S1741 Longer Sustained Remission in Crohn’s Disease With Guselkumab vs Ustekinumab Treatment: Projections From a Disease Model

Introduction: Crohn’s disease (CD) is a progressive disease associated with reduced quality of life. Therapeutic goals and clinical guidelines have evolved to include endoscopic outcomes as a key prognostic parameter in disease management (STRIDE II). Guselkumab, a dual-acting IL-23 inhibitor, investigated in double-blind placebo-control, active comparator, Phase 3 trials, demonstrated superiority in 48-week efficacy to ustekinumab in achieving endoscopic response with 52.7% (P < 0.001) for guselkumab 200 mg, and 47.9% (P = 0.009) for guselkumab 100 mg vs 37.1% for ustekinumab. To better understand the implication of endoscopic response on long-term remission, a disease model was developed to compare long-term disease clinical remission status for guselkumab and ustekinumab. Methods: A state-transition model was developed to simulate long-term disease status change for patients with CD who initiate guselkumab or ustekinumab. In the model, patients can be in one of the 3 health states – clinical remission, clinical response without clinical remission, and active CD. For the first 48 weeks, the rates of clinical remission and clinical response are based on the GALAXI Phase 3 trials. After week 48, endoscopic response status based on galaxi 2-year long-term extension data were used to estimate the durability of clinical remission defined as those achieving clinical remission at each year over a 5-year period. Overtime, patients losing clinical remission or response will move to the active CD state. Results: The model predicts the proportion of patients in clinical remission for guselkumab compared to ustekinumab at year 2 was 56.6% vs 49.7%, year 3 was 47.2% vs 37.9%, and year 5 was 32.9% vs 22.7%. The difference in proportion of patients attaining clinical remission with guselkumab compared to ustekinumab increases from 5% at year 1 (68% vs 63%) to 10% at year 5 (33% vs 23%). Model predicts over 5 years, among patients who achieved clinical remission at 1 year, 49% maintained clinical remission on guselkumab vs 36% on ustekinumab. Conclusion: The model projections suggest treatment with guselkumab leads to better long-term outcomes for patients with CD, compared to ustekinumab. The results support the utility of endoscopic response as a predictor of long-term outcomes and suggests longer sustained clinical remission with guselkumab treatment vs ustekinumab.