WHAT ARE BIOLOGICS AND WHAT ARE THEY USED FOR?
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. 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:
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.
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.
WHAT ARE THE POTENTIAL SIDE EFFECTS OF BIOLOGICS?
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.
WHAT ARE BIOSIMILARS AND HOW ARE THEY DIFFERENT FROM BIOLOGICS?
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’).
BIOLOGIC AND BIOSIMILAR REGULATION 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.
||Biologic Name Treatment (Indications*)
||Biosimilar Name Treatment (Indications*)
||Method of Administration
Moderate to severe Crohn’s disease (adult and pediatric), and ulcerative colitis (adult).
Used for patients who have not responded well to conventional therapies, or who have lost response to other biologics.
Moderate to severe Crohn’s disease (adult and pediatric), and fistulizing Crohn’s (adult and pediatric).
Moderate to severe ulcerative colitis (adult and pediatric).
Patients who have not responded well to conventional therapies.
Moderate to severe Crohn’s disease (adult), and fistulizing Crohn’s.
Moderate to severe ulcerative colitis (adult).
Moderate to severe Crohn’s disease (adult and pediatric), and fistulizing Crohn’s.
Moderate to severe ulcerative colitis (adult and pediatric).
Moderate to severe colitis (adults).
Used when conventional medicines have not worked or cannot be tolerated, or in patients who have demonstrated steroid dependence.
Moderate to severe Crohn’s disease and colitis (adults).
Used when conventional medicines have not worked well or cannot be tolerated, and in patients who have not had satisfactory response with infliximab.
|Antibody to the p40 subunit of IL-12 and IL-23
Moderate to severe Crohn’s disease (adults).
Used 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 by IV.
Subsequent doses by SC.
Subcutaneous injection (SC): A short needle is inserted into the layer of tissue between the skin and the muscle.
Intravenous injection (IV): 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 in the table.
Click on the drug name for a downloadable PDF of the product monograph: Humira, Remicade, Inflectra, Renflexis, Simponi, Entyvio, Stelara
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. Whether a biosimilar is interchangeable with its originator biologic is decided by each provincial health ministry. A physician may choose to switch their patient from an originator biologic to the biosimilar product if they think it will be beneficial. Until there is general consensus on the interchangeability of biologics and biosimilars among scientists, it is the position of Crohn’s and Colitis Canada that decisions about switching should be made by the physician and patient in consultation. Click here for Crohn’s and Colitis Canada’s full position statement on biosimilars or subsequent entry biologics (SEB’s).
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.
WANT TO LEARN MORE ABOUT BIOTHERAPIES?
Click here to watch our New and Emerging Treatments webinar to learn from experts in the field about biologic and biosimilar treatment options which have recently been made available.
More information about biologics is available in a downloadable brochure format.
To learn more about biosimilars, click here for a downloadable information sheet developed by the Gastrointestinal Society of Canada in collaboration with Crohn’s and Colitis Canada.