P0738 - The Addition of Bowel Urgency Improvement to the Achievement of Clinical Response or Remission Was Associated with Better Work Productivity in Patients with Ulcerative Colitis from Mirikizumab Phase 3 Trials

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

David Rubin, MD, FACG

University of Chicago Medicine, Inflammatory Bowel Disease Center
Chicago, IL

David T. Rubin, MD¹, Jianmin Wu, PhD², Bomina Park, ², Simin Baygani, MS², Nathan Morris, ², Theresa Hunter Gibble, PhD, MPH², Stefan Schreiber, MD³
¹Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; ²Eli Lilly and Company, Indianapolis, IN; ³University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

Introduction: This analysis evaluated if the addition of BU improvement to clinical response or remission was associated with better work productivity from mirikizumab (miri) Phase 3 LUCENT-1 and LUCENT-2 trials in patients with moderately-to-severely active ulcerative colitis (UC).

Methods: In LUCENT-1, patients were randomized 3:1 to induction miri 300mg intravenous or placebo every four weeks (Q4W). Patients who achieved clinical response to miri at week 12 (W12) were re-randomized 2:1 to maintenance subcutaneous injection of miri 200mg or placebo Q4W for 40 weeks in LUCENT-2 [52 weeks (W52) continuous treatment]. Clinical response and remission were assessed along with change from baseline (BL) in Work Productivity and Activity Impairment Questionnaire UC (WPAI:UC) domain scores. BU was assessed using the Urgency Numeric Rating Scale (UNRS), with both BU CMI (≥3-point change) and BU remission (UNRS score of 0 or 1), measured in patients with a BL UNRS of ≥3. The association between BU (CMI or remission) with the change of WPAI:UC was evaluated using analysis of variance among patients with BL UNRS ≥3 who achieved clinical response. This analysis was repeated among patients who achieved clinical remission.

Results: The addition of BU CMI was positively associated with reduction of activity impairment, presenteeism, and overall work impairment in patients who achieved clinical response or remission at both W12 and W52 (p< 0.005)(Table 1). Achieving clinical response and BU remission was significantly associated with greater reduction of activity impairment, presenteeism, and overall work impairment vs patients with clinical remission only at both W12 and W52 (p< 0.01). The combined improvement of achieving both clinical remission and BU remission was significantly associated with higher reduction in activity impairment at W12 (-36.1% vs -27.3%; p=0.0147) and overall work impairment at W52 (-39.9% vs -29.8%; p=0.0394). Patients who achieved both clinical response or clinical remission and BU CMI or BU remission did not show a significant difference in absenteeism compared to those who achieved clinical response or remission alone.

Discussion: Among patients with UC from miri phase 3 trials, the addition of BU (CMI or remission) to the achievement of clinical response or remission was associated with reduction of WPAI:UC components: activity impairment, presenteeism, and overall work impairment.

	Activity Impairment (Change from baseline at W12), p-value*		Absenteeism (Change from baseline at W12), p-value*		Presenteeism (Change from baseline at W12), p-value*		Overall Work Impairment (Change from baseline at W12), p-value*		Activity Impairment (Change from baseline at W52), p-value*			Absenteeism (Change from baseline at W52), p-value*			Presenteeism (Change from baseline at W52), p-value*			Overall Work Impairment (Change from baseline at W52), p-value*
Clinical Response + BU CMI¹	-32.15 ( 24.47)		-10.94 ( 30.46)		-28.66 ( 22.85)		-29.77 ( 25.37)		-41.21 ( 25.10)		-12.40 ( 27.30)			-36.82 ( 24.18)			-38.25 ( 26.25)
Clinical Response - BU CMI²	-17.11 ( 26.39)	< .0001	-9.45 ( 22.11)	0.634	-14.43 ( 24.64)	< .0001	-17.19 ( 26.48)	< .0001	-27.26 ( 27.35)	< .0001	-10.85 ( 26.03)		0.7116	-19.62 ( 24.09)		< .0001	-21.18 ( 28.03)		< .0001
Clinical Response + BU Remission³	-34.52 ( 24.63)		-10.31 ( 27.38)		-29.72 ( 22.76)		-31.05 ( 24.91)		-41.94 ( 25.59)		-11.64 ( 24.31)			-36.96 ( 23.91)			-39.55 ( 25.44)
Clinical Response - BU Remission⁴	-23.30 ( 26.13)	< .0001	-10.46 ( 27.98)	0.9635	-20.33 ( 24.74)	0.0012	-22.23 ( 26.75)	0.0048	-33.81 ( 26.42)	0.0034	-12.35 ( 29.33)		0.8462	-27.82 ( 25.83)		0.0096	-28.15 ( 28.76)		0.0031
Clinical Remission + BU CMI⁵	-35.03 ( 23.87)		-14.17 ( 27.32)		-31.83 ( 22.93)		-34.37 ( 25.77)		-44.05 ( 24.25)		-14.54 ( 28.78)			-37.47 ( 24.09)			-39.76 ( 25.70)
Clinical Remission - BU CMI⁶	-18.64 ( 29.80)	< .0001	-6.30 ( 17.37)	0.1334	-15.00 ( 29.68)	0.0015	-17.28 ( 30.59)	0.0031	-31.71 ( 23.12)	0.0035	-10.49 ( 28.23)		0.5077	-20.77 ( 21.34)		0.0016	-21.41 ( 26.58)		0.0016
Clinical Remission + BU Remission⁷	-36.07 ( 23.09)		-12.72 ( 27.29)		-32.50 ( 21.41)		-34.91 ( 24.60)		-43.10 ( 25.38)		-12.13 ( 24.79)			-37.37 ( 24.79)			-39.91 ( 26.14)
Clinical Remission -BU Remission⁸	-27.30 ( 28.01)	0.0147	-12.00 ( 24.22)	0.8744	-24.23 ( 28.01)	0.0772	-26.75 ( 29.76)	0.109	-39.66 ( 23.12)	0.3134	-15.94 ( 33.46)		0.4496	-28.78 ( 23.15)		0.0545	-29.80 ( 27.03)		0.0394
Note: data is represented as mean (SD), unless otherwise noted. N-values (W12: Activity Impairment, Absenteeism, Presenteeism, Overall Work Impairment; W52: Activity Impairment, Absenteeism, Presenteeism, Overall Work Impairment: 1: W12: 396, 220 , 220 , 220; W52: 272, 160 , 160 , 160. 2: W12: 225, 122 , 122 , 122; W52: 84, 56 , 56 , 56. 3: W12: 188, 114 , 114 , 114; W52: 180, 106 , 106 , 106. 4: W12: 433, 228 , 228 , 228; W52: 176, 110 , 110 , 110. 5: W12: 167, 100 , 100 , 100; W52: 173, 106 , 106 , 106. 6: W12: 59, 31 , 31 , 31; W52: 41, 28 , 28 , 28. 7: W12: 89, 56 , 56 , 56; W52: 126, 79 , 79 , 79. 8: W12: 137, 75 , 75 , 75; W52: 88, 55 , 55 , 55. BU = Bowel Urgency; CMI=Bowel Urgency Clinical Meaningful Improvement; SD: standard deviation; W12: week 12; W52: week 52. Clinical remission: stool frequency subscore = 0 or 1 with a ≥1-point decrease from baseline; rectal bleeding (RB) subscore = 0; and endoscopic subscore = 0 or 1. Clinical response: ≥2-point and ≥30% decrease in the modified Mayo Score from baseline, RB = 0 or 1, or ≥1-point decrease from baseline. **Evaluated using ANOVA (Analysis of variance) model including BU CMI (yes/no) or BU remission (yes/no). P-values less than 0.05 are bolded.*

Table: Association of Clinical Remission/Response with achievement of Bowel Urgency Remission/CMI on Change from Baseline of WPAI:UC Domain Scores in Patients with UC at W12 and W52 of Continuous Treatment

Disclosures:

David Rubin: AbbVie – Consultant, personal fees. AltruBio – Consultant, personal fees. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene Chronicles – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Corp/Syneos – Consultant. Eco R1 – Consultant. GastroIntestinal Research Foundation – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, personal fees. Helmsley Charitable Trust – Grant/Research Support. Iterative Health – Consultant. Janssen Pharmaceuticals – Consultant, personal fees. Kaleido Biosciences – Consultant. Lilly – Consultant. Pfizer – Consultant, personal fees. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant, personal fees. Seres Therapeutics – Consultant. Takeda – Consultant, Grant/Research Support, Personal fees. Target RWE – Consultant. Trellus Health – Consultant.

Jianmin Wu: Eli Lilly and Company – Employee, Stock Options.

Bomina Park: Eli Lilly and Company – Employee, Stock Options.

Simin Baygani: Eli Lilly and Company – Employee, Stock Options.

Nathan Morris: Eli Lilly and Company – Employee, Stock Options.

Theresa Hunter Gibble: Eli Lilly and Company – Employee, stockholder.

Stefan Schreiber: AbbVie – Personal fees. Amgen – Personal fees. Arena Pharmaceuticals – Personal fees. Biogen – Personal fees. Bristol Myers Squibb – Personal fees. Celgene – Personal fees. Celltrion Healthcare – Personal fees. Dr. Falk Pharma – Personal fees. Eli Lilly – personal fees. Ferring Pharmaceuticals – personal fees. Fresenius Kabi – Personal fees. Galapagos – Personal fees. Gilead – Personal fees. Hikma Pharmaceuticals – Personal fees. I-Mab – Personal fees. Janssen Pharmaceuticals – Personal fees. Morphic – Personal fees. MSD – Personal fees. Mylan – Personal fees. Pfizer – Personal fees. Protagonist – Personal fees. ProventionBio – Personal fees. Sandoz/Hexal – personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. UCB – personal fees.

David T. Rubin, MD¹, Jianmin Wu, PhD², Bomina Park, ², Simin Baygani, MS², Nathan Morris, ², Theresa Hunter Gibble, PhD, MPH², Stefan Schreiber, MD³. P0738 - The Addition of Bowel Urgency Improvement to the Achievement of Clinical Response or Remission Was Associated with Better Work Productivity in Patients with Ulcerative Colitis from Mirikizumab Phase 3 Trials, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.