Presentation (CTI)

OBJECTIVES: Selective interleukin-23 (IL-23) p19 inhibitors and Janus kinase inhibitors (JAKi) are novel therapeutic options for moderate-to-severe Crohn's disease (CD), but their optimal sequence position and economic value are uncertain. We aimed to evaluate clinical outcomes, costs, and cost-utility of positioning these mechanisms across treatment lines.
METHODS: We developed a lifetime Markov model from the Hong Kong public healthcare perspective for patients with moderate-to-severe CD, with treatment strategies defined at the mechanism-of-action level. The model included induction tunnel states and maintenance states of clinical remission, response, no response, surgery, and death. The reference strategy was tumor necrosis factor (TNF) inhibitors, then non-TNF biologics, then best supportive care. Comparator strategies placed IL-23 inhibitors or JAKi first, second, or third line. Efficacy and safety inputs were synthesized from randomized trials and evidence syntheses, stratified by prior advanced therapy exposure. Costs were derived from public drug prices and Hong Kong Hospital Authority electronic medical records. Outcomes were evaluated using quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).
RESULTS: In the 10-year analysis, IL-23 second-line produced the largest health gain (+0.0917 QALYs) and greatest surgery reduction (-9.1 percentage points); among JAKi strategies, second-line use performed best (+0.0581 QALYs; surgery rate -6.9 percentage points). In lifetime analysis, the reference, JAKi second-line, and IL-23 second-line strategies formed the cost-effectiveness frontier. JAKi second-line and IL-23 second-line gained 0.1600 and 0.2818 QALYs, with ICERs of HK$2,077,332/QALY and HK$4,258,656/QALY, both exceeding 1- and 3-times Hong Kong gross domestic product (GDP) per capita thresholds. Deterministic analyses identified drug prices as the main drivers of ICERs.
CONCLUSIONS: IL-23 inhibitors and JAKi improved predicted long-term clinical outcomes, with second-line use most favorable for both mechanisms. IL-23 second-line offered greater clinical benefit, whereas JAKi second-line had the lower ICER among novel-mechanism strategies. High drug acquisition costs remain the key barrier to cost-effectiveness.