Biotherapies

Biotherapies are a class of drugs used to manage Crohn's or colitis that includes biologic and biosimilar medications. A biologic is a drug that is made from living cells. Vaccines, insulin, and monoclonal antibodies are examples of biologics. They have large, complex molecular structures. Some of the biologic medications are engineered to target specific activity in the immune system to treat inflammation. Biosimilars are drugs that are similar, but different than the originator biologic.

What are biologics?

Inflammation is the body’s normal response to things like injury, infection (e.g., bacteria, viruses), stress, and pain. For reasons not yet understood, sometimes the immune system does not function properly and causes damage to healthy tissue.

Biologics stop or reduce inflammation by blocking key cells or chemicals involved in triggering inflammation. In IBD patients, use of biologics blocks inflammation in the gut and allows it to heal. 

Biologics are generally administered under the skin by injection or intravenously by infusion. There are different types of biologics used to treat Crohn’s disease and ulcerative colitis.

ANTI-TNF Biologics 

One of the signals involved in causing inflammation in people with Crohn’s or colitis is called tumour necrosis factor alpha, or TNF-alpha. Biologic medications that block those signals are known as anti-TNF biologics.

α4β7 Integrin Blockers Biologics or selective adhesion molecule inhibitors (SAM)

These biologic medications block the attachment of white blood cells to tissues, preventing them from entering the lining of the gut and causing inflammation. 

Antibody to the p40 subunit of IL-12 and IL-23

IL-12 and IL-23 are messenger chemicals that recruit white blood cells into the gut to cause inflammation. Anti-p40 medications block the messenger signal of both IL-12 and IL-23 to reduce inflammation. 

In Canada, biologics can also be used as treatment for many other complex conditions, including arthritis, cancer, osteoporosis, psoriasis, HIV, multiple sclerosis, and more. If you have moderate to severe inflammatory bowel disease (IBD), you should discuss with your physician if biologic therapy is appropriate for you.


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How are biologics made?

With the use of biotechnology, specific cells isolated from living organisms are given a piece of DNA (gene) that codes for a specific protein. These cells will produce this specific protein in large amounts that can then be harvested for use as biologics in patients. 

Biologics tend to be higher in costs than simple small molecule drugs due to their complex manufacturing, transport, and administration. Manufacturers of biologics tend to offer a wide variety of support to patients, including coordination of injection/infusion services and assistance with reimbursement. 

Private insurers and public health programs can provide partial or complete financial coverage for biologics, depending on specific eligibility criteria. 


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Side effects and risks of use

All medications are associated with risk and benefits. Risks of using biologics may include injection or infusion site reactions, allergic reactions, and infection. Your doctor will work with you to determine proper dosage to help balance your symptoms and potential side effects.

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What are biosimilars?

As with other medicines, once a patent expires for a biologic, it is legal for other manufacturers to reproduce the drug. Most medicines, such as aspirin, are small molecule products, which mean they have simple molecular structures that are easy to reproduce or copy. Such copies are called generic drugs. By comparison, biologics are very large and have complex molecular structures.

It is impossible to produce an exact copy without using the exact same ingredients, the living cell lines, and manufacturing conditions. Therefore, the drug that is produced by another manufacturer can never be considered identical to the initial biologic and is referred to as a ‘biosimilar’ (and not a ‘generic’).

Click here for our Biosimilars infographic that explains the difference between biologic and biosimilar drugs.


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Regulation of biotherapies in Canada

Because biosimilars are not identical to originator biologics, Health Canada regulates biosimilars as new drugs and states clearly that biosimilars are not generic biologics. Health Canada only approves biosimilars for marketing in Canada when the manufacturer demonstrates that their product is of highly similar quality, safety, and efficacy (effectiveness) to their reference biologic drug.

Health Canada requires that there be no clinically meaningful differences in safety and efficacy. Currently, there are two IBD biosimilars approved by Health Canada, but additional biosimilars are expected in the near future, as the patents for innovator biologics continue to expire.

Click here to view our Biosimilars in Canada factsheet that provides expert answers to commonly asked questions about how biologic and biosimilar drugs differ, their safety of use and effectiveness, and non-medical switching in Canada. This pdf is downloadable and printer-friendly. 


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Medications available in Canada

Indications for the use of biotherapies (e.g., disease severity and or disease severity) may vary between originator and biosimilar drug. Product monographs are listed below and provide detailed descriptions of indications for each drug approved for treatment of IBD in Canada.

Anti-TNF

Drug Name: Adalimumab

Biologic Brand Name (Indications*): Humira®

  • Used for moderate to severe Crohn’s disease (adult and pediatric) and ulcerative colitis (adult).
  • Typically for patients who have not responded well to conventional therapies, or who have lost response to other biologics.
  • Subcutaneous injection (SC): To administer the drug a short needle is inserted into the layer of tissue between the skin and the muscle.

Product monographs provide detailed descriptions of indications for each drug listed in the table. Click here to download a PDF of the product monograph: Humira.

Biosimilar Brand Name: N/A

Drug Name: Infliximab®

Biologic Brand Name: Remicade​®

  • Used in patients with moderate to severe Crohn’s disease (adult and pediatric), fistulizing Crohn’s (adult and pediatric) and moderate to severe ulcerative colitis (adult and pediatric).
  • Typically for patients who have not responded well to conventional therapies.
  • Intravenous injection (IV): To administer the drug, a needle or tube is used to insert the drug directly into a vein.’

Indications may vary between originator and biosimilar drug. Product monographs provide detailed descriptions of indications for each drug listed here. Download a PDF of the product monograph: Remicade

Biosimilar Brand Name: Inflectra​®

  • Moderate to severe Crohn’s disease (adult), and fistulizing Crohn’s.
  • Moderate to severe ulcerative colitis (adult).
  • Intravenous injection (IV): To administer the drug, a needle or tube is used to insert the drug directly into a vein.’

Indications may vary between originator and biosimilar drug. Product monographs provide detailed descriptions of indications for each drug listed here. Download a PDF of the product monograph: Inflectra

Biosimilar Name: Renflexis​®

  • Used in patients with moderate to severe Crohn’s disease (adult and pediatric), fistulizing Crohn’s, and moderate to severe ulcerative colitis (adult and pediatric).
  • Intravenous injection (IV): To administer the drug, a needle or tube is used to insert the drug directly into a vein.’

Indications may vary between originator and biosimilar drug. Product monographs provide detailed descriptions of indications for each drug listed here. Download a PDF of the product monograph: Renflexis

Drug Name: Golimumab 

Biologic Name: Simponi®

  • Used in patients with moderate to severe colitis (adults).
  • Typically when conventional medicines have not worked or cannot be tolerated, or in patients who have demonstrated steroid dependence.
  • Subcutaneous injection (SC): To administer the drug, a short needle is inserted into the layer of tissue between the skin and the muscle.

Product monographs provide detailed descriptions of indications for each drug listed in the table. Click here to download a PDF of the product monograph: Simponi.

α4 β7 Integrin Blockers

Drug Name: Vedolizumab

Biologic Name: Entyvio​®

  • Used in patients with moderate to severe Crohn’s disease and colitis (adults).
  • Typically when conventional medicines have not worked well or cannot be tolerated, and in patients who have not had satisfactory response with infliximab.
  • Intravenous injection (IV): To administer the drug, a needle or tube is used to insert the drug directly into a vein.’

Product monographs provide detailed descriptions of indications for each drug listed in the table. Click here to download a PDF of the product monograph: Entyvio

Antibody to the p40 subunit of IL-12 and IL-23

Drug Name: Ustekinumab

Biologic Brand Name: Stelara®

  • Used in patients with moderate to severe Crohn’s disease (adults).
  • Typically when conventional therapies have not worked or cannot be tolerated, or in patients who have failed or were intolerant to treatment with one or more TNF blockers.
  • First dose is by intravenous injection (a needle or tube is used to insert the drug directly into a vein). Subsequent doses by subcutaneous injection (a short needle is inserted into the layer of tissue between the skin and the muscle).

Product monographs provide detailed descriptions of indications for each drug listed in the table. Click here to download a PDF of the product monograph: Stelara


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Switching and interchangeability

Typically, if a patient has a prescription for a small molecule medication, a pharmacist is authorized to substitute a generic version without consulting with the patient’s physician. This is called interchangeability. The provincial health ministries decide whether to require interchangeability in their respective provinces. 

Some provincial governments are implementing or considering implementing interchangeable policies with biologics. It is the position of Crohn’s and Colitis Canada that decisions about switching from a biologic to a biosimilar should be made by the physician and patient in consultation. 

Click here to learn more about our legal/ethics review, evidence review, and position statement.

We think that treatment decisions should be made between you and your doctor. Policy change made at the expense of your health is not okay. 

If you agree, click here to take part in our letter-writing campaign to let your local government representative know how you feel!


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Immunogenicity

Individuals doing well on a biologic innovator drug should be aware of the risks and benefits of substituting the innovator drug with its biosimilar. Because biologics are ‘foreign’ proteins that were not produced by the patient’s own genes, the body can develop antibodies to the biologic over time.

This immune response is called immunogenicity. Once antibodies to a biologic are formed by a patient’s body, the biologic may stop working or cause an allergic-like reaction. Whether immunogenicity is made more likely by switching among biologics and biosimilars remains unclear.

Some researchers believe that there is sufficient clinical evidence to suggest that switching does not increase or accelerate immunogenicity while others believe that more rigorous clinical studies are required.


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Therapeutic Drug Monitoring

What is therapeutic drug monitorting?

Therapeutic drug monitoring is used with biologic drugs such as infliximab. With these new medications, some patients have a great response at first, but over time they lose the response and the medication doesn’t work as well as it used to.

Blood Tests

Biologics are given as an injection or infusion every few weeks. When the drug is first given, its level in the blood jumps up to what we call a “peak,” and over time that level drifts down to what we refer to as a “trough.” Then another dose is given and the level jumps up again. 

The trough level of a drug, just before the next dose, is actually very important and can help predict how well your disease is controlled. Patients who still have good levels of medication right before they get their next dose tend to do better than patients whose medication level is depleted before the next dose. 

People tend to clear out drugs from their system at different speeds. Some people actually make antibodies against the biologic which clears the drug out faster. If they clear out the drug too quickly, there is no drug left in their system and hence it cannot do its job very well. 

The doctor can test for both the level of drug immediately before the next dose, as well as whether the patient’s body has made antibodies against that drug. If the patient has a low level of drug and is not making antibodies, there is some other reason the drug is clearing out quickly, and the physician can help by giving more medication. 

If, on the other hand, there is a low level of drug and your body is making antibodies, there is probably no point continuing with that particular drug and it might be time to switch to a different medication. Also, if the drug level is high before the next infusion but the disease is not well-controlled, it might be time to switch medications.

Fecal calprotectin

Calprotectin is a protein found in white blood cells. When there is inflammation in your intestines, white blood cells will go to that area. When the white blood cells fight inflammation, they release their contents, including calprotectin. This results in higher levels of calprotectin in your stool. This test not only shows if there is inflammation; it can also measure how severe the inflammation is.

Fecal calprotectin is a very practical test where the stool sample can be collected at home and mailed to the lab. For patients who know they have IBD, this test can be used to find out if their disease is active or under control.

The test is often used when a patient begins a new treatment, to see if it is working, as opposed to doing a colonoscopy. The test can also help determine which patients need to undergo further testing using colonoscopy.

For more information, please visit our Stool Tests page.


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Additional Resources

Factsheet: Biosimilars in Canada

Our experts answer your questions about biologics and biosimilars! Please click here for our factsheet that covers how biologic and biosimilar drugs differ, safety and effectiveness of use, and non-medical switching in Canada.

Infographic: Biotherapies 101 

Flip through our infographic below to learn about how biologic and biosimilar medications are similar, but different. You can also download a PDF copy here.


Video: Biologics and Inflammatory Bowel Disease

Watch the video below to learn from an expert gastroenterologist about biologic medications for IBD. 

 

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