- Biosimilars designated as “interchangeable” are as safe and effective as their original biologic, and they undergo rigorous and thorough evaluation by the US Food and Drug Administration (FDA) before approval.
- Treatment costs are expected to decrease as biosimilars become more widely available.
- Patient education is extremely important, as biosimilars are a new concept.
- Lack of confidence in and knowledge of biosimilars among providers are barriers to their wider adoption.
- The VOLTAIRE-CD study demonstrated comparable safety and effectiveness between the adalimumab reference product Humira® and Cyltezo® (adalimumab-adbm), formerly known as BI 695501. The study revealed that patients who switched from Humira to Cyltezo maintained the therapeutic benefits, leading the FDA to approve Cyltezo as the first interchangeable biosimilar to Humira.
The incidence of inflammatory bowel disease (IBD) has increased globally,1 which has redirected the health care system’s focus toward safe and affordable pharmacologic interventions. As the patents of approved anti-tumor necrosis factor-α (TNF-α) drugs expire, biological copies of the approved products, known as biosimilars, have been and continue to be developed. Biosimilars are thoroughly vetted and approved on the basis of similarity to their reference product; however, many physicians hesitate to prescribe these drugs to their patients despite their potential to reduce treatment costs for many conditions.2
Michele Kissous-Hunt, PA-C, DFAAPA, is a faculty member in the Physician Assistant Program at the Touro Health School of Science in New York City, New York, and the former chair of the Crohn’s & Colitis Foundation (CCF) National Scientific Advisory Committee for the Nurse & Advanced Practice subcommittee. Ms Kissous-Hunt is also a sub-investigator on multiple IBD clinical trials and has published studies and lectured on IBD around the United States. In this article, Ms Kissous-Hunt discusses the use of biosimilars in treating patients with IBD and what both patients and providers should know regarding the emerging role of biosimilars in the treatment landscape.
Several biologics with an indication for IBD now have biosimilars on the market. Can you explain what a biosimilar is, the difference between a generic medication and a biosimilar, and how biosimilars are approved?
Biosimilars are biologic medications, meaning they are produced from living organisms and are very similar to an existing FDA-approved biologic medication. There are no clinically meaningful differences between a biosimilar and its reference product in terms of safety, purity, or potency.3 It takes approximately 5 to 10 years to develop a biosimilar, and it can cost significantly more than developing a conventional generic medication, which takes approximately 2 years to develop.4
In order for a biosimilar to be approved, an extrapolation from 1 indication for the biosimilar product to all the indications originally approved for the original biologic must be demonstrated through a totality of evidence, meaning it has to demonstrate structural similarity, similar immunogenicity and toxicity, and similar safety to the reference product.5
Patient education is important when beginning therapy with a biologic agent, and the whole concept of this type of treatment may be confusing. What role can clinicians, including physician assistants and nurse practitioners, take in furthering efforts toward patient education about biosimilars?
Since this is a very new concept to our patients, patient education is extremely important for biosimilars.6 As providers, we need to build patients’ confidence in their treatment by educating them early, especially if you are switching a patient from a reference product to a biosimilar. We need to discuss with patients that biosimilars are safe and effective biologic medications that are used to treat many chronic conditions, and that biosimilars do not have a different mechanism of action from its reference product.
When counseling patients about biosimilars, I want to make sure they understand that biosimilars are clinically equivalent and are not inferior to their reference product. We need to reassure them that they are getting a medication that is clinically equivalent with the same indications, mechanism of action, dosing, and monitoring for adverse events as its reference product.
Another important thing patients need to understand is that biosimilars may help increase access to medications; as biologics are very expensive, biosimilars will help spur price competition, and thus in the long run, they may increase product availability.7
Patients often have concerns about effectiveness and safety whenever new medicines are first introduced. A study found that most patients were not familiar with biosimilars, and those who were had doubts and concerns about their safety and efficacy.8 How can providers correct misperceptions about biosimilars, assure patients that these products are effective and safe, and involve patients in decision making concerning biosimilars in their treatment regimens?
Our main goal should be to build confidence by educating our patients at the onset. When patients are switching from a reference product to a biosimilar, providers should make sure that patients understand the rigorous process the FDA implements for a biosimilar to get approval. When counseling patients on the safety and efficacy of biosimilars, we need to first make sure that patients understand there is no clinically meaningful difference between the biosimilar and its reference product in terms of safety, purity, and potency; it must be clinically equivalent to its reference product.
Most importantly, we need to avoid causing delays in care because this can lead to adverse outcomes. Using shared decision making, we should assess patients’ values and preferences, compare treatment options, and discuss their preferences with them. We should also refer patients to reputable resources where they can become informed on biosimilars, such as the CCF,9 the American Gastroenterological Association (AGA),10 and the FDA.11
Some studies show that some providers hesitate to use biosimilars in the care of patients with IBD. In a study from 2020, 24% of IBD providers were either uncomfortable or very uncomfortable recommending biosimilars to their patients.12 How can providers educate themselves on the use of biosimilars to feel more confident when counseling patients?
Since that study was published, there has been growing acceptance of biosimilars among providers. The Cardinal Health 2023 Biosimilars Report — which surveyed more than 350 providers in rheumatology, gastroenterology, dermatology, and ophthalmology to assess the changing perspectives toward biosimilars — found that approximately 80% of gastroenterologists reported feeling at least somewhat comfortable switching from 1 biosimilar to another. However, only 61% of surveyed gastroenterologists believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.13
Providers need to educate themselves on the use of biosimilars by reviewing the most up-to-date information from the CCF, the AGA program for gastrointestinal clinicians, and the FDA. Providers must also familiarize themselves with the FDA definitions and understand the rigorous process and standards for approval that biosimilars have to meet so that they can feel comfortable discussing this with their patients and provide them with the necessary reassurances. Additionally, providers should be familiar with the key terms and concepts associated with biosimilars such as interchangeability, the biosimilar switch studies, and which biosimilars are currently available in the US.
Biosimilar switches are typically nonmedically needed switches. We should explain to our patients that the FDA guidance on biosimilar interchangeability is that [an interchangeable] biosimilar must produce the same clinical result as its reference product in any given patient based on an indication. Basically, if you make a switch, it should result in no difference to the patient in terms of effectiveness, safety, persistence of treatment, and immunogenicity.
Are there any specific counseling points you take into consideration when discussing biosimilar use with regards to refractory Crohn Disease in particular?
For a refractory Crohn’s patient, if I am planning to use an anti-TNF such as infliximab, during my discussion I will point out that their insurance might prefer that they take a biosimilar and make sure that they are familiar with the biosimilar names that are currently available. I will emphasize that biosimilars are clinically equivalent to the reference product and that we are not compromising their quality of care for cost of care, as clinical trials proved no difference in safety and immunogenicity between the biosimilars and the reference product in refractory Crohn’s patients, and the monitoring of their disease activity, adverse events and drug levels will not change. Most importantly, I would emphasize to them that we cannot delay their treatment in order to battle insurance, especially if the patient is sick, since the disease can continue to progress and this can result in complications and bad outcomes.
There are now several biosimilars on the market, and more will be coming in the future. Do you find the biosimilars to be interchangeable with each other, or have you noticed any differences? Have you found it necessary to switch biosimilars in some cases?
While not all biosimilars are considered interchangeable, there are studies and data that demonstrate that interchangeability is possible and safe. For instance, in the NOR-SWITCH trial (ClinicalTrials.gov identifier: NCT02148640), where 1 group continued using the reference drug infliximab and the other group switched to a biosimilar, the authors found there was no suggestion of differences in safety or immunogenicity between the 2 groups.14
Similarly, in the VOLTAIRE-CD study (ClinicalTrials.gov identifier: NCT02871635), which compared the adalimumab reference produce Humira with the adalimumab biosimilar Cyltezo (adalimumab-adbm), the authors found similar safety and efficacy between the 2 drugs and that treatment benefits were maintained in patients who switched from receiving Humira to Cyltezo.15
With this growing body of evidence, providers will eventually become more comfortable using biosimilars. Both providers and patients need to keep in mind that delaying treatment due to appeals may cause disease progression and complications, loss of response, and antibody formation. We need to make it clear to patients that our goal is to achieve and maintain remission, prevent disability, and improve their quality of life — not to fight for a specific brand name.
This Q&A was edited for clarity and length.
1. Wang R, Li Z, Liu S, Zhang D. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open. 2023;13(3):e065186. doi:10.1136/bmjopen-2022-065186
2. Najeeb H, Yasmin F, Surani S. Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients. World J Clin Cases. 2022;10(14):4327-4333. doi:10.12998/wjcc.v10.i14.4327
3. US Food and Drug Administration. Biosimilar basics for patients. Updated March 21, 2023. Accessed May 16, 2023. https://www.fda.gov/drugs/biosimilars/biosimilar-basics-patients
4. Eisenstein M. Bring on the biosimilars. Nature. 2019;569(7755):S2-S3. doi:10.1038/d41586-019-01401-5
5. Tesser JR, Furst DE, Jacobs I. Biosimilars and the extrapolation of indications for inflammatory conditions. Biologics. 2017;11:5-11. doi:10.2147/BTT.S124476
6. Maltz RM, McNicol M, Wingate L et al. There is no substitute for effective education about biosimilars. Crohns Colitis 360. 2021;3:otab047. doi:10.1093/crocol/otab047
7. Bhat S, Qazi T. Switching from infliximab to biosimilar in inflammatory bowel disease: a review of existing literature and best practices. Crohns Colitis 360. 2021;3(1):otaa093. doi:10.1093/crocol/otaa093
8. Peyrin-Biroulet L, Lönnfors S, Roblin X, Danese S, Avedano L. Patient perspectives on biosimilars: a survey by the European Federation of Crohn’s and Ulcerative Colitis Associations. J Crohns Colitis. 2017;11(1):128-133. doi:10.1093/ecco-jcc/jjw138
9. Crohn’s & Colitis Foundation. Biosimilars: what you should know. Accessed May 16, 2023. https://www.crohnscolitisfoundation.org/what-is-ibd/medication/biosimilars
10. American Gastroenterological Association. AGA GI Patient Center. Biosimilars. Accessed May 16, 2023. https://patient.gastro.org/biosimilars/
11. US Food and Drug Administration. Biosimilars: overview for health care professionals. Updated December 13, 2022. Accessed May 16, 2023. https://www.fda.gov/drugs/biosimilars/overview-health-care-professionals
12. Malter L, Jain A, Cohen BL, et al. Identifying IBD providers’ knowledge gaps using a prospective web-based survey. Inflamm Bowel Dis. 2020;26(9):1445-1450. doi:10.1093/ibd/izaa032
13. Cardinal Health. 2023 Biosimilars Report. Accessed May 16, 2023. https://www.cardinalhealth.com/en/product-solutions/pharmaceutical-products/biosimilars/biosimilars-report.html
14. Jørgensen KK, Olsen IC, Goll GL, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304-2316. doi:10.1016/S0140-6736(17)30068-5
15. Hanauer S, Liedert B, Balser S, Brockstedt E, Moschetti V, Schreiber S. Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(10):816-825. doi:10.1016/S2468-1253(21)00252-1
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Reviewed June 2023