Biosimilars & Switching

Infliximab, adalimumab, ustekinumab and other biologic medicines have transformed care for Crohn’s disease and ulcerative colitis, but they are expensive. Biosimilars are highly similar versions of these biologics that offer the same clinical benefits at lower cost. This article explains what biosimilars are, what “interchangeable” means in the United States, and how switching between biologics and biosimilars usually works in real-world IBD care.

Key Takeaways

• Biosimilars are highly similar to their reference biologic and have no clinically meaningful differences in safety or effectiveness.

• Interchangeability is a U.S. regulatory label about pharmacy substitution, not a higher-quality or “better” biosimilar.

• Large trials and many real-world IBD studies show that switching between originator biologics and biosimilars is safe and maintains disease control for most patients.

• Switching is usually planned with the gastroenterology team, and dosing, schedule, and monitoring usually stay the same.

• Insurance formularies and drug costs often drive switching decisions, which can be frustrating even when medical evidence supports the change.

Biosimilars in IBD: The Basics

Biologics are large, complex protein medicines made from living cells. They target specific immune pathways and are a major part of modern IBD treatment. Because they come from living systems, there is always some natural batch‑to‑batch variation, even within the same brand. (fda.gov)

A biosimilar is a biologic that is highly similar to an already approved biologic (the reference product) and has no clinically meaningful differences in safety, purity, or potency compared with that reference. (fda.gov)
To be approved, a biosimilar must:

• Use the same type of biological source

• Work through the same mechanism of action

• Be given in the same way, at the same strength and dosage form

• Have similar side effects and treatment benefits as the reference biologic (fda.gov)

Biosimilars vs generics

Generics are essentially identical copies of small‑molecule drugs, like many blood pressure pills. Biosimilars are different:

• Generics are chemically simple and can be copied almost exactly.

• Biologics are large, three‑dimensional proteins from living cells and cannot be duplicated exactly, so regulators focus on high similarity instead of perfect identity. (fda.gov)

In practice, for someone with IBD, an FDA‑approved biosimilar is expected to work just like its reference biologic in terms of benefits and risks.

How regulators test biosimilars

For a biosimilar, the goal is not to redo all the original clinical trials. Instead, the company must build a “totality of evidence” that compares the biosimilar to the reference product, including:

• Detailed structural and functional lab testing

• Pharmacokinetic and pharmacodynamic studies (how the drug moves and acts in the body)

• At least one clinical study to confirm similar safety and effectiveness

If that full package shows no clinically meaningful differences, the biosimilar can be approved for some or all of the same conditions as the reference biologic, even if IBD itself was not the main disease studied, as long as there is scientific justification. (fda.gov)

Interchangeability: What It Really Means

In the United States, “interchangeable biosimilar” is a special regulatory category created by law. All interchangeable products are biosimilars, but not all biosimilars are interchangeable.

Biosimilar vs interchangeable biosimilar

Both regular biosimilars and interchangeable biosimilars must show they are highly similar and have no clinically meaningful differences from the reference product. To get the interchangeable label, a company must provide extra data, often including switching studies where patients alternate between the reference product and the biosimilar. (fda.gov)

The key points:

• Interchangeability is mainly about automatic pharmacy substitution rules.

• It does not mean an interchangeable biosimilar is safer, more effective, or “higher quality” than other biosimilars. (fda.gov)

Pharmacy substitution and state laws

If a biosimilar is designated as interchangeable, a pharmacist may substitute it for the reference product without contacting the prescriber, depending on state pharmacy laws. (fda.gov)

For many IBD biologics that are infused in clinics, automatic substitution is less relevant, because infusion centers and specialists usually specify the exact product. Interchangeability matters more for self‑injected biologics that are dispensed at retail or specialty pharmacies.

Even without an interchangeability label, a gastroenterologist can prescribe a biosimilar in place of a reference biologic by name.

What the Evidence Shows About Switching in IBD

As biosimilars entered the IBD field, many patients and clinicians worried about loss of response or new side effects after switching. Over the past decade, a large body of research has addressed these questions.

A systematic review of 85 publications on switching between infliximab originators and biosimilars in IBD found:

• Clinical effectiveness after switching was similar to staying on the originator

• No new or unexpected safety issues appeared

• Rates of adverse events and treatment failure were in line with what is already known for infliximab itself (pubmed.ncbi.nlm.nih.gov)

Other long‑term cohort and non‑inferiority studies comparing patients who switched to infliximab biosimilars with those who stayed on the originator showed similar treatment persistence, disease control, and safety over several years. (pubmed.ncbi.nlm.nih.gov)

More recent work has even examined multiple switches, such as originator to biosimilar and then back again, with no significant changes in clinical disease activity or safety. (pubmed.ncbi.nlm.nih.gov)

Regulators also review broader safety data. FDA analyses report that switching between biosimilars and their reference products is not associated with higher risks of death, serious side effects, or stopping treatment compared with not switching. (fda.gov)

Major professional societies, including the American Gastroenterological Association, now state that, when approved through a rigorous pathway, biosimilars are expected to provide the same effectiveness and safety as their reference biologics for moderate to severe Crohn’s disease and ulcerative colitis. (gastro.org)

How Switching Usually Works in Practice

Reasons for switching

Common reasons someone with IBD might switch from a reference biologic to a biosimilar (or between biosimilars) include:

• Insurance formulary changes or step‑therapy rules

• Lower out‑of‑pocket costs or health‑system cost savings

• Hospital or clinic policies that standardize on certain products

• Rarely, supply issues with a specific brand

Occasionally, a switch may also happen for clinical reasons, such as wanting to re‑start therapy after a drug holiday at a different price point.

What typically stays the same

For most switches in IBD:

• The drug target and mechanism of action stay the same

• The route (intravenous infusion or subcutaneous injection) stays the same

• The dose and schedule are usually kept identical

• Monitoring plans (symptoms, labs, fecal calprotectin, sometimes drug levels) remain unchanged

Because of this, a well‑planned switch is usually more like changing manufacturers than starting a brand‑new treatment.

Monitoring after a switch

Care teams often:

• Document the exact product name and lot numbers

• Check symptoms and basic blood or stool markers after several doses

• Consider drug levels and antibody testing if disease control worsens

Research so far suggests that switching does not increase immunogenicity (antidrug antibody formation) beyond what is already typical for that biologic class, although monitoring remains important for everyone on biologics. (pubmed.ncbi.nlm.nih.gov)

Common Concerns

“Is an interchangeable biosimilar better than a regular biosimilar?”
No. Interchangeability is about whether a pharmacist can substitute at the pharmacy counter under state law. Both interchangeable and non‑interchangeable biosimilars must meet the same strict standard of biosimilarity and are expected to be as safe and effective as the reference biologic. (fda.gov)

“Can someone be switched without being told?”
Professional groups like AGA argue that stable patients should not be switched between products without involvement of their IBD specialist, even when payers or policies encourage non‑medical switching. (gastro.org)
In practice, notification rules vary by insurer, pharmacy, and state.

“What if symptoms seem worse after a switch?”
Some people report feeling worse after a change even when objective markers stay stable, sometimes described as a possible “nocebo” effect. Studies show that, on average, disease activity and drug levels remain similar after switching, but any new or worsening symptoms still deserve standard clinical evaluation, just as they would on the original biologic. (pubmed.ncbi.nlm.nih.gov)

Overall, current evidence and regulatory standards support biosimilars as reliable tools in the IBD treatment toolbox, with switching strategies that can preserve disease control while helping address cost and access barriers.