P1023 - Real-World Drug Persistence and Clinical Effectiveness of Ustekinumab After Dual Anti-TNF Failure in Crohn’s Disease

Carl Samaha, MD¹, Logan Slade, PA¹, Jeffrey M. Dueker, MD, MPH¹, Elyse Johnston, MD¹, David Binion, MD², Marc Schwartz, MD¹, Richard Duerr, MD¹
1University of Pittsburgh, Pittsburgh, PA; 2University of Pittsburgh Medical Center, Pittsburgh, PA

Introduction: Patients with Crohn’s Disease (CD) frequently cycle through biologic therapies despite initial response. Clinical trials and real-world studies have demonstrated the efficacy of Ustekinumab (UST), an IL-12/23 inhibitor, as second-line therapy after trial of an anti-TNF. However, real-world data remain limited in its long-term use after dual anti-TNF failure. This study evaluated the persistence and clinical effectiveness of UST in an anti-TNF refractory CD cohort.

Methods: We retrospectively analyzed a cohort of anti-TNF refractory patients with CD enrolled in the SPARC-IBD study. Anti-TNF failure was defined as primary non-response, loss of response, or intolerance due to delayed side effects. We identified 30 patients who initiated UST between 2018 and 2023 following documented failure of ≥2 anti-TNF agents and retrieved their baseline demographics, disease phenotype, and prior medical and surgical history. The primary outcome was UST persistence evaluated by Kaplan-Meier survival analysis. The secondary outcomes were clinical and endoscopic remission measured by sCDAI and SES-CD.

Results: The cohort was majority female (70%) with a median age of 40.5. Most patients had stricturing/fistulizing disease (73%); perianal disease (50%), upper GI involvement (40%), and a history of ileocecal resection (77%) were prevalent. Nearly all had received infliximab (IFX) and adalimumab (ADA) prior to initiating UST. Discontinuation of anti-TNF was due to primary nonresponse (35%), loss of response (27%), and intolerance – infusion/injection reactions (16%), lupus-like syndromes (13%) or psoriasiform rashes (10%). Ten patients (33.3%) discontinued UST during follow-up. The median drug persistence was 2304 days (~6.3 years). At 12 months, over 90% of patients remained on treatment compared to 70% at 3 years and only 43% at 6 years (Figure 1). Among patients still receiving UST at last follow-up (n=20), 70% were in clinical remission and 79% in endoscopic remission, compared to 20% and 21% with mild activity, and 10% with moderate clinical activity.

Discussion: In this real-world cohort of patients with CD refractory to anti-TNF therapy, UST demonstrated high persistence and efficacy through 1 and 3 years. However, more than half of patients ultimately discontinued therapy by six years, reflecting on the challenge of maintaining long-term biologics use in refractory disease. These finding highlight the clinical value of UST after anti-TNF therapy and the need for optimized maintenance strategies.


Figure: Figure 1: Kaplan-Meir Curve of Ustekinumab Survival after Dual Anti-TNF Failure

Disclosures:
Carl Samaha indicated no relevant financial relationships.
Logan Slade indicated no relevant financial relationships.
Jeffrey Dueker indicated no relevant financial relationships.
Elyse Johnston indicated no relevant financial relationships.
David Binion: Blueprint Medicines – Grant/Research Support. Mirador Therapeutics – Grant/Research Support. Takeda – Grant/Research Support.
Marc Schwartz indicated no relevant financial relationships.
Richard Duerr indicated no relevant financial relationships.

Carl Samaha, MD¹, Logan Slade, PA¹, Jeffrey M. Dueker, MD, MPH¹, Elyse Johnston, MD¹, David Binion, MD², Marc Schwartz, MD¹, Richard Duerr, MD¹. P1023 - Real-World Drug Persistence and Clinical Effectiveness of Ustekinumab After Dual Anti-TNF Failure in Crohn’s Disease, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.