Indications
BETASERON® (interferon beta-1b) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Have you explored the pregnancy data from 2 observational studies in patients treated with BETASERON®?
Women of childbearing age make up a considerable percentage of all MS patients, with approximately 10% experiencing disease onset during pregnancy.1
The effects of exposure to disease-modifying treatments can be a major concern during pregnancy. Data are limited.2
Over several years, the US BETASERON Pregnancy Registry and the European IFN-beta Pregnancy Registry have collected information on the rates of pregnancy and infant outcomes in women receiving BETASERON.
An excerpt from the BETASERON US Prescribing Information (USPI)
Pregnancy
Risk Summary
Although there have been no well-controlled studies in pregnant women, available data—which include prospective observational studies—have not generally indicated a drug-associated risk of major birth defects with interferon beta-1b use during pregnancy. Administration of BETASERON to monkeys during gestation resulted in increased embryo-fetal death at or above exposures greater than 3 times the human therapeutic dose.3
In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.3
Human Data
The majority of observational studies reporting on pregnancies exposed to interferon beta-1b did not identify an association between the use of interferon beta-1b during pregnancy and an increased risk of major birth defects.3
Breastfeeding
Risk Summary
There are no data on the presence of BETASERON in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.3
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BETASERON and any potential adverse effects on the breastfed child from BETASERON or from the underlying maternal condition.3
Rates of birth defects and spontaneous abortions from the US BETASERON Pregnancy Registry
Study Overview
- Observational study to estimate the rates of birth defects, spontaneous abortions, and other negative outcomes in US women exposed to BETASERON during pregnancy from 2006 to 20112
- Almost 100 BETASERON pregnancy outcomes were evaluated in the US BETASERON Pregnancy Registry2
Study Results
- A total of 99 birth outcomes were available from 96 evaluable pregnancies2
- Initial exposure to BETASERON occurred in the first trimester for 95 patients, and in the third trimester for one patient2
- Rates of birth defects and spontaneous abortions were not significantly different from population comparators2
Pregnancy outcomes in the US BETASERON Pregnancy Registry2
*Excludes spontaneous and elective abortions <20 weeks gestation with reported birth defects per MACDP convention. The denominator is restricted to live births.2
†Relative risk compared with 2.78% reported by MACDP.2
‡Relative risk compared with 16% rate of spontaneous abortion reported by National Survey of Family Growth.2
Limitations
- The exclusion of retrospective patients could have introduced the potential for under-reporting or differential reporting2
- Birth defects were reported voluntarily, which could limit the level of detail provided2
- Data on infant outcomes were only collected for 4 months after birth, reducing the ability to measure infants’ developmental progress2
- The relatively small sample size limits the ability to draw definitive conclusions2
- Observational studies are a lower standard of evidence than experimental studies; are more prone to bias and confounding; and cannot be used to demonstrate causality4
Pregnancy outcomes from the European IFN-beta Pregnancy Registry
Study Overview
- Observational study to estimate the prevalence of pregnancy and infant outcomes in pregnant women from 26 countries of the European Economic Area exposed to interferon beta-1a or interferon beta-1b from 2009 to 20175
- More than 2000 pregnancy reports were collected and more than 900 known outcomes were evaluated5
Study Results
- The majority of pregnancies were last exposed to interferon beta before conception (13.0%; 90/694) or during the first trimester (82.6%; 573/694). The mean duration of exposure during pregnancy was 4.31 weeks, with a standard deviation of 5.445
- A total of 948 pregnancy outcomes were available from the 2447 pregnancies reported5
- The prevalence of spontaneous abortions and congenital anomalies in live births was found to be within the ranges reported in the general population5
Pregnancy outcomes from the European IFN-beta Pregnancy Registry5
§Spontaneous abortion was defined as the pregnancy spontaneously ending before 22 completed weeks of gestation (<24 weeks from last menstrual period) and comprising spontaneous abortion, miscarriage, missed abortion, incomplete abortion, and early fetal death.5
Limitations
- This analysis did not separate pregnancy outcomes for different interferon beta products (eg, interferon beta-1a or interferon beta-1b), limiting the potential to identify unique trends associated with specific interferon beta treatment types5
- Only pregnancies with known outcomes were included in the final analysis, which could lead to selection bias towards the presence of adverse pregnancy outcomes or towards women with higher healthcare-seeking behavior5
- This study did not control for possible confounding factors, such as family history, medical history, interferon beta dose and duration of exposure, comorbidities, or exposure to comedications, nor did the study collect any substantial data on birth weight, birth length, or gestational age at birth to allow for a comprehensive analysis5
- Observational studies are a lower standard of evidence than experimental studies, are more prone to bias and confounding, and cannot be used to demonstrate causality4
CI, confidence interval; IFN-beta, interferon-beta; MACDP, Metropolitan Atlanta Congenital Defects Program; MS, multiple sclerosis; N/A, not available.
References:1. Bennett KA. Pregnancy and multiple sclerosis. Clin Obstet Gynecol. 2005;48(1):38-47. doi:10.1097/01.grf.0000153881.20014.86 2.Coyle PK, Sinclair SM, Scheuerle AE, Thorp Jr JM, Albano JD, Rametta MJ. Final results from the Betaseron (Interferon β-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events. BMJ Open. 2014;4(5):e004536. doi:10.1136/bmjopen-2013-004536 3.BETASERON. Prescribing Information. Bayer HealthCare Pharmaceuticals Inc.; 2023. 4. Reeves BC, Deeks JJ, Higgins JPT, Shea B, Tugwell P, Wells GA. Chapter 24: Including non-randomized studies on intervention effects. In: Higgins, J, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, eds. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane; 2023. 5. Hellwig K, Geissbuehler Y, Sabidó M, et al; European Interferon-beta Pregnancy Study Group. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry. J Neurol. 2020;267(6):1715-1723. doi:10.1007/s00415-020-09762-y
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INDICATIONS
BETASERON® (interferon beta-1b) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
IMPORTANT SAFETY INFORMATION
Do not take BETASERON (interferon beta-1b) if you are allergic to interferon beta-1b, to another interferon beta, to human albumin, or mannitol.
BETASERON can cause serious side effects, including:
Liver Problems Including Liver Failure. Symptoms of liver problems may include yellowing of your eyes, itchy skin, feeling very tired, flu-like symptoms, nausea or vomiting, bruising easily or bleeding problems. Your healthcare provider will do blood tests to check for these problems while you take BETASERON.
Serious Allergic Reactions. Serious allergic reactions can happen quickly and may happen after your first dose of BETASERON or after you have taken BETASERON many times. Symptoms may include difficulty breathing or swallowing, swelling of the mouth or tongue, rash, itching, or skin bumps.
Depression or Suicidal Thoughts. Call your healthcare provider right away if you have any of the following symptoms, especially if they are new, worse or worry you: thoughts about suicide or dying, new or worse depression (sinking feeling or sadness), new or worse anxiety (feeling uneasy, nervous or fearful for no reason), trouble sleeping (insomnia), acting aggressive, being angry, or violent, acting on dangerous impulses, hallucinations, other unusual changes in behavior or mood.
Other possible serious side effects with BETASERON include:
Heart Problems. BETASERON may worsen heart problems including congestive heart failure. Symptoms of heart problems may include swollen ankles, shortness of breath, decreased ability to exercise, fast heartbeat, tightness in chest, increased need to urinate at night, not being able to lay flat in bed.
Injection Site Problems. Serious skin reactions can happen in some people including areas of severe damage to skin and the tissue below the skin (necrosis). These reactions can happen anywhere you inject BETASERON. Symptoms of injection site problems may include swelling, redness, or pain at the injection site, fluid drainage from the injection site, and breaks in your skin or blue-black skin discoloration. Call your healthcare provider right away if an injection site becomes swollen and painful or the area looks infected. You may have a skin infection or an area of severe skin damage (necrosis) requiring treatment by a healthcare provider.
Pulmonary Arterial Hypertension. Pulmonary arterial hypertension can occur with interferon beta products, including BETASERON. Symptoms may include new or increasing fatigue or shortness of breath. Contact your healthcare provider right away if you develop these symptoms.
Flu-like Symptoms. BETASERON can cause flu-like symptoms including fever, chills, tiredness, sweating, muscle aches when you first start to use it. These symptoms may decrease over time. Taking medicines for fever and pain relief on the days you are using BETASERON may help decrease these symptoms.
Seizures. Some people have had seizures while taking BETASERON, including people who have never had seizures before. It is not known if the seizures were related to MS, to BETASERON, or to a combination of both. If you have a seizure after taking BETASERON call your healthcare provider right away.
Blood Problems. You may have a drop in the levels of infection-fighting white blood cells, red blood cells, or cells that help you form blood clots. If drops in levels are severe, they can lessen your ability to fight infections, make you feel tired or sluggish or cause you to bruise or bleed easily.
Pregnancy:
Tell your doctor if you are pregnant or plan to become pregnant.
Most Common Side Effects:
The most common side effects of BETASERON include low white blood cell count, increases in your liver enzymes, headache, increase in your muscle tension, pain, rash, problems sleeping, stomach pain, weakness. These are not all the possible side effects of BETASERON.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Tell your healthcare provider about all the medicines you take and your medical conditions.
Please see the Full Prescribing Information and BETACONNECT™ Instructions for Use for additional information, and talk to your healthcare provider.
IMPORTANT SAFETY INFORMATION
Contraindications. BETASERON (interferon beta-1b) is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, Albumin (Human), mannitol, or any other component of the formulation.
Hepatic Injury. Severe hepatic injury including cases of hepatic failure has been rarely reported in patients taking BETASERON. In some cases, these events have occurred in the presence of other drugs or comorbid medical conditions that have been associated with hepatic injury. Consider the potential risk of BETASERON used in combination with known hepatotoxic drugs or other products (e.g., alcohol) prior to BETASERON administration, or when adding new agents to the regimen of patients already on BETASERON. Monitor patients for signs and symptoms of hepatic injury. Consider discontinuing BETASERON if serum transaminase levels significantly increase, or if they are associated with clinical symptoms such as jaundice.
Asymptomatic elevation of serum transaminases is common in patients treated with BETASERON. In controlled clinical trials, elevations of SGPT to greater than five times baseline value were reported in 12% of patients receiving BETASERON (compared to 4% on placebo), and increases of SGOT to greater than five times baseline value were reported in 4% of patients receiving BETASERON (compared to 1% on placebo), leading to dose-reduction or discontinuation of treatment in some patients. Monitor liver function tests.
Anaphylaxis and Other Allergic-Reactions. Anaphylaxis has been reported as a rare complication of BETASERON use. Other allergic reactions have included dyspnea, bronchospasm, tongue edema, skin rash and urticaria.
Discontinue BETASERON if anaphylaxis occurs.
Depression and Suicide. Depression and suicide have been reported to occur with increased frequency in patients receiving interferon compounds, including BETASERON. Patients treated with BETASERON should be advised to report immediately any symptoms of depression and/or suicidal ideation. Consider discontinuation of BETASERON if depression occurs.
Congestive Heart Failure. Monitor patients with pre-existing congestive heart failure (CHF) for worsening of their cardiac condition during initiation of and continued treatment with BETASERON. Cases of CHF, cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without known predisposition to these events, and without other known etiologies being established. In some cases, these events have been temporally related to the administration of BETASERON. Recurrence upon rechallenge was observed in some patients. Consider discontinuation of BETASERON if worsening of CHF occurs with no other etiology.
Injection Site Necrosis and Reactions. Injection site reactions occurred in 78% of BETASERON patients receiving BETASERON (compared to 26% on placebo) in controlled clinical trials with injection site necrosis reported in 4% of BETASERON patients (compared to 0% on placebo). For patients who continue BETASERON after injection site necrosis has occurred, BETASERON should not be administered into the affected area until it is fully healed. If multiple lesions occur, therapy should be discontinued until healing occurs. Patients should be advised of the importance of the use of aseptic technique and rotating injection sites.
Leukopenia. Leukopenia has been reported in 18% of patients receiving BETASERON (compared to 6% on placebo) in controlled clinical trials leading to a reduction in dose in some patients. Monitoring of complete blood and differential white blood cell counts is recommended. Patients with myelosuppression may require more intensive monitoring.
Thrombotic Microangiopathy. Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported several weeks to years after starting interferon beta products. Discontinue BETASERON if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
Flu-like Symptom Complex. Flu-like symptom complex for patients on BETASERON was 57% (versus 37% on placebo) in controlled clinical trials. Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms.
Seizures. Seizures have been temporally associated with the use of beta interferons.
Drug-induced Lupus Erythematosus. Drug-induced lupus erythematosus has been reported with interferon beta products, including BETASERON. Signs and symptoms of drug-induced lupus reported in BETASERON-treated patients have included rash, serositis, polyarthritis, nephritis, and Raynaud's phenomenon. Cases have occurred with positive serologic testing (positive anti-nuclear and/or anti-double-stranded DNA antibody testing). If patients develop new signs and symptoms of this syndrome, BETASERON therapy should be stopped.
Monitoring for Laboratory Abnormalities. In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and differential white blood cell counts, platelet counts and blood chemistries including liver function tests are recommended at one, three and six months after introduction of BETASERON therapy, and periodically thereafter in the absence of clinical symptoms.
Most Common Adverse Reactions. The most commonly reported adverse reactions (at least 5% more frequent on BETASERON than on placebo) in controlled clinical trials were injection site reaction (78% vs 26% for placebo), lymphopenia (86% vs 66%), flu-like symptoms (57% vs 37%), myalgia (23% vs 14%), leukopenia (13% vs 4%), neutropenia (13% vs 5%), increased liver enzymes (SGPT to greater than five times baseline value [12% vs 4%], SGOT to greater than five times baseline value [4% vs 1%]), headache (50% vs 43%), hypertonia (40% vs 33%), pain (42% vs 35%), rash (21% vs 15%), insomnia (21% vs 16%), abdominal pain (16% vs 11%), and asthenia (53% vs 48%).
Please see the Full Prescribing Information and BETACONNECT™ Instructions for Use for additional information, and talk to your healthcare provider.
