Comparative Cost-Effectiveness of Advanced Treatment Sequences for Moderately to Severely Active Ulcerative Colitis in Japan.

INTRODUCTION: Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease characterized by a relapsing course, substantial symptom burden, and long-term healthcare utilization. Although multiple advanced therapies (ATs) are available for patients with moderately to severely active UC, evidence to guide optimal treatment sequencing remains limited, particularly in Japan. This study evaluated the cost-effectiveness of clinically relevant AT sequences for moderately to severely active UC in Japan. METHODS: A hybrid decision-tree and Markov model was developed to compare AT sequences over a lifetime horizon from the payer perspective. The model captured both induction and maintenance phases for each therapy. Efficacy and safety inputs were derived from a previously published Bayesian network meta-analysis and supplemented with Japan-specific clinical and economic data. Costs and quality-adjusted life years (QALYs) were discounted at an annual rate of 2.0%. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness was assessed against a Japanese cost-effectiveness threshold of JPY 7,500,000 per QALY (USD 49,547 per QALY). RESULTS: A total of 79 treatment sequences were evaluated. First-line etrasimod followed by second-line upadacitinib yielded the greatest health benefit (17.801 QALYs). Four treatment sequences-infliximab followed by ustekinumab, infliximab followed by etrasimod, infliximab followed by upadacitinib, and etrasimod followed by upadacitinib-were located on the efficiency frontier. Compared with infliximab-ustekinumab, infliximab-etrasimod resulted in an ICER of JPY 1,095,181 (USD 7235) per QALY. In turn, infliximab-upadacitinib had an ICER of JPY 1,218,896 (USD 8052) per QALY compared with infliximab-etrasimod. Etrasimod-upadacitinib had an ICER of JPY 6,684,442 (USD 44,160) per QALY compared with infliximab-upadacitinib. All ICERs were below the Japanese cost-effectiveness threshold. CONCLUSION: Under the assumptions of this model, a treatment sequence with first-line etrasimod followed by second-line upadacitinib was identified as the most cost-effective strategy for advanced therapy-naïve patients with moderately to severely active UC in Japan.