapse rate compared with a placebo (0.9 vs. 1.31 relapses per year, per the medication’s label) over two years. The mean area of brain lesions also was reduced by 0.9% after two years on the high-dose treatment. That compared with a 21.4% increase among patients given a placebo. The treatment also significantly reduced the severity of disease relapses, the number of days of steroid use, and MS-related hospitalizations.

SPMS trials

Betaseron was investigated in SPMS patients with active disease in two clinical trials. One involved 718 patients in Europe and another enrolled 939 individuals with SPMS in the U.S.

Both tested the 0.25 mg dose of Betaseron against a placebo, although the U.S.-based trial included another group of patients who received a dose of 0.16 mg per square meter (m²) of body surface area. Participants received their assigned treatment every other day for three years.

A significant reduction in relapse rates and in brain lesions was demonstrated among people receiving Betaseron in both studies. In the European study, the mean annual relapse rates were 0.44 in treated patients and 0.64 for the placebo group, representing a 30% reduction. The volume of brain lesions also dropped by 5% among patients receiving Betaseron, compared with an 8% increase in the placebo group.

In the U.S. study, the mean annual relapse rates were 0.16 and 0.20 (among patients treated with Betaseron at 0.25 mg or 0.16 mg/m², respectively), and 0.28 for those on a placebo. Overall, Betaseron treatment reduced relapse rates by 36%, and reduced the total number of lesions with active inflammation by 71%, compared with a placebo.

However, only the European study met the primary goal of delaying confirmed disability progression, defined as an increase on Expanded Disability Status Scale (EDSS) scores that was sustained for at least six months. In this trial, about half of patients on a placebo (49.7%) experienced such progression of disability, compared with 38.9% of those receiving Betaseron.

BENEFIT trial

A Phase 3 trial called BENEFIT (NCT00185211) then investigated Betaseron in people with CIS. All of the participants had experienced their first episode of MS-like symptoms in the prior 60 days. A total of 468 individuals were enrolled and treated with 0.25 mg Betaseron or a placebo for two years.

In this trial, Betaseron significantly reduced the likelihood of progressing to clinically definite MS by 50% over the two years. About 44% of patients on a placebo progressed, compared with 26% of those on the active treatment group. Patients on Betaseron also had fewer brain lesions, and a lower volume of lesions with active inflammation.

Just over half of the patients in BENEFIT then enrolled in an open-label extension part, in which all continued to receive treatment with Betaseron. After more than a decade of follow-up, participants originally assigned to Betaseron continued to have a lower risk of transitioning to clinically definite MS than those originally given a placebo. The fully Betaseron-treated patients also had significantly lower rates of relapses (0.21 vs. 0.26 relapses per year).

Common side effects of Betaseron

For the patients in the Betaseron clinical trials, the most common side effects of the medication included:

• injection site reactions
• flu-like symptoms
• low blood cell counts, particularly of lymphocytes and neutrophils
• headache
• rash
• insomnia
• muscle pain and increased muscle tone
• abdominal pain
• lack of energy
• elevated levels of liver enzymes
• pain

Injection site reactions

Injection site reactions are common in people receiving Betaseron or other interferon-based medications. Symptoms normally include pain, inflammation, a mass, or swelling, but some reactions may lead to the death of nearby tissue (necrosis).

Decreased blood cell counts

Betaseron may cause a reduction in the levels of certain white blood cells called leukocytes, which may require a dose reduction in some patients. Patients should be regularly monitored for complete blood counts while on this therapy.

Liver injury

Betaseron can cause liver problems, leading to liver failure in rare cases. The medication should be used with caution in people who regularly drink alcohol or are taking other therapies that can also damage the liver. Liver health should be monitored while taking the medication, and discontinuation may be considered in patients showing signs or symptoms of liver damage.

Heart problems

Some patients on Betaseron developed heart failure and other conditions affecting the heart muscle. Patients with a history of heart failure should be monitored for worsening cardiac symptoms, and the therapy should be stopped if such worsening occurs without any other explanation.

Psychological issues

Betaseron carries a warning for mental health problems including depression and suicidal ideation, which includes thinking about suicide. Such issues should be immediately discussed with a healthcare professional. In patients who develop depression, treatment discontinuation should be considered.

Allergic reactions

Some people may experience an allergic reaction to Betaseron; the medication should not be used in people with a known allergy to any of its components and it should be discontinued if an allergic reaction occurs.

Blood vessel damage

Cases of thrombotic microangiopathy, a condition in which blood clots cause damage to the body’s small blood vessels, have been reported in patients on Betaseron. The treatment should be discontinued if signs of this disease occur.

Drug-induced autoimmune diseases

Some cases of drug-induced lupus erythematosus — a lupus-like condition caused by certain prescription therapies — also were observed. Betaseron should be stopped in anyone experiencing symptoms suggestive of this disease.

Use in pregnancy and breastfeeding

Data from animal studies suggest that Betaseron may harm a developing fetus. Well-controlled trials of Betaseron use during pregnancy are lacking, but available data — which includes prospective observational studies — indicate that the medication is not generally associated with a risk of major birth defects.

It is unknown if Betaseron can pass to breast milk. Patients who plan to become pregnant or to breastfeed should talk with their healthcare professionals. Treatment should only be continued during these periods if the potential benefit justifies the potential risks to the fetus or child.

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Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.