P0724 - Group-Based Trajectory Modeling to Identify Response Patterns to Ozanimod Treatment in Patients With Ulcerative Colitis

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

PD

Parambir Dulai, MD

Feinberg School of Medicine, Northwestern University
Chicago, Illinois

Parambir S. Dulai, MD¹, Brian G. Feagan, MD², Bruce E. Sands, MD, MS, FACG³, Florian Rieder, MD⁴, Joana Torres, MD, PhD⁵, Zhaohui Liu, PhD⁶, Anjali Jain, PhD⁶, Hsiuanlin Wu, MS⁶, Maria T. Abreu, MD⁷, Stefan Schreiber, MD⁸
¹Feinberg School of Medicine, Northwestern University, Chicago, IL; ²Western University, London, ON, Canada; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Cleveland Clinic, Cleveland, OH; ⁵Hospital da Luz; Hospital Beatriz Ângelo; and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Lisboa, Portugal; ⁶Bristol Myers Squibb, Princeton, NJ; ⁷University of Miami Miller School of Medicine, Miami, FL; ⁸University Hospital Schleswig Holstein, Kiel, Schleswig-Holstein, Germany

Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3 True North (TN; NCT02435992) study, patient (pt) responses to OZA were heterogenous at Week (W) 52.

Methods: This TN post hoc analysis used group-based trajectory modeling (GBTM) to identify patterns of OZA response trajectories during the TN maintenance period (MP) in W10 OZA clinical responders who were rerandomized to continue OZA (OZA/OZA arm; n=230) in MP. Change from baseline (BL; TN W0) in partial Mayo score (PMS) was used as a variable for identifying pt clusters with various OZA response patterns. GBTM, determined by maximum likelihood estimation, was used to estimate OZA response trajectories. After modeling, clinical and mucosal outcomes at W52 were compared in the GBTM-identified pt clusters.

Results: Of 230 pts in the MP OZA/OZA arm, 1 did not have post-BL PMS data available and was excluded from this analysis; 5 groups of pt-response patterns to OZA therapy were identified during MP. At W10, a PMS response was observed in all 5 trajectory groups (TGs). During the 42-wk MP, TGs diverged into fast sustained improvement (Group [G] 1; n=38 [16.6%, 38/229]); slow sustained improvement (G2; n=85 [37.1%, 85/229]); gradual improvement (G3; n=60 [26.2%, 60/229]); fast rebound (G4; n=25 [10.9%, 25/229]); and slow rebound (G5; n=21 [9.2%, 21/229]). All pts entering the MP were OZA clinical responders, but 20% of pts did not demonstrate sustained improvement from BL in PMS (G4 and G5); 80% demonstrated sustained improvement from BL in PMS (G1–3). From W10 onward, 26.2%, 37.1%, and 16.6% of pts achieved and maintained PMS reductions of ≥3.98, ≥5.27, and ≥6.71 points, respectively. Pts in G4 and G5 were slightly younger at diagnosis and had a higher W10 Geboes histologic index score vs the other TGs; pts in G4 had the most corticosteroid use at screening (Table). At W52, more pts in G1–3 combined achieved clinical response (74%) and clinical remission (46%) vs those in G4 and G5 combined (7% and 2%, respectively). G1–3 combined had more pts with endoscopic improvement (56%) and mucosal healing (37%) at W52 vs G4 and G5 combined (7% and 2%, respectively).

Discussion: Five groups of pt-response trajectories to OZA tx were identified; 80% of pts in G1–3 had sustained response to OZA tx. GBTM identified clinically meaningful pt subgroups by pt-response patterns to OZA tx. This approach needs to be validated in prospective studies.

	G1: Fast sustained improvement (n=38; 6.6% [38/229])	G2: Slow sustained improvement (n=85; 37.1% [85/229])	G3: Gradual improvement (n=60; 26.2% [60/229])	G4: Fast rebound (n=25; 10.9% [25/229])	G5: Slow rebound (n=21; 9.2% [21/229])
Sex, male, n (%)	15 (39.5)	43 (50.6)	33 (55.0)	13 (52.0)	12 (57.1)
Age at UC diagnosis, y, mean (SD)	34.6 (12.4)	35.7 (14.1)	35.3 (13.0)	29.8 (11.5)	31.5 (11.0)
Corticosteroid use at screening, n (%)	11 (28.9)	28 (32.9)	14 (23.3)	11 (44.0)	7 (33.3)
Prior use of tumor necrosis factor antagonist, n (%)	9 (23.7)	28 (32.9)	22 (36.7)	9 (36.0)	7 (33.3)
Complete Mayo score at W10, mean (SD)	2.8 (1.7)	3.5 (1.8)	3.8 (1.9)	4.8 (2.1)	3.7 (1.6)
PMS at W10, mean (SD)	1.3 (1.0)	1.9 (1.2)	2.1 (1.4)	3.0 (1.8)	2.1 (1.2)
Mucosal endoscopy subscore of 2 (moderate) at BL, n (%)	14 (36.8)	39 (45.9)	28 (46.7)	9 (36.0)	8 (37.1)
Mucosal endoscopy subscore of 3 (severe) at BL, n (%)	24 (63.2)	46 (54.1)	32 (53.3)	16 (64.0)	13 (61.9)
Geboes continuous index score at W10, mean (SD)	5.9 (4.3)	5.8 (4.9)	7.0 (5.2)	7.7 (5.1)	7.6 (4.8)

Table. Pt characteristics at BL (TN W0) or W10.

Disclosures:

Parambir S. Dulai: Abbvie – Consultant. Abivax – Consultant. Adiso Therapeutics, Inc – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support. GlaxoSmithKline – Consultant. Janssen – Consultant, Grant/Research Support. Lilly – Consultant. Pfizer – Consultant, Grant/Research Support. PreciDiag – Royalties. Roivant – Consultant. Takeda – Consultant, Grant/Research Support.

Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.

Florian Rieder: 89Bio – Advisory Committee/Board Member, Consultant. Abbvie – Advisory Committee/Board Member, Consultant. Adnovate – Advisory Committee/Board Member, Consultant. Agomab – Advisory Committee/Board Member, Consultant. Allergan – Advisory Committee/Board Member, Consultant. Arena – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. CDISC – Advisory Committee/Board Member, Consultant. Celgene/Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Ferring – Advisory Committee/Board Member, Consultant. Galapagos – Advisory Committee/Board Member, Consultant. Galmed Pharmaceuticals – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant. Gossamer – Advisory Committee/Board Member, Consultant. Guidepoint – Advisory Committee/Board Member, Consultant. Helmsley – Advisory Committee/Board Member, Consultant. Horizon Therapeutics – Advisory Committee/Board Member, Consultant. Image Analysis Limited – Advisory Committee/Board Member, Consultant. Index Pharmaceuticals – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant. Koutif Therapeutics – Advisory Committee/Board Member, Consultant. Mestag Therapeutics – Advisory Committee/Board Member, Consultant. Metacrine – Advisory Committee/Board Member, Consultant. Morphic Therapeutic – Advisory Committee/Board Member, Consultant. Organovo – Advisory Committee/Board Member, Consultant. Origo – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pliant – Advisory Committee/Board Member, Consultant. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Receptos – Advisory Committee/Board Member, Consultant. REDX – Advisory Committee/Board Member, Consultant. Roche – Advisory Committee/Board Member, Consultant. Samsung – Advisory Committee/Board Member, Consultant. Surmodics – Advisory Committee/Board Member, Consultant. Surrozen – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant. TD Cowen – Advisory Committee/Board Member, Consultant. Techlab – Advisory Committee/Board Member, Consultant. Theravance – Advisory Committee/Board Member, Consultant. Thetis Pharmaceuticals – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant. Ysios Capital – Advisory Committee/Board Member, Consultant.

Joana Torres: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member, Speakers Bureau. Janssen – Advisory Committee/Board Member, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Speakers Bureau.

Zhaohui Liu: Bristol Myers Squibb – employee and/or shareholder.

Anjali Jain: Bristol Myers Squibb – employee and/or shareholder.

Hsiuanlin Wu: Bristol Myers Squibb – employee and/or shareholder.

Maria T. Abreu: AbbVie – Advisory Committee/Board Member, Consultant. Alimentiv – Speakers Bureau. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Arena – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celsius Therapeutics – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Gilead Sciences – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Microba Life Sciences, – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Takeda – Speakers Bureau. UCB Biopharma – Advisory Committee/Board Member, Consultant. WebMD Global – Advisory Committee/Board Member, Consultant.

Stefan Schreiber: AbbVie – Consultant, Speakers Bureau. Arena – Consultant. Biogen – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb, – Consultant, Speakers Bureau. Celgene – Consultant. Celltrion – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant, Speakers Bureau. Falk Pharma – Consultant, Speakers Bureau. Fresenius – Consultant. Galapagos/Gilead – Consultant, Speakers Bureau. Hikma – Consultant, Speakers Bureau. IMAB – Advisory Committee/Board Member, Consultant. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mylan – Advisory Committee/Board Member, Consultant. Pfizer – Consultant, Speakers Bureau. Protagonist – Consultant. Provention Bio – Consultant. Takeda – Consultant, Speakers Bureau. Theravance – Consultant.

Parambir S. Dulai, MD¹, Brian G. Feagan, MD², Bruce E. Sands, MD, MS, FACG³, Florian Rieder, MD⁴, Joana Torres, MD, PhD⁵, Zhaohui Liu, PhD⁶, Anjali Jain, PhD⁶, Hsiuanlin Wu, MS⁶, Maria T. Abreu, MD⁷, Stefan Schreiber, MD⁸. P0724 - Group-Based Trajectory Modeling to Identify Response Patterns to Ozanimod Treatment in Patients With Ulcerative Colitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.