P1658 - Comparative Efficacy of TNF Antagonists and Ustekinumab in Post-Operative Crohn’s Disease

Waseem Ahmed, MD¹, Prerna Mahtani, MS², Yushan Pan, BA³, Anjana Rajan, BA⁴, Daniel Lai, BS³, Benjamin L. Gordon, MD⁴, Emily S. Smith, MD⁴, Randy Longman, MD, PhD², Dana J. Lukin, MD, PhD², Ellen Scherl, MD², Robert Battat, MD^2
1Weill Cornell Medical College, Denver, CO; ²Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medical College, New York, NY; ³Weill Cornell Medical College, New York, NY; ⁴Weill Cornell Medicine, New York, NY

Introduction: Limited data exist on ustekinumab (UST) and vedolizumab (VDZ) in post-operative Crohn’s disease (POCD). No data exist on their efficacy in Tumor Necrosis Factor antagonist (anti-TNF)-exposed POCD patients. Comparative POCD efficacy data are also lacking, hindering guidance on POCD medication selection. We compared the therapeutic efficacies of biologics in POCD patients.

Methods: POCD patients receiving their first post-operative biologic were included (Weill Cornell Medicine biobanks). Demographics, biomarkers, and clinical and endoscopic scores were prospectively collected. For missing data, chart review was performed. The primary outcome compared rates of deep remission (DR, defined as both clinical (HBI< 5, CD-PRO2< 8, or remission stated) and objective (endoscopic (SES-CD< 3, Rutgeert’s<i2a, or absence of ulcers) or biochemical (FCP< 150 µg/g or CRP< 1mg/dL) remission if endoscopy unavailable) between anti-TNF and UST at <12 months post-treatment. Analyses were repeated by indication (prophylaxis or treatment of recurrence) and in TNF-exposed patients. Multivariable logistic regression analyzed factors (IMM, steroid, prior anti-TNF, antibiotic, POCD risk factor, current biologic) associated with DR.

Results: A total of 186 patients (TNF:101, UST:67, VDZ:18) were included (Table 1). DR was higher with POCD anti-TNF treatment compared to UST (45% vs 22%, p< 0.01). Conclusions were identical in those with prior TNF exposure (TNF: 44% vs UST: 19%, p=0.02). Objective (72% vs 53%, p=0.03) and clinical (63% vs 43%, p = 0.03) remission were higher with anti-TNF compared to UST. Conclusions were similar for individual TNF antagonists and compared to VDZ (DR: 12%, p< 0.001). On multivariable analysis, only current anti-TNF use was associated with deep remission (OR 4.0, 95% CI 1.7-9.6).

In patients receiving biologics to treat recurrence, higher rates of DR (44% vs 16%, p=0.008) and objective remission (71% vs 42%, p=0.01) were achieved with anti-TNF compared to UST. In patients receiving prophylactic biologics, DR (TNF:47% vs UST:35%, p=0.4) and objective remission (30% vs. 30%, p=1.0) were similar between groups (Figure 1).

Discussion: In the largest study on UST in POCD, in patients receiving their first POCD biologic, TNF antagonists were associated with improved outcomes compared to UST. Differing efficacies in treating post-operative recurrence existed, whereas prophylactic POCD efficacy was similar between biologics.


Figure: Figure 1: Comparative Efficacy of TNF Antagonists and Ustekinumab in Post-Operative Crohn’s Disease A. All Patients B. Prophylaxis C. Treatment of Recurrence. TNF Antagonists: Green. Ustekinumab: Purple.

	All Patients (186)	# Reported Patients	TNF-Antagonist (101)	# Reported Patients	Ustekinumab (67)	# Reported Patients	Vedolizumab (18)	# Reported Patients
Patient Characteristic
AgeMean (SD) Years	44.5 (± 16.3)	186	43 (±15.5)	101	46.9 (± 16.6)	67	43.9 (± 19.5)	18
Male Gender (%)	44%	186	45%	101	42%	67	50%	18
#Prior BiologicsMedian (IQR25 – IQR75)	1 (0-2)	185	0 (0-1)	100	2 (1-2)	67	1.5 (0-2)	18
Prior Anti-TNF Exposure (%)	64%	119/185	55%	55/100	79%	53/67	61%	11/18
Penetrating Disease (%)	36%	67/185	35%	35/101	42%	28/67	24%	4/17
Prior Surgery (%)	34%	62/183	32%	32/100	34%	22/65	44%	8/18
Active Smoker (%)	6%	12/186	6%	6/101	7%	5/67	6%	1/18
>1 High Risk Factor for Recurrence (%)	59%	110/186	58%	59/101	60%	40/67	61%	11/18
Indication For Therapy
Prophylaxis	37%	69/186	44%	44/101	28%	19/67	22%	4/18
Time of Initiation of Biologic Subsequent to Surgery (Months)Mean(SD)	1.5 (±1.4)		1.6 (±0.2)		1.4 (±1.2)		1.4 (±0.6)
Time to Endpoint Assessment Subsequent to Surgery (Months) Mean (SD)	8.4 (±3.6)		8.2 (±3.8)		9.1 (±2.8)		6.1 (±3.5)
Treatment of Recurrence	63%	117/186	56%	57/101	72%	48/67	78%	14/18
Time of Initiation of Biologic Post-operatively (Months) Mean (SD)	67.7(±82.4)		56.5 (±83.3)		71.2 (±81.3)		106.8 (±104.4)
Time to Endpoint Assessment Subsequent to Initiation of Biologic (Months) Mean (SD)	8.3 (±3.2)		8.4 (±3.0)		7.9 (±3.2)		9.0 (±3.6)
Biologic within 3 years of Surgery (%)	53%	47/89	66%	25/38	44%	17/39	42%	5/12
Concurrent Meds
Immunomodulators	22%	40/186	24%	24/101	19%	13/67	17%	3/18
Antibiotics	17%	25/143	14%	11/78	19%	10/54	36%	4/11
Steroids	17%	32/186	12%	12/101	21%	14/67	33%	6/18

Table: Table 1: Baseline Characteristics Patients on Post-Operative Biologics
SD: Standard Deviation. IQR: Interquartile Range. High Risk Factor: Penetrating Disease, Prior Surgery, Active Smoker.


Disclosures:
Waseem Ahmed indicated no relevant financial relationships.
Prerna Mahtani indicated no relevant financial relationships.
Yushan Pan indicated no relevant financial relationships.
Anjana Rajan indicated no relevant financial relationships.
Daniel Lai indicated no relevant financial relationships.
Benjamin Gordon indicated no relevant financial relationships.
Emily Smith indicated no relevant financial relationships.
Randy Longman: BMS – Advisory Committee/Board Member. Pfizer – Consultant.
Dana Lukin: Abbvie – Consultant, Grant/Research Support. Janssen – Grant/Research Support. Takeda – Grant/Research Support.
Ellen Scherl: AbbVie – Advisory Committee/Board Member, Grant/Research Support. Janssen – Advisory Committee/Board Member, Grant/Research Support. Takeda – Advisory Committee/Board Member.
Robert Battat indicated no relevant financial relationships.


Waseem Ahmed, MD¹, Prerna Mahtani, MS², Yushan Pan, BA³, Anjana Rajan, BA⁴, Daniel Lai, BS³, Benjamin L. Gordon, MD⁴, Emily S. Smith, MD⁴, Randy Longman, MD, PhD², Dana J. Lukin, MD, PhD², Ellen Scherl, MD², Robert Battat, MD². P1658 - Comparative Efficacy of TNF Antagonists and Ustekinumab in Post-Operative Crohn’s Disease, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.