Mandatory Switching of Biologic Drugs? Beware of Potential Side Effects
Over the last few decades, biologic drugs have gradually been added to physicians' therapeutic armamentarium. In the past five years, more than 60 of these new drugs have been marketed in Canada (Parliamentary Budget Officer 2019). They are used to treat a variety of serious and disabling illnesses including diabetes, immune system disorders and even cancer. Their arrival on the market is very good news for patients, as these medications – often prescribed as a last line of treatment when other therapies have failed – keep them active and help to significantly improve their health conditions and quality of life.
Biologic Drugs versus Biosimilars
As biologic drugs are produced from living cells rather than by chemical synthesis, their development and the manufacturing processes involved are considerably more complex and, therefore, more expensive than for traditional drugs. Quality control is even more critical and complications in production, potentially more catastrophic. Unlike chemical drugs, biologic drugs do not have fully defined and reproducible structures, making it impossible to create identical copies. Health Canada allows drugs called “biosimilars” – similar versions but not exact copies of biologic drugs – to enter the market only after the patent on the original version of the biologic drug – also known as the brand-name or “reference” biologic – has expired, and the similarity of the two products in terms of both safety and efficacy has been established.
In an effort to lower pharmaceutical spending, provincial governments have recently taken measures to foster the uptake of biosimilars as alternatives to the reference biologics. British Columbia set a precedent in May, 2019, by becoming the first province to introduce a mandatory biosimilar switching program for non-medical reasons (Grant 2019). In the first phase of the program, patients covered under the public drug plan, who were undergoing treatment with the original versions of the medications infliximab and etanercept and the insulin glargine, were forced to switch to biosimilar versions, even if they were in remission and their health condition was stable.
Alberta will go even further. As of January 15, 2021, patients who require a biologic medication for the first time will have to begin their therapy with a biosimilar, as reference biologic drugs will no longer be publicly covered. Patients currently taking a reference biologic, for which a biosimilar version exists, will be required to make the switch before that date in order to maintain their public coverage for the drug. Other provinces have adopted, or are considering adopting, similar mandatory switching policies aimed at prioritizing the public reimbursement of biosimilar drugs over reference biologics (Jeremias 2020).
Is Non-Medical Switching Well Advised?
The Institut national d’excellence en santé et services sociaux (INESSS) conducted an exhaustive literature review at the beginning of the year on the impacts of mandatory biosimilar switching policies. This review highlighted that for certain populations or certain therapeutic fields "very little or no data are available on the safety of switching a biological drug" (INESSS 2020). It urges decision makers to be cautious by reminding them that mandatory switching for non-medical reason is generally not accepted by scientific societies and clinicians. It is feared that patients who have few treatment options and whose conditions are complex may be destabilized (INESSS 2020).
In the vast majority of European countries, the decision to change a patient's medication to a biosimilar is made by the treating physician (Reilly and Schneider 2020). Changing a patient's medication to a biosimilar for strictly economic reasons is not authorized except in a few countries. It is accepted that the treating physician is better able to assess the needs and health conditions of his or her individual patients, and prescribe the drugs needed to adequately address them.
Mandatory switching for non-medical reasons ignores the fact that not all patients respond in the same way to medications, and can lead to additional costs to healthcare systems. In Denmark, where a biosimilar switching program has been set up, researchers recently found that healthcare use (+8%) and total healthcare costs (+7%) have increased for patients with chronic inflammatory diseases treated with etanercept (Glintborg et al. 2019). A previous study by the same researchers showed that 45% of the patients followed had increased healthcare use after the switch of infliximab with a biosimilar. On average, the number of service days per patient increased by 7.4% after the mandatory drug switch (Glintborg et al. 2018).
The cost savings that can be generated by biosimilar drugs are also not assured when they require higher doses to achieve the same clinical endpoints. This was highlighted by Italian researchers who compared two groups of patients with renal failure requiring hemodialysis treatments. Patients who switched to a biosimilar had to receive doses on an average of 40% higher than those who stayed on the original biologic drug (Minutolo et al. 2017).
Unsurprisingly, patients generally prefer personalized treatment and oppose mandatory switching. Canadian researchers surveyed patients with gastrointestinal diseases, and their caregivers, to ascertain their views on the use of biologic and biosimilar drugs. Of the patients surveyed, 95% said they thought it was important that the decision on the right choice of medication be determined solely by their treating physician in collaboration with them (Attara et al. 2016).
Are Pharmaceutical Expenses Out of Control?
In the field of pharmaceuticals, decision makers implementing public policy must strive to find an ideal balance between encouraging innovation and rapid access to new cutting-edge medications and ensuring the financial viability of drug insurance plans. According to some sources, this delicate balance is about to be broken as increasing availability of the more expensive biologic drugs is compromising the ability of insurance plans to meet the associated increase in costs (Lon?ar et al. 2020: 4). But is this indeed the case?
Despite the increasing availability of biologic drugs in Canada, the growth in total pharmaceutical spending has actually slowed over the past several years. Taking inflation into account, real per capita drug expenditures have grown at an average annual rate of just 0.2% in Canada since 2015, and have actually declined by 0.4% in Quebec (Canadian Institute of Health Information [CIHI] 2019). In addition, the share of gross domestic product (GDP) devoted to prescription drug spending is also declining in Canada, having gone from 1.7% in 2010 to 1.5% in 2019 (CIHI 2019). Even in Quebec, where prescription drug spending had surpassed that of the rest of Canada for the past 20 years, these expenditures represented a smaller share of provincial GDP in 2019 (1.9%) than in 2010 (2.2%) (CIHI 2019).
Ultimately, the advent of biosimilars can be seen as good news for patients and physicians when it increases the range of treatment options available to them, and encourages healthy competition between manufacturers. Where reference biologics and biosimilars are allowed to co-exist without favouring one to the detriment of the other, price reductions are observed for all products (San-Juan-Rodriguez et al. 2019). Negotiating agreements with manufacturers is also a good way to generate savings for governments without restricting choice for doctors and patients. However, government policies that force biosimilar switching for non-medical and strictly economic reasons may ultimately undermine competition, increase total healthcare costs and act as a barrier to innovation and future access of new biologic drugs for all Canadians.
About the Author(s)
Yanick Labrie, MSc, is a health economist and public policy consultant. He is also an affiliated scholar of the Canadian Health Policy Institute and a senior fellow of the Fraser Institute. The views expressed in this article do not necessarily reflect those of these organizations.
Attara, G., R. Bailey, B. Bressler, J. Marshall, R. Panaccione and G. Aumais. 2016. P433. Canadian Patient and Caregiver Perspectives on Subsequent Entry Biologics/Biosimilars for Inflammatory Bowel Disease. Journal of Crohn’s and Colitis 10(supp.1): S319. doi: 10.1093/ecco-jcc/jjw019.552.
Canadian Institute for Health Information (CIHI). National Health Expenditure Trends, 1975 to 2019. Retrieved November 11, 2020 <https://www.cihi.ca/sites/default/files/document/nhex-trends-narrative-report-2019-en-web.pdf>.
Glintborg, B., R. Ibsen, R.E.Q. Bilbo, M.L. Hetland and J. Kjellberg. 2019. Does a Mandatory Non-Medical Switch from Originator to Biosimilar Etanercept Lead to Increase in Healthcare Use and Costs? A Danish Register-Based Study of Patients with Inflammatory Arthritis. RMD Open 5: e001016. doi: 10.1136/rmdopen-2019-001016.
Glintborg, B., J. SØrensen and M.L. Hetland. 2018. Does a Mandatory Non-Medical Switch from Originator to Biosimilar Infliximab Lead to Increased Use of Outpatient Healthcare Resources? A Register-Based Study in Patients with Inflammatory Arthritis. RMD Open 4(2): e000710. doi: 10.1136/rmdopen-2018-000710.
Grant, K. 2019, May 27. B.C. to Become First Province to Force Patients to Switch from Biologics to Less Expensive Biosimilar Drugs. The Globe and Mail. Retrieved November 11, 2020. <https://www.theglobeandmail.com/canada/article-british-columbia-to-be-first-province-forcing-patients-to-switch-from/>.
Institut national d’excellence en santé et services sociaux (INESSS). 2020, June. State of Knowledge: Safety of Switching Biologics and Their Interchangeability. Retrieved November 11, 2020 <https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/Medicaments/CoupDoeil_switching_biologics_EN.pdf>.
Jeremias, S. 2020, June 15. Rising Costs Explain Why Canada is Switching to Biosimilars. The Center for Biosimilars. Retrieved November 11, 2020. <https://www.centerforbiosimilars.com/view/rising-costs-explain-why-canada-is-switching-to-biosimilars>.
Lon?ar, M., L. de Léséleuc and T. Ahuja. 2020, January. Utilization of Innovator Biologics and Biosimilars for Chronic Inflammatory Diseases in Canada: A Provincial Perspective. CADTH Technology Review: Optimal Use 360 Report. Retrieved November 11, 2020. <https://cadth.ca/sites/default/files/ou-tr/ho0007-biosimilars-utilization-final.pdf>.
Minutolo, R., P. Bolasco, P. Chiodini, S. Sposini, M. Borzumati, C. Abaterusso et al. 2017. Effectiveness of Switch to Erythropoiesis-Stimulating Agent (ESA) Biosimilars versus Maintenance of ESA Originators in the Real-Life Setting: Matched-Control Study in Hemodialysis Patients. Clinical Drug Investigation 37: 965–73. doi: 10.1007/s40261-017-0562-8.
Parliamentary Budget Officer (PBO). 2019, April 2. The Impact of the Canada – United States – Mexico Agreement on Prescription Drug Expenditures in Canada. Retrieved November 11, 2020. <https://www.pbo-dpb.gc.ca/web/default/files/Documents/Reports/2019/CUSMA/CUSMA_prescription_drug_expenditures_Canada_EN.pdf>.
Reilly, M.S. and P.J. Schneider. 2020. Policy Recommendations for a Sustainable Biosimilars Market: Lessons rom Europe. Generics and Biosimilars Initiative Journal 9(2):76–83. doi: 10.5639/gabij.2020.0902.013.
San-Juan-Rodriguez, A., W.F. Gellad, C.B. Good and I. Hernandez. 2019. Trends in List Prices, Net Prices, and Discounts for Originator Biologics Facing Biosimilar Competition. JAMA Network Open 2(12): e1917379. doi: 10.1001/jamanetworkopen.2019.17379.
Be the first to comment on this!
Personal Subscriber? Sign In
Note: Please enter a display name. Your email address will not be publically displayed