Evaluating the benefits of TNF-alfa inhibitor biosimilar competition on off-patent and on-patent drug markets: A Southern European analysis

Background: The level of competition achieved following biosimilars market availability varies by country, care setting and molecule. Hence, biosimilars contribution to attaining price reductions and extended access to treatments can also vary. Objective: The aim of this study is to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors and competing molecules in Southern European markets (2011–2020), and to evaluate the benefits of the competition generated by the availability of biosimilars. Methods: This study is based on a literature review examining market characteristics for TNF-alfa inhibitors and competing immunomodulator molecules, and on the quantitative analysis of market data for these molecules in Italy, Portugal and Spain. Results: Following biosimilars availability in Italian, Portuguese and Spanish markets, there has been an expansion in the overall access to TNF-alfa inhibitor pharmaceuticals. Further, savings have been generated within the TNF-alfa inhibitors class even after the increased use of these molecules. However, the potential of infliximab, etanercept and adalimumab biosimilars to generate price competition outside of their own drug class appeared limited in the studied markets. Considering this limitation and that shifts towards on-patent and higher-cost therapies have occurred after TNF-alfa inhibitor biosimilars availability, the importance of investing in biosimilars development for still on-patent immunology biologics is emphasized. Conclusion: This study highlights the need for policies that do not only seek higher utilization of biosimilars, but that also support a sustainable market for these products. This is expected to foster the future development of biosimilar medicines.


Data sources
The following data sources have been consulted to gather consumption volume and NHS expenditure data for TNF-alfa inhibitors and competing immunomodulators.

Italy
We have consulted reports (2011-2021) emitted by the Italian Medicines Agency (AIFA) Medicines Utilization Center (OsMeD) on the yearly use of medicines. These reports are publicly available, either in Italian or English (depending on the year) and provide a national-and regional-level overview on consumption and expenditure data (OsMed, 2001(OsMed, -20222017). Consumption volume data have generally been expressed as defined daily doses (DDD) per 1000 inhabitants per day or as DDD per capita per day. NHS expenditure has been expressed in euros as per capita expenditure.
Data on biosimilar market shares (expressed as a percentage; represent the consumption volume of biosimilar products, over the volume of biosimilars plus the respective originator molecule ) have been published within AIFA reports on the monitorization and consumption of biosimilars (data are available at the regional level since 2019)(AIFA, 2019-2022).

Portugal
The Portuguese National Authority of Medicines and Health Products (Infarmed) publishes monthly reports on the consumption and expenditure associated to high-use/high-cost medicines in the ambulatory and the hospital setting. These reports are publicly available (Infarmed, 2007(Infarmed, -2022. However, data are not reported systematically for every product purchased by the NHS within a therapeutic class. For our analyses, data from the above-mentioned reports were complemented with consumption volume/expenditure data provided by Infarmed (for publicly managed hospitals in the regions Alentejo, Algarve, Centro, Lisboa e Vale do Tejo, Norte) for the molecules: abatacept, adalimumab, anakinra, apremilast, baricitinib, brodalumab, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, tocilizumab, tofacitinib, ustekinumab, vedolizumab. Consumption volume data have been expressed in number of units (defined by the Código Hospitalar Nacional de Medicamentos; tablets, capsules, pens, injectable solutions, etc.). NHS expenditure has been expressed in euros as yearly expenditure for the total number of units purchased by public NHS hospitals. Data on biosimilar market shares (expressed as a percentage; represent the consumption volume of biosimilar products, over the volume of biosimilars plus the respective originator molecule) have been published within the Infarmed website 'Medicamentos biossimilares' (SNS, 2021).

Spain
We contacted the Department of Pharmaceuticals and Health Products within the Spanish Ministry of Health for information about consumption volume and NHS expenditure for TNF-alfa inhibitors and competing immunomodulators. We received data for the molecules: abatacept, adalimumab, anakinra, apremilast, baricitinib, brodalumab, certolizumab pegol, etanercept, filgotinib, golimumab, guselkumab, infliximab, ixekizumab, risankizumab, rituximab, sarilumab, tildrakizumab, tocilizumab, tofacitinib, upadacitinib, ustekinumab, vedolizumab. Consumption volume data have been expressed in DDD per 1000 inhabitants per day. NHS expenditure has been expressed in euros as yearly expenditure for the total number of units purchased by public NHS hospitals. The ex-factory price has been discounted according to the specifications of the Decree Law 9/2010, 20 th May (RDL 9/2010, 20 mayo) (BOE, 2010).
Data on biosimilar market shares (expressed as a percentage; represent the consumption volume of biosimilar products, over the volume of biosimilars plus the respective originator product) have been provided upon request by the Spanish Ministry of Health, Department of Pharmaceuticals and Health Products (national-level data) and the Spanish Association of Biosimilar Medicines (BioSim; national and regional-level data ) 4.