Biosimilar Safety in Pregnancy
Learn how these new biologic drugs compare with existing ones, and whether they should be taken during pregnancy or breastfeeding.
By Mariah Z. Leach | March 17, 2023
Managing your arthritis or other rheumatic and musculoskeletal disease during pregnancy is critical, but not all arthritis medications are safe for a developing fetus. According to guidelines by the American College of Rheumatology, people who take biologic medications that block tumor necrosis factor, called “TNF inhibitors,” should continue taking them during pregnancy and breastfeeding. These include infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi, Simponi Aria), and certolizumab (Cimzia).
In recent years, however, new, competitive drugs, called “biosimilars,” have become available in the U.S. Significantly, at least eight new competitors to adalimumab (Humira) are being introduced this year since its patent expired. Other biosimilars that have been available in this country for rheumatic diseases are infusions, so patients may not know they are receiving one instead of their usual medication. Humira biosimilars, on the other hand, are self-injectible, so people will be aware they are receiving a different drug. And that raises questions about safety and effectiveness — especially for women who are pregnant or breastfeeding.
Biologic vs. Biosimilar
Name-brand biologics, known as the “reference” or “originator” products, have been on the market since the late 1990s. Biosimilars entered the U.S. market in 2016.
“A biosimilar is a biologic medication that is highly similar in function, potency, and toxicity to the reference biologic,” explains Amy Kehl, MD, a rheumatologist with Providence St. John’s Physician Partners in California. According to Dr. Kehl, “there does not appear to be clinically meaningful differences as far as safety or effectiveness of biosimilars.”
A number of biosimilars have been approved by the Food and Drug Administration (FDA), but various patent and other legal blocks kept most of them off the market in the U.S. — although they have been in use in other countries for years.
Biosimilars are not the same as “generic” medications. Generics are exact copies of chemically synthesized medicines. Biosimilars, on the other hand, are copies of reference biologics, which are very large and complex molecules made in living microbes. Due to their complexity and the use of living sources, biosimilars are “highly similar” but not exact copies. Before a biosimilar can be FDA-approved, the Biologics Price Competition and Innovation Act (BPCIA) of 2010 requires the medication to meet rigorous criteria.
“Interchangeable” Biosimilars
The BPCIA also includes a provision called “interchangeability.” If the biosimilar manufacturer can demonstrate no increased safety risk or reduced effectiveness when a patient switches multiple times between the reference product and the biosimilar, the biosimilar can be deemed “interchangeable.” In certain states, laws allow pharmacists to exchange a prescribed reference biologic for an interchangeable biosimilar without a health care provider’s approval or even making the patient aware of the substitution.
Biosimilars and Pregnancy
As more biosimilars come to the market, potentially driving prices down, insurance companies may require patients to use them rather than the name-brand reference biologic. So what does this mean for patients who are pregnant, planning to become pregnant or breastfeeding?
Dr. Kehl emphasizes the importance of maintaining disease remission during pregnancy, not only for the well-being of the mother but also the health of the pregnancy. “Limited data regarding biosimilars in pregnancy suggests that they are safe to use," she says. "However, data is limited regarding biosimilars in pregnancy. If there was no choice to use the originator biologic and there are risks of flare-ups of the underlying autoimmune disease, I would consider using an interchangeable biosimilar with the understanding that maintaining disease remission during pregnancy is important to not only the well-being of the mother but also pregnancy outcomes.”
A small study by researchers at University College London Hospital in the United Kingdom reviewed data on 18 women who had been taking TNF inhibitors when they became pregnant. “Biosimilar therapy was not associated with congenital abnormalities, preterm birth or other adverse pregnancy outcomes,” they concluded in Obstetric Medicine, published in 2022. Stopping biologics, however, was associated with preterm birth and disease flares.
Some experts are less comfortable with the idea of biosimilar use during pregnancy, such as Christina Chambers, PhD, MPH, a perinatal epidemiologist and professor of Pediatrics and Family and Preventive Medicine at the University of California San Diego. “We are studying pregnancy outcomes with exposure to biologic drugs, but we don’t have any studies on biosimilars yet,” she cautions. “In the case of generic, small-molecule drugs, we would not think the safety issues would be any different for the brand vs. the generic because the active ingredients are identical, but I don’t know if the same would apply to biosimilars. It does make sense for biosimilars to be studied separately since they are not identical to the [reference] biologic.”
More Information
If you have questions or concerns about the use of biosimilars while pregnant or breastfeeding, MotherToBaby may have answers. MotherToBaby provides “evidence-based information for moms and their providers about any exposures in pregnancy and breastfeeding to help prevent birth defects, developmental delays, and other adverse outcomes for both mom and baby,” says the organization’s president, Alfred Romeo, RN, PhD. “The research-based information we provide is carefully reviewed,” he adds. “Some of our members conduct the studies … some work at other health centers, and some manage the different databases like LactMed and Reprotox, so we use and manage a variety of resources to arrive at the best answers possible.”
Managing your arthritis or other rheumatic and musculoskeletal disease during pregnancy is critical, but not all arthritis medications are safe for a developing fetus. According to guidelines by the American College of Rheumatology, people who take biologic medications that block tumor necrosis factor, called “TNF inhibitors,” should continue taking them during pregnancy and breastfeeding. These include infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi, Simponi Aria), and certolizumab (Cimzia).
In recent years, however, new, competitive drugs, called “biosimilars,” have become available in the U.S. Significantly, at least eight new competitors to adalimumab (Humira) are being introduced this year since its patent expired. Other biosimilars that have been available in this country for rheumatic diseases are infusions, so patients may not know they are receiving one instead of their usual medication. Humira biosimilars, on the other hand, are self-injectible, so people will be aware they are receiving a different drug. And that raises questions about safety and effectiveness — especially for women who are pregnant or breastfeeding.
Biologic vs. Biosimilar
Name-brand biologics, known as the “reference” or “originator” products, have been on the market since the late 1990s. Biosimilars entered the U.S. market in 2016.
“A biosimilar is a biologic medication that is highly similar in function, potency, and toxicity to the reference biologic,” explains Amy Kehl, MD, a rheumatologist with Providence St. John’s Physician Partners in California. According to Dr. Kehl, “there does not appear to be clinically meaningful differences as far as safety or effectiveness of biosimilars.”
A number of biosimilars have been approved by the Food and Drug Administration (FDA), but various patent and other legal blocks kept most of them off the market in the U.S. — although they have been in use in other countries for years.
Biosimilars are not the same as “generic” medications. Generics are exact copies of chemically synthesized medicines. Biosimilars, on the other hand, are copies of reference biologics, which are very large and complex molecules made in living microbes. Due to their complexity and the use of living sources, biosimilars are “highly similar” but not exact copies. Before a biosimilar can be FDA-approved, the Biologics Price Competition and Innovation Act (BPCIA) of 2010 requires the medication to meet rigorous criteria.
“Interchangeable” Biosimilars
The BPCIA also includes a provision called “interchangeability.” If the biosimilar manufacturer can demonstrate no increased safety risk or reduced effectiveness when a patient switches multiple times between the reference product and the biosimilar, the biosimilar can be deemed “interchangeable.” In certain states, laws allow pharmacists to exchange a prescribed reference biologic for an interchangeable biosimilar without a health care provider’s approval or even making the patient aware of the substitution.
Biosimilars and Pregnancy
As more biosimilars come to the market, potentially driving prices down, insurance companies may require patients to use them rather than the name-brand reference biologic. So what does this mean for patients who are pregnant, planning to become pregnant or breastfeeding?
Dr. Kehl emphasizes the importance of maintaining disease remission during pregnancy, not only for the well-being of the mother but also the health of the pregnancy. “Limited data regarding biosimilars in pregnancy suggests that they are safe to use," she says. "However, data is limited regarding biosimilars in pregnancy. If there was no choice to use the originator biologic and there are risks of flare-ups of the underlying autoimmune disease, I would consider using an interchangeable biosimilar with the understanding that maintaining disease remission during pregnancy is important to not only the well-being of the mother but also pregnancy outcomes.”
A small study by researchers at University College London Hospital in the United Kingdom reviewed data on 18 women who had been taking TNF inhibitors when they became pregnant. “Biosimilar therapy was not associated with congenital abnormalities, preterm birth or other adverse pregnancy outcomes,” they concluded in Obstetric Medicine, published in 2022. Stopping biologics, however, was associated with preterm birth and disease flares.
Some experts are less comfortable with the idea of biosimilar use during pregnancy, such as Christina Chambers, PhD, MPH, a perinatal epidemiologist and professor of Pediatrics and Family and Preventive Medicine at the University of California San Diego. “We are studying pregnancy outcomes with exposure to biologic drugs, but we don’t have any studies on biosimilars yet,” she cautions. “In the case of generic, small-molecule drugs, we would not think the safety issues would be any different for the brand vs. the generic because the active ingredients are identical, but I don’t know if the same would apply to biosimilars. It does make sense for biosimilars to be studied separately since they are not identical to the [reference] biologic.”
More Information
If you have questions or concerns about the use of biosimilars while pregnant or breastfeeding, MotherToBaby may have answers. MotherToBaby provides “evidence-based information for moms and their providers about any exposures in pregnancy and breastfeeding to help prevent birth defects, developmental delays, and other adverse outcomes for both mom and baby,” says the organization’s president, Alfred Romeo, RN, PhD. “The research-based information we provide is carefully reviewed,” he adds. “Some of our members conduct the studies … some work at other health centers, and some manage the different databases like LactMed and Reprotox, so we use and manage a variety of resources to arrive at the best answers possible.”
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