Authors' objectives: Background: In Switzerland, relatively low biosimilar prescription rates have prompted the interest of the authorities. A health technology assessment (HTA) was requested to compare the available evidence of the infliximab reference product and its biosimilar for treating rheumatoid arthritis (RA). Objective: This HTA examines the efficacy, effectiveness and safety of the infliximab biosimilar compared to its reference product in RA and presents the health economic impact of a potentially increased biosimilar utilization in Switzerland. Furthermore, ethical, legal, social and organisational aspects of treatment initiation with biosimilars or switching to biosimilars are analysed. Research questions: Is it safe, efficacious and effective 1) to initiate treatment with infliximab biosimilar instead of the infliximab reference product, 2) to switch treatment from the infliximab reference product to infliximab biosimilar and 3) to switch treatment from infliximab biosimilar to the infliximab reference product in patients with RA?

Authors' results and conclusions: Results: We identified five randomized controlled trials (RCTs) which reported their results in nine publications, 17 real-world evidence (RWE) studies and 13 health economic studies. All included RCTs showed similar clinical efficacy and safety after treatment initiation with biosimilar compared to its reference product. The performed meta-analysis confirmed that there is no difference in efficacy and safety outcomes between treatment initiation with biosimilar and reference product. The certainty of evidence for the critical and important outcomes was judged as moderate to high. Two studies analysed switching from reference product to biosimilar compared to the continuation of reference product treatment. Both studies found comparable efficacy and safety outcomes (i.e. similar number and severity of adverse events) between the analysed groups. Their certainty of evidence was judged as low to moderate. None of the identified studies reported on switching from biosimilar to the reference product. A de novo cost-minimisation analysis showed that treatment initiation with infliximab reference product costs CHF 18’065 more per RA patient than treatment initiation with infliximab biosimilars over a lifetime time horizon. This cost difference is solely based on differences in drug costs. When considering uncertainty behind different model parameters, the difference in drug costs over a lifetime ranged between CHF 10’380 and CHF 23’342 per patient. The budget impact analysis assumed policy scenarios in which the price of the infliximab reference product would be decreased or the use of biosimilars promoted. Cost savings were estimated at CHF 1.58 million over 5 years for approximately 60 annual incident RA patients eligible for infliximab with a range between CHF 0.58 million and 4.78 million. Staying on the infliximab reference product costs CHF 17’812 more per patient than switching to the infliximab biosimilars over a lifetime time horizon (range: CHF 10’126 to CHF 23’088). This cost difference includes differences in drug costs as well as additional physician time and lab tests that may be required related to the switch. In the budget impact analysis savings related to switching to the biosimilar amounted to CHF 9.32 million over 5 years based on approximately 1’000 prevalent RA patients currently treated with the infliximab reference product. When considering uncertainty behind the eligible patient population and future treatment mix the budget impact ranged from CHF 2.20 million to CHF 17.30 million. There were no severe nor highly controversial ethical issues identified based on the scientific evidence concerning treatment initiation with infliximab reference product vs. infliximab biosimilars or when switching from the reference product to biosimilars of infliximab in patients with RA. From a legal perspective, interchangeability of biologics is a key issue. Interchangeability of biologics in Switzerland is not explicitly regulated by neither the therapeutic products law nor the health insurance law. Currently, the decision about interchangeability in an individual case rests with treating physicians in compliance with their professional duties and due diligence. No evidence on social issues associated with the use of biosimilars were identified. Organisational issues may relate to policies to (not) promote and (not) implement biosimilars nationwide. Within this context, relevant are the profit margins that depend on the price of a product. As reference products have higher prices compared to biosimilars, there are financial incentives to use reference products instead of biosimilars. Conclusion: Treatment initiation with infliximab biosimilar or switching to infliximab biosimilar showed comparable efficacy, effectiveness and safety compared to treatment initiation with the reference product or to continuation of reference product in patients with RA, respectively. The certainty of evidence for treatment initiation was judged moderate to high whereas for treatment switch it was low to moderate. Potential policy interventions reducing the price of the infliximab reference product or promoting the use of biosimilars could lead to cost savings of CHF 1.6 million for treatment initiation based on approximately 60 annual incident RA patients and CHF 9.3 million for treatment switch based on approximately 1’000 prevalent RA patients over five years.

Authors' methods: Methods: A systematic literature search for evidence on efficacy, effectiveness, safety and health economic outcomes of the infliximab reference product compared to biosimilars in RA was conducted. Meta-analysis was performed for outcomes with sufficient available evidence. The certainty of evidence for relevant outcomes was assessed by applying the GRADE approach. A de novo health economic model was built to assess cost differences between a RA patient treated with infliximab reference product and a patient treated with its biosimilar using a lifetime time horizon. The potential budget impact for Switzerland was estimated over the next five years. The health economic analysis focused on drug costs. Additional physician time and lab tests that may be required related to the switch were also considered. Furthermore, a targeted search for evidence on biosimilar-related ethical, legal, social and organisational aspects was conducted and findings were summarized and discussed.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/infliximab.html

Year Published: 2021

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0047infx-hta-report.pdf.download.pdf/h0047infx-hta-report.pdf

URL for additional information: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-programm.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health