E0342 - Characterization of Crohn’s Patients That Are Multiple Primary Non-Responders to Biologic Therapies

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Justin Field, MD

Icahn School of Medicine at Mount Sinai

Justin Field, MD, Ryan Ungaro, MD, MS, Louis Cohen, MD, Jean-Frederic Colombel, MD
Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Despite the advance in therapeutic options for the treatment of Crohn’s disease (CD), there remains a significant portion of patients with ongoing disease activity. Few studies have characterized medically refractory CD. Identifying patients that are true primary non responders to multiple therapies may reveal novel mechanisms on which future therapies can be built. Here we describe the clinical characteristics of CD patients that are primary non-responders to all 3 FDA approved classes of biologics from a tertiary center.

Methods: Two datasets were used to optimize criteria for primary medical non-responders: a randomly selected cross sectional dataset of 783 patients and a dataset of 42 patients screened for a clinical trial that permitted failure of 3 biologics. Internal review of the datasets and iterative optimization of primary non-response criteria settled on the following factors to define primary medication non-response (1) demonstrated endoscopic disease activity, (2) trial of therapy > 6 months, and (3) no record of adverse event.

Results: Of 806 patients reviewed, 19 met criteria for primary non response across 3 biologic classes. Mean age at diagnosis was 24.7 and 53% were male. Disease distribution: 13 (68%) patients with ileocolitis, 4 (21%) patients with colitis, & 2 (11%) patients with ileitis/jejunitis. 2 (11%) patients had upper tract involvement. Regarding phenotype, 5 (31.2%) patients had inflammatory (B1), 5 (31.2%) had fibrostenotic (B2), & 9 (56.3%) patients had penetrating (B3) disease. 3 (15.7%) patients had perianal disease. 12 (63%) patients had prior CD surgery. The refractory patients had more upper tract disease and B3 disease compared to controls. 18 patients received an anti-TNF agent as the 1st biologic class & 1 received an anti-a4b7 integrin. 2nd class: 10 received anti-a4b7 integrin, 8 received an anti-IL12/23, & 1 received anti-a4b1 integrin. 3rd class: anti-a4b7 integrin in 10, anti-IL12/23 in 8 and anti-TNF in 1. Strategies employed after biologic failure were trial referral (16), recycling class (10), med optimization (5), surgery (2), off label meds (2) & combo biologics (1).

Discussion: This retrospective review demonstrates there is a subset of highly medically refractory CD patients that are primary non-responders to multiple biologics. Common clinical characteristics don’t allow the identification of these patients, suggesting the need for molecular phenotyping in order to identify rational rescue therapies for this unique subset of patients.

Figure: Figure 1: Sequence of class selection in group of multiple biologic refractory patients

	Multiple Biologic Refractory Patients (n = 19)	Non-Refractory Patients (n = 787)	P value
Mean age at Dx (yrs)	24.7	26.17534943	0.999
Male	10 (52.6%)	427 (54.2%)	0.883
Female	9 (47.4%)	360 (45.7%)	0.883
Ileocolitis Distribution	13 (68.4%)	413 (52.4%)	0.278
Colitis Distribution	4 (21.1%)	173 (22.0%)	0.278
leal Distribution	2 (10.5%)	201 (25.5%)	0.278
Upper GI CD	2 (10.5%)	9 (1.14%)	0.0005
B1 (Non-stricturing, Non-penetrating)	5 (26.3%)	455 (57.8%)	---
B2 (Stricturing)	5 (26.3%)	225 (28.6%)	---
B3 (Penetrating)	9 (47.4%)	106 (13.5%)	0.00002
Perianal Disease	3 (15.8%)	69 (8.77%)	0.289
Prior CD Surgery	11 (58.0%)	340 (43.2%)	0.201

Table: Table 1: Comparison of clinical characteristics between refractory group (primary non-response to 3+ classes of biologics) vs non-refractory patients. (Crohn's Disease = CD)

Disclosures:

Justin Field indicated no relevant financial relationships.

Ryan Ungaro: AbbVie – Grant/Research Support. Boehringer Ingelheim – Grant/Research Support. Eli Lilly – Consultant. Janssen – Consultant. Pfizer – Consultant, Grant/Research Support. Takeda – Consultant.

Louis Cohen indicated no relevant financial relationships.

Jean-Frederic Colombel: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant. Arena – Consultant. BMS – Consultant. Boehringer Ingelheim – Consultant. Celgene Corporation – Consultant. Celltrion – Personal Fees. Eli Lilly – Consultant. Enterome – Personal Fees. Ferring Pharmaceuticals – Consultant. Galmed Research – Consultant. Galxo Smith Kline – Consultant. Genentech – Consultant. Genfit – Stock Options. Imedex – Consultant. Immunic – Consultant. Intestinal Biotech Development – Stock Options. Intestinal Biotech Development – Stock Options. Iterative Scopes – Consultant. Janssen Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support. Kaleido Biosciences – Consultant. MedImmune – Personal Fees. Merck – Consultant. Microba – Consultant. Novartis – Consultant. PBM Capital – Consultant. Pfizer – Consultant. PPM Services – Personal Fees. Protagonist Therapeutics – Consultant. Sanofi – Consultant. Second Genome – Personal Fees. Seres – Personal Fees. Shire – Personal Fees. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support. Theradiag – Personal Fees. TiGenix – Consultant. Vifor – Consultant.

Justin Field, MD, Ryan Ungaro, MD, MS, Louis Cohen, MD, Jean-Frederic Colombel, MD. E0342 - Characterization of Crohn’s Patients That Are Multiple Primary Non-Responders to Biologic Therapies, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.