Rodríguez Lago, IagoPeinado Fabregat, José IgnacioGuigini, Marcelo AlejandroCerezales, MónicaIbáñez, FranciscoCrespo, CarlosBarreiro de Acosta, Manuel2026-06-192026-06-192026-05-01Rodríguez-Lago, I., Peinado-Fabregat, J.I., Guigini, M. et al. Cost-effectiveness analysis of sequential treatment strategies for moderate to severe Crohn’s disease in Spain: where should biosimilar ustekinumab be positioned?. PharmacoEconomics Open 10, 557–566 (2026). https://doi.org/10.1007/s41669-026-00642-12509-426210.1007/s41669-026-00642-1https://hdl.handle.net/20.500.14454/6252Background/Objective Crohn’s disease is associated with a high economic burden for the Spanish National Healthcare System, driven by pharmacological expenses. Following the recent incorporation of ustekinumab biosimilars into the market, this study aimed to evaluate the cost effectiveness of different treatment sequences, including biosimilar ustekinumab (bsUST), for moderate-to-severe Crohn’s disease from the NHS perspective in Spain. Methods Treatment sequences were defined according to clinical practice. A Markov model with 2-week cycles and a lifetime horizon was developed, Including health states such as active disease, response, remission, surgery, and death. Funnel states simulated induction and treatment changes after loss of response, and surgery was considered only after four pharmacological lines. Efficacy data for biosimilar adalimumab (bsADA), biosimilar intravenous infliximab (bsIFX), biosimilar ustekinumab (bsUST) risankizumab (RIS), upadacitinib (UPA), vedolizumab (VDZ), and surgery (Q) were obtained through published literature, including network meta-analyses and clinical trials. Unitary costs were sourced from Spanish databases and literature. Pharmacological costs were ex-factory prices applying Royal Decree-Law (RDL) 8/2010 discount. For bsADA and bsIFX, average biosimilar market prices were used. A 30% discount was assumed for bsUST versus reference ustekinumab. Sequence 1 (bsADA-bsUST-UPA-RIS-Q) was set as the reference. Results Alternative strategies provided QALY gains ranging from 0.06 to 0.34 compared with the reference. However, due to varying incremental costs, Sequence 2 (bsUST, bsADA, UPA, RIS, Q) emerged as the only cost-effective strategy at a willingness-to-pay threshold of €27,000/QALY, with an incremental cost-effectiveness ratio (ICER) of €8672.6/QALY. Conversely, all other sequences exceeded the threshold, with ICERs starting at €42,594/QALY. Probabilistic sensitivity analysis confirmed the robustness of these findings, identifying Sequence 2 as the cost-effective option in 98.03% of simulations. Conclusions Positioning bsUST as a first line of treatment appears to be cost effective and an efficient alternative from the NHS perspective in Spain. Additionally, none of the alternative sequences proved to be cost effective compared with the sequence starting with bsADA-bsUST. bsUST may significantly impact Crohn’s disease management in Spain, improving patient access due to its lower drug acquisition costs.© The Author(s) 2026journal article2026-06-192509-4254