Biosimilars for Crohn’s Disease and Ulcerative Colitis

By Dr. Brian Bressler, MD, MS, FRCPC


What are biosimilars?

Biosimilars are a type of medication known as biologics. Biosimilars are produced once the patent for an original biologic (“originator” biologic) expires and new versions can be used in clinical practice. Like originator biologics, biosimilars are created using living tissues or organisms, such as bacteria, yeast, or human cell lines.

Biologics have much larger, more complex structures than typical simple medications known as “small molecule” drugs, such as aspirin and acetaminophen. Common small molecule pharmaceutical drugs and their generic forms are simple in structure and created from chemical reactions in a controlled laboratory setting.

Biologics, including biosimilars, effectively fight serious health conditions that may otherwise rely on less effective small-molecule treatments or have no available treatments at all.

Biosimilars become available once a patent for a biologic expires. Many new competitors can sell biosimilars for a fraction of the cost because expense dedicated to the research of the biosimilar is much cheaper. The high number of new biosimilars is one of the ways the cost for to life-altering therapies for people with devastating diseases can be reduced.

How long have biosimilars been around?

Biosimilars have been in Europe since 2006, Canada since 2009 and the US since 2015. There are currently more than 13 biosimilars approved in Canada and more than 22 approved in the US. They provide additional treatment options for many complex conditions, including Crohn’s disease, ulcerative colitis, diabetes, rheumatoid arthritis, cancer, osteoporosis, psoriasis and more.

Do biosimilars work?

Biosimilars can work just as well, and are just as safe, as their originators. They go through rigorous testing by the FDA, Health Canada and other government bodies around the world to demonstrate that there are no clinically meaningful differences in safety and efficacy between them.

What are the original biologics for Crohn’s and ulcerative colitis that their biosimilars are based on?

Biosimilars commonly used today for inflammatory bowel diseases are based on the medication infliximab. Remicade® is the original version of infliximab. Infliximab revolutionized the treatment of immune mediated diseases when it was first introduced as a medical treatment in 1998. It targets the tumor necrosis factor alpha (TNF-α) protein, a key part of the inflammatory processes associated with conditions like Crohn’s disease and ulcerative colitis. By binding to TNF-α, infliximab can reduce gastrointestinal inflammation that leads to uncomfortable symptoms and long-term damage.

The first biosimilars in North America were introduced and approved around 2015 after years of congressional review and approval in the US and Canada. Here are two of the common biosimilars used to treat IBD and that are both given by infusion:

  • Inflectra®: infliximab-dyyb, an infliximab biosimilar to Remicade manufactured by CELLTRION for Pfizer and approved by the FDA in 2016.
  • Renflexis®: infliximab-abda, an biosimilar to Remicade manufactured by Samsung Bioepis for Merck and approved by the FDA in 2017.

Adalimumab (Humira) is another biologic currently used for Crohn’s disease and ulcerative colitis that biosimilars will become available for in the future. First approved by the FDA in 2002, the full manufacturing and formulation rights to Humira will expire in 2023, paving the way for another possible biosimilar treatment for IBD.

Is there any difference in safety, efficacy or quality between biologics and their biosimilars?

Research shows that there’s no meaningful difference in safety, efficacy or quality between a biologic originator and its biosimilars. Here are some highlights from the research literature demonstrating that biosimilars are just as safe and effective as their biologic originators:

  • A 2014 review in BioDrugs of two clinical studies on an infliximab biosimilar called CT-P13 (sold as Inflectra) found CT-P13 just as effective as a long-term treatment for CD and other conditions like ankylosing spondylitis.
  • A 2017 study in the Journal of Crohn’s and Colitis found that CTP13 (Inflectra) to be just as safe and effective as Remicade.
  • A 2018 analysis in Best Practice & Research: Clinical Gastroenterology of data from people with UC who had taken CT-P13 (Inflectra) found that this biosimilar had proven to be just as safe.
  • A 2019 study in Annals of Internal Medicine of 5,050 people with CD found that CT-P13 (Inflectra) was just as safe and effective (defined as “equivalent,” or a 95% confidence interval of the hazard ratio) as infliximab, including the same likelihood of causing side effects.
  • A 2019 article in Annals of Internal Medicine found that biosimilars to infliximab for CD are just as effective as the original biologic, Remicade.
  • A 2019 study in Lancet of 220 people with CD found that CT-P13 (Inflectra) was just as safe and effective as Remicade, even when people were switched between the two or started with a different treatment and then switched to the other.

Keep in mind that biologics are made from the living cells using complex manufacturing processes that change over time. This means that there may be minor differences between different generations of an FDA-approved biologic. This is known as product drift: the Remicade or Humira that you took today may not be exactly the same as the Remicade or Humira you took five years ago. This happens because the organisms that make biologics naturally change from generation to generation as they grow, reproduce and die. Otherwise, the way the medication is structured chemically and functions medically are similar. And every single batch produced from a biologic originator is tested individually to make sure it meets the required standards.

FAQs for Crohn’s and UC

Here are some common questions you might have when you switch from an originator biologic to one of its biosimilars.

Are dosing and administration the same for biologics and their biosimilars?

Yes. Because biosimilars are nearly identical in structure and function to their biologic originators, you won’t need to change the dose you take or have it administered in any drastically different way. If you receive your biologic by infusion, you may need to go to a different infusion clinic.

Will I flare when I take biosimilars?

The likelihood of continuing to respond to a biologic should not depend on whether the version is the original one or the biosimilar one. Talk to your doctor or GI specialist about the effect that any biologic treatment for IBD has on your symptoms.

Are biosimilars safe and effective?

The safety profile of the biosimilar should be similar to that of the original biologic. Some of these biologics have been used for decades and are demonstrated to be safe and effective. Biosimilars are just as safe and effective as the originator biologics because of their similarity in structure and function.

Is it safe and effective to switch from Remicade to Renflexis or Inflectra?

Yes. If you’re taking Remicade without experiencing any major side effects or complications, then switching to Renflexis or Inflectra, two common biosimilars of infliximab, should not cause any new side effects or complications. In essence, biosimilars should work exactly the same as their biologic originators. Talk to your doctor or GI specialist if you’re not sure that the switch will be safe or effective for you.