Today in North America, Europe, and Asia, there are more biologics – originators and biosimilars – in use to treat inflammatory arthritis than in any other disease.

Over the past 24 years, biologics have become a life-saving treatment option for patients with serious chronic disease, including inflammatory arthritis patients, whose disease does not respond to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) such as methotrexate, hydroxychloroquine or sulfasalazine. 

Biologics are made from living organisms like yeast and bacteria. The first version of a biologic developed is known as the "originator". This is because they are the original version of a drug that a biosimilar is based on. Biologics are much larger and more complex in nature than conventional, small molecule medicines such as over-the-counter ibuprofen (e.g. Advil) or by-prescription methotrexate. Biologics are administered in two ways; by self-injection under the skin or into muscle, or by intravenous (IV) infusion into a vein in the hand, wrist or arm.

As patents expire for originator medicines, other manufacturers may produce new, similar versions shown to be as safe and effective. These new versions are called biosimilars.[1] Since the originator drugs are large and complex, biosimilars can be highly similar, but not identical.

Biosimilars have been approved for use in Canada since 2009 and for use in inflammatory arthritis since 2014. Fifty-five biosimilars are currently approved by Health Canada.

Generic medications are copies of brand-name medications, have the same active ingredient, and are the same as those brand name medications in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.

Biosimilars, like generic medications, are lower priced versions of brand name ("originator") medicines. Originator biologics have already set the foundation of research and development for biosimilars, which means biosimilars are more cost-effective to produce and lead to similar outcomes. But biosimilars are not the same as generic medicines because unlike non-biological medicines, biologics are often large and complex and cannot be exactly copied. 

There are very small differences between different batches of an originator biologic. This is because they are made using living organisms with some tiny natural differences. The same goes for the slight differences between a biosimilar and its originator, which are also not clinically meaningful.

The immune system has evolved to recognize foreign proteins in the body. Biologics are usually injected into the body and the immune system often reacts to them. This reaction is referred to as the immunogenicity of the product. Sometimes,  immunogenicity can only be detected using sophisticated laboratory tests and has no impact on the patient. In other cases, immunogenicity can impact patient safety or how well the medication works. For these reasons, studies showing that there are no clinically meaningful differences in immunogenicity between the biosimilar and originator are required for approval of a biosimilar. In addition, biosimilar manufacturers are responsible for monitoring the immunogenicity potential of the biosimilar after it is used in Canada.[1]

In Canada, interchangeability often refers to the ability for a patient to be changed from one drug to another equivalent drug by a pharmacist, without the intervention of the doctor who wrote the prescription when it has been deemed interchangeable by a Provincial or Territorial regulatory body. This is a common practice for drugs that are off patent and have been deemed interchangeable with their generic equivalent.

Health Canada has declared biosimilars not to be interchangeable with their originator. Health Canada's approval of a biosimilar is independent of provincial, territorial, or private drug plan decisions regarding its formulary listing and reimbursement or any decision as to interchangeability between these medications. According to the new guidance from Health Canada, interchangeability decisions rest with provincial or territorial governments. They also regulate pharmacy substitution practices.

Transitioning” or “switching” means a patient is moved from one medication to another. In the case of biologics, there are two types of transitions:

“Medical transition” occurs in the case of a patient not doing well on their current originator biologic or biosimilar biologic who is transitioned to another originator or biosimilar, based on a decision by the patient and their rheumatologist, in order to regain maximum disease control.

“Policy transition” (sometimes referred to as “non-medical switching”) occurs when a public or private drug plan’s reimbursement policy necessitate patients move from their current originator biologic to its biosimilar biologic.

For the past eight years, provincial drug plans across Canada have listed biosimilar brands ahead of originators for treatment-naïve patients (patients who have not previously received the originator). Since 2019, provincial and territorial drug plans, including Ontario, British Columbia, Quebec, Alberta, New Brunswick, Nova Scotia, Northwest Territories, Saskatchewan, Newfoundland and Labrador, Yukon, and Prince Edward Island have also begun implementing policies that transition patients from an originator to an equally safe and effective biosimilar approved by Health Canada.[1]

In the context of biosimilar use, Health Canada considers “switching between authorized products to refer to a change from routine use of one specific product to routine use of another specific product. Patients and health care providers can have confidence that biosimilars are effective and safe for each of their authorized indications. No differences are expected in efficacy and safety following a change in routine use between a biosimilar and its reference biologic drug in an authorized indication.”[2]

Under a transition policy, patients have a certain period to discuss with their prescriber transitioning from an originator to a biosimilar and get a prescription for the biosimilar to keep their drug plan coverage. Patients unable to transition to the biosimilar for medical reasons can make exceptional requests for continued coverage of the originator.

Prior to transitioning, both physicians and their patients must be fully informed and have all available information about the biosimilar medicine, such as details about the reimbursement policy, patient support program information, including contact names and phone numbers.

In the context of biosimilar use, Health Canada considers transitioning or “switching between authorized products to refer to a change from routine use of one specific product to routine use of another specific product. Patients and health care providers can have confidence that biosimilars are effective and safe for each of their authorized indications. No differences are expected in efficacy and safety following a change in routine use between a biosimilar and its reference biologic drug in an authorized indication.”[1]

Transitioning patients from originator biologics to biosimilar biologics is associated with the potential for a “nocebo” effect, a phenomenon that occurs when a patient’s negative expectation causes a treatment to have a more negative effect than it otherwise would—essentially, the opposite of the placebo effect.

The way in which rheumatologists and other health care providers communicate with patients about transitioning to a biosimilar is key to preventing the nocebo effect. Patients should be informed about the transition well in advance and the availability of research-based information is important for patient understanding and empowerment. Finally, an appointment with a rheumatologist to discuss biosimilar transitioning should ideally allow enough time for the patient to understand the concept of biosimilars and transitioning and to address any concerns properly.

Because of the way biosimilars are developed, it is not always necessary to carry out clinical studies with the biosimilar in all the diseases for which the originator has been shown to work. Instead, it may be possible to extend safety and efficacy data from studies in one disease to cover others. This is known as extrapolation or extension of indications. An indication is a term that means the use of a medicine to treat a specific disease. Many biologic medicines are approved for more than one indication.

Because a biosimilar is very similar in structure and function to an originator with proven safety and efficacy, clinical studies do not need to be repeated for each indication.

Patients and physicians can have confidence in the use of a biosimilar in each indication approved by Health Canada.