Our study demonstrated that the availability of adalimumab biosimilars is associated with reduced adalimumab expenditure while maintaining or increasing adalimumab consumption. This finding is supported by our descriptive and regression analysis conducted across 14 countries, including six countries where adalimumab biosimilars were available.
Our findings suggested that countries with adalimumab biosimilars may achieve financial savings due to two factors. First, the availability of adalimumab biosimilars is associated with lower prices for adalimumab. Although the exact ex-factory prices of both the originator and biosimilar adalimumab were not disclosed due to confidential negotiations between hospitals and pharmaceutical companies, we observed a significant decrease in adalimumab prices among countries where adalimumab biosimilars were available, in comparison to countries where adalimumab biosimilars were not available. Second, the drug-mix effect played a role in reducing adalimumab expenditure, by substituting expensive adalimumab with cheaper alternatives. In previous studies, it has been reported that countries that implement supply-side policies aggressively, like Austria, tend to experience significant price reductions [
41,
75], whereas countries that actively adopt demand-side policies, like Germany, are likely to achieve higher penetration of biosimilars and realize greater budget savings [
24,
38,
76‐
79]. Our results were consistent with those previous studies; namely, we observed that Austria achieved the highest price reduction of 60%, while in Germany, the drug-mix effect was the highest (0.81), indicating a significant shift to cheaper alternatives.
In summary, we found that the presence of biosimilars is associated with reduced expenditure, which is consistent with what has been reported previously [
25,
28,
29,
36,
80]. Of particular significance is the drug-mix effect, which emerged as a major contributor to the observed changes in drug expenditure following the introduction of biosimilars, which is consistent with previous studies [
42‐
46,
81,
82]. Our research underscores the significant advantages of biosimilars, not only in reducing expenditure, but also in improving the availability of vital treatments to patients, demonstrating the substantial value they offer in the evolving healthcare landscape.
Our study has several limitations. First, we focused on only one biologic, adalimumab, and the study period was relatively short. Therefore, the generalizability of our findings to other biosimilars may be limited. While we attempted to include other TNF-α inhibitors (adalimumab, etanercept, and infliximab) that had biosimilars available by 2020, the launch times of etanercept and infliximab biosimilars were closely aligned across jurisdictions, making it challenging to evenly distribute countries with and without biosimilars within the study period. Although Humira
® (adalimumab) is the best-selling biologic in the world as of 2020 [
83], future studies encompassing larger numbers of molecules and longer study periods should be followed. Second, while our analysis encompassed countries with diverse geographic and demographic characteristics, it is important to note that only high-income European nations were included for those with adalimumab biosimilars. As a result, our study primarily emphasized budget savings as the key advantages of biosimilars, omitting other potential benefits of biosimilars. However, previous studies have highlighted access constraints to high-cost medications in middle-income countries [
84,
85]. Therefore, it can be anticipated that the introduction of biosimilars and the consequent price reduction will enhance accessibility in these regions. Future research is needed to generalize our results to other UMIE countries. Third, we estimated the adalimumab consumption of each country by dividing the adalimumab sales volume by the population, rather than using the actual number of patients. This assumption was made due to the challenges of accurately estimating the exact number of patients receiving adalimumab, which has various indications, such as RA, skin diseases, and gastrointestinal diseases. Therefore, we relied on the population as a proxy for the number of patients. Despite its limitations, using population as a denominator allows for relative comparisons of adalimumab consumption between countries. In addition, previous cross-country comparison studies also divided quantity of pharmaceuticals by the population [
50,
61]. Fourth, while the MIDAS-IQVIA data provided insights into utilization patterns across countries based on collected sales volume, there are inherent limitations regarding cost data, especially for hospital products with confidential discounts. Thus, we could not confirm the exact ex-factory prices of adalimumab, which is a clear limitation. However, a previous study showed that the list price of Humira
® decreased after loss of exclusivity, which occurred with the entry of the biosimilars in all included countries in this study except Germany (price unchanged) and France (not included in the study), with −80% in Italy (in the Veneto region, list and ex-factory prices have been unchanged, but discounts have been reported in Italy), − 51% in Austria, − 42% in Spain, and − 37% in Sweden, respectively [
30]. The list price of biosimilar adalimumab was reported to be significantly lower than that of the originator in all included countries, excluding Sweden (the list price of biosimilar adalimumab was not reported) and France (not included in the study), with − 88% in Italy (in the Veneto region), − 58% in Austria, − 42% in Spain, and − 40% in Germany, respectively [
30]. Additionally, the price of the originator significantly decreased, by 89% in the Netherlands and by 80% in the EU tender market, to stave off the use of biosimilars [
34,
35]. Biosimilar competition has also led to considerable price reductions in Denmark, England, and southern European countries, such as in Italy, Portugal, and Spain [
31‐
33]. The more price reductions, the greater the potential cost savings. Moreover, it is worth noting that tenders are conducted in all included countries where adalimumab biosimilars were launched [
39], so the cheapest adalimumab option is the most likely to be prescribed as the winner of the tender. This further supports the speculation that the lower price of adalimumab, coupled with the drug-mix effect resulting from adoption of cheaper biosimilars, is associated with the savings in adalimumab expenditure. Last, our study used the ex-factory prices calculated by dividing the expenditure of adalimumab (in USD) by the quantity of adalimumab (in SU) based on the MIDAS-IQVIA database. Therefore, the actual price reductions for adalimumab may be greater than the price reductions demonstrated in our study.
Despite the limitations mentioned, our study is the first to attempt to assess the changes in expenditure and consumption of a biologic (adalimumab) by comparing 14 countries based on the availability of adalimumab biosimilars, using a regression analysis and decomposing factors associated with adalimumab expenditure. This study highlights the need for biosimilars leading to budget savings and the importance of balancing demand-side and supply-side policies to promote biosimilars use and to achieve sustainable budget savings.