Original Title: État des connaissances: innocuité de la substitution et de l’interchangeabilité des médicaments biologiques

Authors' objectives: In Québec, despite the fact that the Ministère de la Santé et des Services sociaux (MSSS) established, in 2017, restrictive rules promoting the expansion of the biosimilar market, their use remains low. If biosimilars are not used optimally, the significant increase in the use of biologics could create an untenable financial strain on public drug insurance plans, which could greatly compromise access to innovative therapies. The MSSS therefore asked the Institut national d'excellence en santé et en services sociaux (INESSS) to produce a state-of-knowledge report on the risks associated with switching biologics and their interchangeability. This report will be incorporated into the national action plan under the MSSS’s responsibility. For the purposes of the MSSS's request, INESSS used an approach based on scientific data and the perspectives of Québec clinicians. The purpose of this report is to provide scientific data on the efficacy and safety of switching biologics, the features of policies put in place in other countries and Canadian provinces, guidance documents from learned societies, and the perspectives of Québec clinicians and pharmacists.

Authors' results and conclusions: RESULTS-(SWITCHING SAFETY:) The immunogenicity of a biologic can vary according to the patient’s characteristics, the molecule used, and the disease being treated. However, the loss of a biologic’s efficacy over time is not solely due to immunogenicity. It can also be caused by a natural disease progression or by a more rapid drug elimination. The systematic literature reviews carried out in this report to assess the safety of switching between biologics did not reveal a statistically significant difference, in terms of loss of therapeutic efficacy, immunogenicity, retention rate, and adverse events between patients whose treatment was switched and those who remained on the reference biologic. The levels of evidence associated with these outcomes were considered moderate overall for inflammatory arthritis, diabetes, anemia, and plaque psoriasis. However, the levels of evidence were considered low for loss of therapeutic efficacy in inflammatory bowel disease and insufficient in oncology and for multiple switches. (FEATURES OF POLICIES): Most jurisdictions favour switching patients treated with a reference biologic drug to a biosimilar but do not impose it for all patients. Only a few European countries and two Canadian provinces have instituted policies that lead to a mandatory non-medical switch for most patients (national tendering process or coverage only for the biosimilar). (POSITIONS AND PERSPECTIVES OF QUÉBEC CLINICIANS): The preferential use of biosimilars in naïve patients and switching to a biosimilar under medical supervision in patients already receiving treatment with a reference biologic are generally accepted by clinicians. Non-medical switching in patients already receiving treatment with a reference biologic is generally not accepted by learned societies and the consulted clinicians. The latter are concerned about, among other things, the destabilization of patients who are complex cases and for whom few treatment options are available. They are also concerned about the absence of mechanisms for preventing such patients from being excluded from a non-medical switch, the fact that it is not possible to switch back in the event of a loss of efficacy or significant adverse events following the switch, and the risks associated with multiple switches. To improve medication monitoring, the consulted clinicians indicated that greater use could be made of anti-drug antibody, neutralizing anti-drug antibody and biologic drug assays. If a non-medical switch policy is implemented in Québec, they stress that the transition should be gradual and be aimed primarily at stable patients with no particular condition. They added that good communication between the MSSS, clinicians and patients will be very important for facilitating the transition. Lastly, they indicated that the savings generated should be used to improve the service to patients and could thus offset the loss of manufacturer-supported assistance programs. CONCLUSIONS: This report identifies certain populations or biologics for which very little or no data are available regarding the safety of biologics switch, and the significant concerns that clinicians have about non-medical switching. Most of the available scientific data have methodological limitations and raise significant uncertainties. Therefore, conducting adequate clinical studies with a larger number of individuals from these populations and greater homogeneity in the participants’ baseline characteristics would be useful for better determining the impact of switching between biologics.

Authors' methods: SCIENTIFIC DATA: To assess the safety of switching biologics, we conducted systematic reviews in several bibliographic databases from 2006 (when the first biosimilars were marketed) to December 2019 to identify all the primary studies and systematic reviews published on the subject. To document the conditions of use and the positions of learned societies, we conducted a systematic literature review to identify guidance documents, clinical practice guidelines (CPGs), position statements and any other items containing recommendations published between January 2013 and December 2019. The grey literature and government websites were consulted to complete the research on the features of policies put in place in other countries and Canadian provinces. Items were selected according to predefined exclusion and inclusion criteria, and the quality of these items was assessed using the appropriate tools. These steps were carried out independently by two reviewers. The data were then extracted by one reviewer and validated by the other. The results are presented in tables and summarized in the form of an analytical narrative synthesis. PROCESS FOR ASSESSING THE QUALITY OF THE SCIENTIFIC EVIDENCE: The main results reported in the selected studies are presented as brief statements of scientific evidence. An overall level of scientific evidence was assigned to each statement according to a four-level scale (high, moderate, low, insufficient). QUÉBEC CLINICIANS' PERSPECTIVES: INESSS formed a panel of experts to obtain the perspectives of Québec clinicians regarding the switch of biologic drugs. The panel brought together 19 health professionals representing the main professional associations concerned by the use of biologics. Among other things, the discussions enabled INESSS to gather clinicians' perspectives on the following general aspects: clinical aspects and social and organizational considerations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/innocuite-de-la-substitution-et-de-linterchangeabilite-des-medicaments-biologiques.html

Year Published: 2020

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/innocuite-de-la-substitution-et-de-linterchangeabilite-des-medicaments-biologiques.html

Requestor: Minister of Health

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec