Objectives: This study aims to assess the cost-effectiveness and budget impact (BI) of Upadacitinib (UPA) compared to other biologics for treating moderate-to-severe active Crohn's Disease (aCD) in Greece. The assessment considers biologic-naïve patients (CCF) and biologic-experienced patients (BF).

Methods: A cost-effectiveness model (CEM) incorporating a decision tree for the induction period and a 60-year Markov model for the maintenance period was adapted to compare UPA versus Adalimumab (ADA), Ustekinumab (UST), Vedolizumab (VDZ), Infliximab (IFX) in CCF, and versus ADA, UST, and VDZ in BF, from the Greek payer perspective (EOPYY). Induction clinical efficacy data were derived from UPA trials (U-EXCEL, U-EXCEED); maintenance and comparator efficacy data were sourced from a network meta-analysis. Utilities and adverse event rates were obtained from the literature. Local up-to-date direct medical costs were used (EUR, 2023). Health outcomes were measured in quality-adjusted life years (QALY). An incremental and a pairwise analysis (UPA versus UST) resulting to an incremental cost-effectiveness ratio (ICER) were conducted. In the five-year BI model (BIM), epidemiology data from the literature indicated that the total number of patients with moderate-to-severe aCD in Greece would increase from 3,912 (Year 1) to 4,755 (Year 5). Two market scenarios were compared: the current market, where UPA is not reimbursed for aCD in Greece, and the projected market, where UPA's penetration increases from 4% to 8% over five years.

Results: In CCF, UPA was dominated by IFX-biosimilar, whereas, in BF versus UST, it would yield 0.105 additional QALYs and €2,314 additional costs, with an ICER of €22,004/QALY gained. The BIA results showed that introducing and progressively utilising UPA in the moderate-to-severe aCD patients market would increase EOPYY budget by €964,644 over five years.

Conclusions: UPA is a cost-effective treatment option for managing BF patients with moderate-to-severe aCD. Its insignificant budget impact increase would ensure viability within the Greek healthcare system.