Impact of Regional Healthcare Policy Interventions on Biosimilar Use: A 10-year Evaluation of TNFα Inhibitors Utilization in Italy

Background and objectives: Tumor neurosis factor alpha (TNFα) inhibitors are widely used for the treatment of immune-mediated inflammatory diseases. Following the patent expiration of infliximab, etanercept, and adalimumab, biosimilars have become available in Europe. In Italy specifically, each region adopted heterogeneous strategies to promote biosimilar uptake. The aim of this study was to describe the impact of different regional healthcare policy interventions on the utilization of biosimilars of adalimumab, infliximab, and etanercept in the last decade. Methods: A descriptive, multiregional, retrospective cohort study was conducted in Italy in the period 2015-2023 using claims data of 14 regions from the VALORE distributed database network. First, regional policy interventions related to TNFα inhibitors biosimilars were retrieved from the regional official websites and classified into six categories: monitoring procedures, regional guidelines, regional prescribing recommendations, drug expenditure/prescription quotas, medication supply timing, and financial incentives. Secondly, the proportion of biosimilar users among incident and prevalent users of TNFα inhibitors with expired patent, stratified by active ingredient, calendar year, and region, was calculated. Then, regional policy intensity was quantified for each year using a composite score on the basis of the six categories of healthcare policy, and categorized into three levels (0, 1, ≥ 2). Short-term changes in biosimilar use were assessed as the absolute percentage change between the year of policy adoption (t) and the subsequent year (t + 1), across both policy intensity levels and policy types, and reported as medians, and interquartile ranges. Finally, the compound annual growth rate (CAGR) of the prevalence of TNFα inhibitors biologic users per 100,000 inhabitants over time was calculated to estimate the temporal trend of TNFα inhibitors use in the study period. Results: A total of 88 types of regional policy interventions in the form of official decrees or documents related to biosimilar use were issued by the involved regions. The most common healthcare policies implemented were regional prescribing recommendations and drug expenditure/prescription quotas (n = 27, 30.7%). In the years 2015-2023, a total of 128,288 prevalent users of patent-expired TNFα inhibitors, with 112,526 being incident users, were identified. Overall, prevalent biosimilar users increased from 9% in 2015 to 84% in 2022, with differences across regions. This proportion was almost always above 80% among incident users across the study period, with a more homogeneous uptake between regions. Concerning policy analyses, years in which regions implemented ≥ 2 policy interventions showed greater short-term increases in biosimilar use: 31% for adalimumab, 18% for etanercept, and 14.5% for infliximab, compared with years with no policy implementation (9%, 9%, and 8.5%, respectively). Increases in biosimilar uptake were also detected across policy types for all TNFα inhibitors. The mean CAGR of the prevalence of TNFα inhibitors' biologic use over the study period was +5.7%. Conclusions: Our study observed a steady increase in TNFα inhibitors biosimilar use in Italy over time. However, regional differences in healthcare policy interventions led to unequal biosimilar access and uptake, underscoring the need for more coordinated national strategies. Both the intensity and timing of regional policy interventions appeared to influence biosimilar uptake, regardless of the specific type of policy, with higher intensity, and earlier-adopted policies associated with greater short-term biosimilar uptake. A moderate increase in TNFα inhibitors biologic use over time was observed, possibly supported by the increased uptake of biosimilars.