Brand-name adalimumab (Humira, hereinafter originator) is by far the most cost-intensive pharmaceutical product in the US with global sales of $19.9 billion in 2018. 1 Five adalimumab biosimilars have been approved by the US Food and DrugAdministration, but none are marketed owing to patent disputes. The first to become marketed is expected in January 2023. 2 A 2019 Viewpoint argues that cost savings in the US due to adalimumab biosimilars might vanish as patients might switch to newer and better drugs before the biosimilars become available. 3 The lack of adalimumab biosimilars results in substantial premiums being paid by patients and payers when much cheaper biosimilar drugs are available outside the US.Denmark, a member of the European Union with 5.8 million inhabitants, has benefited from substantial discounts owing to a well-planned implementation of adalimumab biosimilars. In Denmark, adalimumab is provided to patients in public outpatient clinics and bought through national tenders. There is no automated substitution to biosimilars, but the treatment recommendations from the Danish Medicines Council was changed to adalimumab biosimilars for all indications following the patent expiration of the adalimumab originator. This included switching patients to a biosimilar who were already well treated with the originator (nonmedical shift). We present the nationwide shift to adalimumab biosimilars across all indications in Denmark and calculate the actual associated cost reductions.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry.Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures.Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab.Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures.Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Terms of use This work is brought to you by the University of Southern Denmark through the SDU Research Portal. Unless otherwise specified it has been shared according to the terms for self-archiving. If no other license is stated, these terms apply: • You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access version If you believe that this document breaches copyright please contact us providing details and we will investigate your claim.

Purpose The aim of this study was to describe the implementation and uptake of biosimilar trastuzumab in Denmark compared with other European countries. Methods European data for usage of trastuzumab was supplied by IQVIA™, using the MIDAS® dataset. A comparison was performed based on market share estimated in sales volume. A separate comparison was undertaken between countries with a full two-fold switch between different biosimilars. Data was collected spanning the time from first registered sales of biosimilar trastuzumab until the 1st quarter of 2020. Results Denmark had the fastest and most thorough uptake of biosimilar trastuzumab compared with other EU countries. After 3 months, the market share of biosimilar trastuzumab had increased to 90% while the second fastest country had a 50% market share after 3 months. Only two other countries had undergone a full second switch between biosimilars, Hungary and Norway. All of the three countries made near complete switches between biosimilars while only Denmark had reduced the use of biooriginator below 10%. Conclusion The implementation of biosimilar trastuzumab in Denmark was rapid and achieved high overall uptake compared with other EU countries. The switch from one biosimilar to another was also achieved quickly and thoroughly. We believe that the rapid dissemination of information and involvement of all stakeholders — administrators, pharmacies, prescribers, nurses, and patients — constitute the backbone of the Danish success. A similar strategy is recommend for biosimilar implementation in other countries.

BackgroundThe use of expensive biological drugs in rheumatology is rapidly increasing and has led to substantial increases in drug expenditures. A considerable reduction of drug costs is possible by using biosimilars as soon as they become available and carrying out non-medical shifts to biosimilars (i.e. switching a patient well treated on a biooriginator to the biosimilar). Research on biosimilars has focused on interchangeability and safety outcomes, but little focus has been on nationwide implementation and the direct economic consequences on drug expenses.In Denmark, TNF-inhibitors are solely given in an in-hospital setting and bought through national tenders. The Danish in-hospital organization includes Regional Drug and Therapeutics Committees that ensures regional implementation of treatment guidelines and close collaboration between hospital pharmacies and regional clinical pharmacologists. Furthermore, the implementation of TNF-inhibitor biosimilars was preceded by careful preparations from among others a newly established national biosimilar task force.ObjectivesThe aim of this study was to describe the implementation of the two first TNF-inhibitor biosimilars (infliximab and etanercept) in Danish departments of rheumatology.MethodsMonthly data on drug sales to Danish rheumatology departments were used to assess the biosimilar uptake rate and subsequent changes in the drug expenditures during the implementation in Denmark.ResultsShifts to biosimilars were begun within a few months following end of biooriginator patent, vertical lines in the figure. Use of the infliximab biosimilar was begun in April 2015, and in August 2015 biosimilar uptake was 92.9% of total infliximab use. Similarly use of etanercept biosimilar was begun in April 2016, and in June 2016 the biosimilar uptake was 91.6% of total etanercept use. In January 2015 the total use in Defined Daily Doses (DDD) were 42.4 thousand DDD’s for infliximab and 37.3 thousand DDD’s for etanercept. The use increased steadily and was in January 2018 138.4 thousand DDD’s for infliximab and 62.1 thousand DDD’s for etanercept (equivalent to increases of 226.6% and 66.8%). The increases in DDD’s were not reflected in total drug costs due to the shift to biosimilars. The total drug cost for infliximab in January 2015 was 6.7 million DKK but was reduced to 5.4 million DKK in January 2018 (-19.4%). A corresponding cost reduction was seen for etanercept (11.3 million DKK in January 2015, 8.1 million DKK in January 2018, -28.7%).ConclusionDanish departments of rheumatology experienced a fast and near-complete switch of infliximab and etanercept biooriginators to biosimilars. At the same time the use of the drugs increased substantially, but due to large price reductions the total drug cost decreased despite the increasing use. We believe that a thorough preparation and an organizational setting supporting the implementation was crucial for the successful implementation. The Danish structure, with its national tendering, probably contributed to the substantial drug...