Report: Physician-Patient Education Can Improve Biosimilar Acceptance

Biosimilar uptake would be more successful and swifter if efforts were made to educate patients and providers about them, wrote Sonia T. Oskouei, vice president of Biosimilars for Cardinal Health, and Andrew R. Kusmierczyk, supervisor of Chemistry, Manufacturing, and Controls at Cardinal, in a new paper.

“In order to overcome any potential hesitation with biosimilars from a scientific or clinical standpoint, education will need to be at the forefront,” they said.

According to the review, the top reasons physicians and patients resist using biosimilars include:

• Immunogenicity – This is the tendency of a biologic to provoke an immune reaction that could change the clinical profile of the drug, although “the risk of immunogenicity with switching to a biosimilar has not been shown to be any greater than switching between 2 batches of any [originator] biologic,” the authors said. More evidence would be helpful in addressing provider concerns about immunogenicity.
• Regulatory requirements – In its approval pathway, the FDA stresses physicochemical characterization of the biosimilar molecule, or “analytical studies,” and underweights clinical efficacy trials, which are less helpful in validating biologic equivalence. Physicians, traditionally reliant on clinical studies, need to be educated on the scientific rigor behind the analytical rationale.
• Extrapolation – Biosimilar developers usually obtain approval for just 1 indication of an originator biologic, and after that the FDA is OK with doctors using biosimilars for all approved indications of an originator. “Studies have revealed greater provider hesitation with biosimilar utilization in indications that were granted via extrapolation,” the report stated. Giving physicians more training on critical quality attributes that justify biosimilar approval would alleviate these concerns.
• Interchangeability – Biosimilar developers can obtain interchangeability designations for their products, allowing pharmacists to make biosimilar substitutions without physician intervention. “Interchangeability is a regulatory designation, not a clinical one,” the report noted. Education can reinforce the concept that there are no clinical differences between biosimilars and interchangeables.

The report said education can be a powerful factor in getting physicians to employ biosimilars, noting the difference over time in survey responses from gastroenterologists in Europe who were asked to describe their confidence in biosimilars.

In a 2013 study, the majority reported little or no confidence in these agents. Yet, following an extensive EU effort to increase biosimilar knowledge, a 2015 survey revealed “drastic changes” in gastroenterologist attitudes: “47% of respondents felt either totally or very confident with biosimilars in 2015 compared with only 13% in 2013,” the report stated.

“Moreover, the 2015 survey revealed more than a 50% reduction in safety concerns with immunogenicity associated with biosimilars,” Oskouei and Kusmierczyk wrote.

Market adoption of infliximab biosimilars in the European Union also picked up, giving these agents a 50% share of the infliximab market (vs the originator biologic) by 2017, they said.

US Biosimilar Attitudes Improve

In the United States, the signs are that understanding and acceptance of biosimilars among rheumatologists has improved significantly.

A 2016 survey of US physicians (N = 102) who were mainly rheumatologists indicated that just 38% described themselves as “extremely familiar with the FDA’s definition of biosimilars,” which is that a biosimilar is “highly similar to and has no clinically meaningful difference from an existing FDA-approved reference product.”

A study of rheumatologists in 2019 (N = 320) found that 83% were “very familiar” with the FDA’s biosimilars definition. However, just 34% said they were likely or very likely to switch patients not doing well on the reference product to a biosimilar, which suggests that “a not-insignificant number of US rheumatologists still have knowledge gaps on the concept of biosimilarity,” Oskouei and Kusmierczyk said.

On the patient side, efforts need to be made to overcome the “nocebo effect,” they said. Patients often have never heard about biosimilars and, of those, not all would be confident about using one even if recommended by their physician.

When patients lacking confidence are treated with biosimilars, there is a documented potential for treatment to fail, and this is described as the nocebo effect. “The magnitude of this effect is not fully understood and could vary with disease state, but several recent studies on infliximab and etanercept biosimilars suggest an effect on the magnitude of 1 in 8 patients,” they wrote.

Negative outcomes from use of biosimilars can feed negative perceptions about them and add to physician and patient hesitancy to use these agents—another reason why efforts have to be made to overcome nocebo through education.

“The importance of patient education to mitigating the effect has been recognized and researchers are beginning to be able to measure its impact,” Oskouei and Kusmierczyk said.

Overall, in the struggle to boost acceptance via education, data can play a major role. “Data are always the best argument and continued evidence development is rightfully at the top of the list of action items,” they wrote.

Other report recommendations include:

• Standardized treatment guidelines – These would help to convince providers about the value of biosimilars and would also work by playing on the leverage that comes from peer confidence. By following good standards, physicians would achieve better outcomes and thereby improve their faith in these products.
• Start education early – Data indicate that younger health care providers are less familiar with biosimilars and less likely to prescribe them, so biosimilar education programs during medical training could improve usage. Further, teaching the general public about biosimilars could prepare them to be more accepting of biosimilars if they become patients.
• Patient messaging – Messaging tools with appropriate language can be effective in addressing patients’ concerns.
• Power of nurses – Nurses have been shown to be very influential when it comes to educating and reassuring patients about biosimilars.