Part 3: How Adalimumab Biosimilars Will Impact Clinicians

Readers can also check out part 1, part 2, part 4, podcast 1, and podcast 2 now.

As the US pharmaceutical sector prepares for at least 7 biosimilars for blockbuster originator Humira (adalimumab) to enter the market in 2023, management and encouragement of them will become a major priority for multiple stakeholders.

Clinicians will become the liaisons between payers and patients and may be tasked with having to manage multiple biosimilars for the same reference product, amid concerns over prescription changes. Additionally, different types of clinic staff could have different roles in promoting biosimilar utilization, and they all have power in ensuring patients are adequately educated on biosimilars.

This month, The Center for Biosimilars® is examining all aspects of what the launch of adalimumab biosimilars in the US market will mean for stakeholders, from lessons learned in other markets to the need to hear from providers who must decide whether to prescribe new products.

This third installment in a 4-part series will focus on how the launch of adalimumab biosimilars will impact different health care professionals within the clinic and pharmacy settings as well as how they can both encourage biosimilar use and improve patient care.

Providers

Providers may face challenges to prescribing biosimilars on several fronts. Payers and pharmacy benefit managers (PBMs) will have a big influence on which biosimilars, if any, are accessible to patients. They will act as levers on whether adalimumab biosimilars will be covered and whether they will be preferred over Humira. As has been seen in oncology, payer and PBM interference in prescribing decisions has long been an issue preventing biosimilar adoption.

PBMs also make decisions on which biosimilars are eligible for rebates and reimbursements, which have been known to shape payer policies and formulary decisions. Rebates, which are determined during negotiations between PBMs and drug companies, help payers save money on drugs. However, they are often greater for reference products and do not result in lower out-of-pocket costs for patients.

Reimbursements, or compensation given to a pharmacy or clinic for using a certain product, are agreed on by PBMs and payers and can impact providers. Again, however, this compensation does not result in lower drug prices for patients but can impact prescribing habits.

The biggest change that providers may see is that their patients’ prescriptions may change, and in some cases, they may not be made aware that a change has occurred.

Payers may not have policies in place to alert physicians that they are no longer covering the reference product or a particular biosimilar. A survey of medical oncologists published this summer found that providers were often unaware that their patients had been switched from a reference product to a biosimilar, which the investigators cited as a major ethical issue. Patients who experience a coverage switch may become emotionally distressed, and having a physician that understands why the switch occurred could mitigate patient concerns.

Interchangeability is another consideration. Several adalimumab biosimilars are expected to enter the market with an interchangeable designation, meaning that pharmacists may switch out a prescribed product for an interchangeable biosimilar without being required to ask a physician for permission.

However, in preparation, most states have passed laws that require pharmacists to inform patients and physicians that a substitution has occurred, and all states give physicians the ability to restrict interchangeability by writing “dispense as written” or “brand medically necessary” on a prescription. More information on which states have what interchangeability restrictions can be found in part 2 of this series.

Increased prior authorization (PA) requests could place added burdens on providers as well. PA requests have long been a barrier to biosimilar adoption, forcing patients to wait longer periods to receive their medications. According to a survey from the American Medical Association, most providers wait between 1 to 5 days to receive a decision on PA requests from payers.

Providers may also be tasked with supplying information on biosimilars to patients to prepare them for a changed prescription. Providers should make themselves familiar with the adalimumab products coming down the pipeline, the properties that differentiate them from each other, and the clinical evidence establishing the safety of biosimilars and the safety of switching to one. Rheumatologists should also keep up-to-date on any guidances on switching patients safely.

Practice Administrators

Along with keeping up with the launch dates for different adalimumab biosimilars, administrators will need to ensure that clinics are well prepared for the introduction of adalimumab biosimilars, meaning that clinics may have to undergo several policy changes regarding:

• Mitigating stocking and administration complications
• Educating staff and patients on biosimilars and incoming adalimumab products
• Managing medication switches and/or implementing automatic substitution policies

Prior to adalimumab, clinics have had to juggle up to 5 biosimilars for the same reference product (trastuzumab), all of which launched at different times, giving health care facilities more time to add biosimilars without causing much disruption to patient care. However, up to 10 adalimumab biosimilars are expected to launch within the same year, meaning that different strategies may be needed to ensure that biosimilars are managed properly.

In 2023, 1 adalimumab biosimilar (Amjevita) will launch in January. Between 5 and 9 (approved: Cyltezo, Hadlima, Hulio, Yusimry, Abrilada, Hyrimoz; under review: AVT02, Yuflyma, Idacio) will launch in July.

Stocking multiple biosimilars for the same reference product is a major concern for practices and pharmacies. Carrying a reference product along with several biosimilars could increase carrying costs. Additionally, biosimilars and reference products may have different storage properties, such as storage temperature requirements, shelf lives, light sensitivity, administration routes, and packaging.¹

Labels may also look alike because biosimilars will be listed with the same nonproprietary name as the reference product with different, but sometimes very similar, 4-letter suffixes added on to the end (ex. adalimumab-aqvh, adalimumab-adaz, adalimumab-adbm), which could create confusion and potentially lead to accidental administration of the wrong product or a product not covered by a patient’s insurance, creating additional costs and billing issues for the practice.

Clinic administrators may be tasked with curating biosimilar education materials for patients and other clinicians if they do not have them already. Administration teams could develop their own materials or collect existing materials. Notably, FDA has already warned 1 company about its education materials.

Administrators will also need to consider how to handle switches to biosimilars. In addition to formulary changes causing patients to receive different medications than they have received previously, clinics will have an opportunity to make biosimilars—and the savings that come with them—more accessible to patients by implementing automatic substitution policies.

Automatic substitutions, also known as therapeutic interchange, have been shown to increase biosimilar adoption and cut costs within oncology practices. These policies would enable pharmacists to substitute biosimilars for the reference product automatically without having to wait for a physician to approve it. Automatic substitution can act as a practice-level policy for interchangeability.

Three adalimumab biosimilars are expected to launch with an interchangeability designation (Approved: Cyltezo; Under review: Abrilada, AVT02) and 2 are expected to have this designation sometime after launching (Hadlima, Yuflyma). However, relying on interchangeability designations could restrict patient access to 5 other options, or in the states with laws completely restricting interchangeability (South Carolina, Indiana, Alabama, and Washington). Administrators can stay up to date with their state’s interchangeability laws by visiting, Cardinal Health’s Interchangeability Laws By State report.²

Nurses

Nurses can play a key role in helping patients gain comfort with adalimumab biosimilars. Patients may be wary about their prescriptions suddenly changing and nervous about what changing prescriptions could mean for their out-of-pocket costs and management of their conditions.

Whereas physicians will be responsible for managing prescription changes, nurses will be tasked with directly managing switches. Nurses are already highly familiar with administering medicines and managing and reporting adverse events, but they can also counsel and monitor patients, aid in maintaining patient adherence, and help develop guidances.

Studies have shown that nurses can also have a direct impact on helping to mitigate the nocebo effect from occurring by educating patients and increasing their confidence in the safety and efficacy of adalimumab biosimilars.

However, education for nurses is often ad hoc and incomplete, leaving many unaware of the differences between biosimilars and their references products. Nurses may not be fully briefed on certain aspects, such as interchangeability or pharmacovigilance.

Nurses should make themselves aware of what biosimilars are, how they differ from reference biologics, the safety of biosimilars, the safety of switching, and the rigorous approval process that each biosimilar has gone through to be FDA-approved to ensure that patients do not experience emotional distress from having their prescriptions change.

Additionally, there are some nurse-targeted guidances that address how to ensure that patients are switched from a reference product to a biosimilar safety, including the guidance developed by the European Specialist Nurses Organisation.

Overall, nurses will be the clinicians administering these biosimilars, and nurses, in addition to the patient, need to have confidence in what they are giving their patients.

Pharmacists

A paper published in Exploratory Research in Clinical and Social Pharmacy outlined several steps that clinical pharmacists can take to promote biosimilar utilization:³

• Weighing in on formulary decisions and encouraging the addition of biosimilars
• Assessing the credibility and reliability of biosimilar suppliers
• Conducting literature searches on the use of biosimilars in other health care facilities
• Conducting clinical trials to demonstrate comparable effects of biosimilars compared to reference products as part of a multidisciplinary team
• Directly managing the storage and dispensing of biosimilars
• Providing education to all health care stakeholders and policymakers

Additionally, clinical pharmacists can aid in the mission to improve patient confidence and acceptance of adalimumab biosimilars. A study published in Joint Bone Spine found that patients who had a consultation with a clinical pharmacist about biosimilars prior to meeting with a rheumatologist were significantly more likely to opt for a biosimilar over a reference product.

Pharmacists benefit from having a comprehensive understanding of the managed care landscape, making them well positioned to serve as champions for biosimilar use and driving adoption. Clinical pharmacists can also partner with physicians to develop efforts that can encourage adoption.

Pharmacists can advocate to administrators and other colleagues to support automatic substitution policies and advocate for health care reform. One pharmacist wrote to the editor of the Journal of Managed Care & Specialty Pharmacy, calling for pharmacists to speak out about the effect that health care reform proposals have on patient access to pharmaceuticals.

Finally, as medication experts, pharmacists can help lead education efforts and monitor the biosimilar pipeline for providers and other members of the health care team. Pharmacists can act as a source of truth and education to help develop confidence in biosimilars across the health care landscape.

The Monumental Task of Stakeholder Education

When it comes to the potential clinical and economic success of adalimumab biosimilars, education amongst all clinicians may become the first line of defense as all clinicians can ensure that patients are adequately educated on biosimilars. Patient education that is not sponsored by a drug company can be critical to ensuring that patients are accepting of biosimilars, clinical outcomes are maintained, and out-of-pocket costs decrease.

As mentioned above, patient education can help prevent the nocebo effect, which has been known to be the most common reason for patients with inflammatory bowel disease switching back to the reference product after being switched to a biosimilar, accounting for 75% of reverse switching cases.

To ensure that patient education is effective, education materials should be objective and clearly not developed by a pharmaceutical partner that is promoting their own product. Clinicians and patients need to have discussions surrounding all of the patients’ treatment options to ensure that patients are receiving the best possible care.

Additionally, clinicians themselves may need to have more biosimilar education, and education materials may need to be targeted differently between physicians, nurses, pharmacists, and administrators. One paper on the current state of provider education on biosimilars concluded that, “Education initiatives aimed at improving understanding of biosimilars should be viewed as the responsibility of all stakeholders in healthcare…While coordination across all these diverse groups is hardly feasible, cooperation and collaboration are encouraged whenever possible.”⁴

Increasing biosimilar education materials aimed at clinicians is a common strategy to improving provider confidence in the safety and efficacy of biosimilars. Some experts have said that provider education is the first step towards instilling patient confidence in biosimilars. However, a 2020 survey found that existing educational resources may not be adequately reaching clinicians.

Clinicians may have to search out biosimilar material if it is not already made available to them. A great introduction to the world of adalimumab biosimilars is to know what’s already approved and what’s coming, which can be found in the table provided in part 1 of this series.

Another place to go is the FDA website, which has an entire page with videos, infographics, fact sheets, and stakeholder toolkits for health care providers to learn about biosimilars. The International Generic and Biosimilar Medicines Association (IGBA) also has an education website promoting awareness of biosimilar products.

Another resource is the provider guidance created by Canadian rheumatology experts in 2020, which includes helpful tips for getting patients on board and comfortable with the idea of switching from a reference product to a biosimilar.

Additionally, clinicians can keep up to date with the latest clinical and real-world data that is constantly emerging about biosimilars, as well as the international data on the safety and efficacy of switching from Humira to adalimumab biosimilars. Administrators can also develop and curate biosimilar educational materials, such as pamphlets or packets, that can easily be distributed to other clinicians and patients.

Pharmacists should learn the nuances of adalimumab biosimilars, such as brand names, labels, concentrations, administration devices, interchangeability statuses, and which versions contain citrate, so as to ensure that patients are being distributed the correct product.

When it comes to the influx of adalimumab biosimilars coming, everyone in the clinic setting will have to do their part to make sure that savings are achieved and that patients are prepared.

References

1. Griffith N, McBride A, Stevenson JG, Green L. Formulary selection criteria for biosimilars: considerations for US health-system pharmacists. Hosp. Pharm. 2014;49(9):813-825. doi:10.1310/hpj4909-813
2. Biosimilar interchangeability laws by state. Cardinal Health. Updated July 2021. Accessed August 20, 2021. https://www.cardinalhealth.com/content/dam/corp/web/documents/publication/Cardinal-Health-Biosimilar-Interchangeability-Laws-by-State.pdf
3. Okoro RN. Biosimilar medicines uptake: the role of the clinical pharmacists. Explor Res Clin Soc Pharm. 2021;1:100008. doi:10.1016/j.rcsop.2021.100008
4. Oskouei ST, Kusmierczyk AR. Biosimilar uptake: the importance of healthcare provider education. Pharmaceut Med. 2021;35(4):215-224. doi:10.1007/s40290-021-00396-7