What Do Providers Need to Know About Biosimilars?

With a number of new biosimilars making their way to market and eventually to the clinic, it is crucial that healthcare providers become educated about and comfortable with biosimilar products. During a session at the fifth DIA Biosimilars Conference, held October 22 to 23 in London, United Kingdom, experts addressed a number of key areas for provider education.

Immunogenicity

Paul Chamberlain, an immunogenicity specialist at NDA Advisory Services, spoke to one of the biggest concerns for prescribers who are wary of biosimilars: immunogenicity. According to Chamberlain, it is critical to clarify the definition of immunogenicity, which is an undesirable host immune response to administration of a therapeutic agent. The innate immune response, the adaptive immune response, and immune tolerance are the key drivers of immunogenicity, and product factors (such as glycans, process-related impurities, or process changes) and patient factors (such as comorbidities or concomitant therapy) can impact the balance of those 3 factors.

While it is not feasible to predict how each factor might interact with others to affect immunogenicity, he explained, individual factors can certainly be controlled within acceptable limits. Furthermore, regulators look at both the individual and population level for immune response, and they also require a well-defined risk management plan for a product.

Thus, said Chamberlain, immunogenicity is “the wrong elephant in the room” for prescribers, because physicians typically conflate the incidence of antidrug antibodies (ADAs) with immunogenicity. “Please do not just use ADA rate … as a term which is equivalent to immunogenicity. It absolutely isn’t.”

To illustrate his point, Chamberlain gave the example of CT-P10; in looking at ADA titers between the biosimilar rituximab and its reference, regulators can see that while ADA rates for the 2 products may not appear comparable, the ADA titers overlap very closely. However, he said, few physicians see these reassuring data.

Unfortunately, he suggested, poorly founded fears about immunogenicity are impacting patient access. “Is the perception of immunogenicity-related risk a valid reason for restricting patient access to biosimilar medicines?” he asked.

Experience With Switching

Kristin Jørgensen, MD, PhD, a gastroenterologist at Akershus University Hospital, Norway, and one of the lead investigators of the NOR-SWITCH trial, presented lessons learned from the study that has become a touchstone for proponents of nonmedical switching.

Jørgensen reviewed the findings of NOR-SWITCH, which has been described elsewhere and found no meaningful differences in efficacy, safety, immunogenicity of reference infliximab and biosimilar CT-P13 in patients who switched.

However, beyond these findings, Jørgensen explained, NOR-SWITCH also produced data relevant to the nocebo effect; in terms of the patient global assessment, during the open-label extension, some patients felt that their disease worsened. The perceived worsening was not present in the physician global assessment, however.

In order to avoid the nocebo effect in her clinic today, Jørgensen focuses on education and building the provider—patient relationship. “We try to avoid this effect by informing them very well,” she said. “We know them, and that is an important point for us in our study.”

Focusing on education—“knowledge, knowledge, knowledge,” as she put it—“can reduce the perception gap that often exists between the physicians and the nurses and the patients.” In communicating about biosimilars, she said, positive framing and a unified voice across the center are crucial.

In looking toward the future, said Jørgensen, stakeholders should use caution in extending the findings of NOR-SWITCH to switching among reference products and multiple biosimilars: “Can we use the NOR-SWITCH data to say something about that? I don’t think we can at all,” she said, emphasizing that the number of new biosimilars entering the market poses a problem for clinicians in this regard.

To that end, a new study, NOR-MULTISWITCH, is in the planning stages. This trial will involve the reference infliximab and 3 biosimilars: CT-P13, SB3, and GP-1111.

Switching Management

Hanneke Voorneveld, a nurse practitioner of rheumatology at Maasstad Hospital in the Netherlands, and a member of the European Specialist Nurses Organisations (ESNO), discussed her experience in managing switches.

Traditionally, nurses have been trained to deliver and administer medicine and to manage and report adverse events (AEs), but in the context of switching, they can also counsel and monitor patients, as well as contribute to adherence, studies, education, and guideline development. Whereas physicians typically prescribe, nurses implement.

However, said Voorneveld, training for nurses on biosimilars is often both ad hoc and incomplete. Nurses may be unaware of complexities of using these new drugs, and may not be fully briefed on interchangeability or pharmacovigilance.

A nurse-led program is necessary to ensure continuity of information and education, and to ensure communication with patients. To that end, the ESNO has developed a guide for nurses on switch management. The guide, developed by the ESNO community, includes a pocket dictionary for nurses as well as frequently asked questions from patients and tips on how to address them.

The Promise of Biosimilars

Finally, Sam Khalil, PhD, worldwide head of medical affairs for Novartis, provided a reminder of the promise that biosimilars hold not just for health systems, but for patients’ well-being.

While cost savings and the increased access those savings can provide are the most frequently mentioned benefit of biosimilars, Khalil dove deeper into the implications of that increased access, asking, “Could this even help change the course of some disease, where biologics might not be needed in a chronic fashion, and we could stop them” after achieving disease control?

Currently, less than 10% of patients who need a biologic get one in the United States and the EU 5 nations, he explained, and most of the time, treatment guidelines are a key reason for that lack of access. While there may be no scientific reason to hold a biologic for a later line of treatment, costs pressures make trying small-molecule drugs first important.

However, delays in treating with biologics can lead to irreversible damage. Khalil pointed to ankylosing spondylitis as an example in which biologics are typically not used until radiographic evidence shows damage to the spine. “It’s complete nonsense, technically, but we had to do this” to keep down costs, he said. However, earlier treatment with a biologic could potentially preclude that damage in the first place.

Similarly, in the case of psoriasis, current research shows that skin cells have a memory linked to the interleukin-17A (IL-17A) pathway, and after psoriasis has progressed, discontinuing a biologic leads to the return of plaques.

However, starting IL-17A inhibitors earlier in the course of disease has been shown to lead, for 1 in 5 patients, to no relapse after 12 months without a biologic. “These are still low numbers, but interesting numbers,” he said. The correlating factor for patients who had clear skin without a biologic was the time of initiation versus disease duration, he explained.

According to Khalil, increased access to biologics through using biosimilars may have the potential to fundamentally change the course of diseases previously understood to be chronic, with substantial implications for patients’ quality of life and for the healthcare system as a whole.