P3245 - Longer Sustained Remission in Crohn’s Disease With Guselkumab versus Ustekinumab Treatment: Projections From a Disease Model

Mariya Dimova, ¹, Mi Jun Keng, PhD², Feng Pan, PhD³, Dominik Naessens, PharmD, MBA⁴, Leonardo Salese, MD⁵, Zijiang Yang, PhD⁵, Sumesh Kachroo, PhD⁶, Mario A. Gomez Camacho, MD, PhD, MSc, MBA⁷, Myrlene Sanon, MPH⁸
1Janssen-Cilag, Issy-les-Moulineaux, Centre, France; 2Johnson & Johnson, Beerse, Antwerpen, Belgium; 3Johnson & Johnson, Raritan, NJ; 4Janssen Pharmaceutica N.V., Beerse, Brussels Hoofdstedelijk Gewest, Belgium; 5Johnson & Johnson, Spring House, PA; 6Johnson & Johnson, Horsham, PA; 7Johnson & Johnson, Philadelphia, PA; 8Johnson & Johnson, Metuchen, NJ

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 200mg, and 47.9% (p=0.009) for guselkumab 100mg 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 three 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 two was 56.6% versus 49.7%, year three was 47.2% versus 37.9%, and year five was 32.9% versus 22.7% (Figure). 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 versus 36% on ustekinumab (Table).

Discussion: 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 versus ustekinumab.


Figure: Figure. Predicted proportion of patients in clinical remission over 5 years


Figure: Table: Predicted proportion of patients maintaining clinical remission over 5 years, among those who achieved clinical remission in year 1

Disclosures:
Mariya Dimova: Johnson & Johnson – Employee.
Mi Jun Keng: Johnson & Johnson – Employee, Stock Options.
Feng Pan: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).
Dominik Naessens: Janssen Pharmaceutica N.V., – Employee.
Leonardo Salese: Johnson & Johnson – Employee.
Zijiang Yang: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).
Sumesh Kachroo: Johnson & Johnson – Employee, Stock Options.
Mario Gomez Camacho: AstraZeneca – Employee. J&J Innovative Medicine – Employee, Stock Options.
Myrlene Sanon: Johnson & Johnson – Employee.

Mariya Dimova, ¹, Mi Jun Keng, PhD², Feng Pan, PhD³, Dominik Naessens, PharmD, MBA⁴, Leonardo Salese, MD⁵, Zijiang Yang, PhD⁵, Sumesh Kachroo, PhD⁶, Mario A. Gomez Camacho, MD, PhD, MSc, MBA⁷, Myrlene Sanon, MPH⁸. P3245 - Longer Sustained Remission in Crohn’s Disease With Guselkumab versus Ustekinumab Treatment: Projections From a Disease Model, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.