P0681 - Corticosteroid-Sparing Effect in Patients With Moderately to Severely Active Ulcerative Colitis Treated With Mirikizumab Maintenance Therapy

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Corey A. Siegel, MD, MS

Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire

David Laharie, ¹, Corey A. Siegel, MD, MS², Karen Samaan, ³, Deborah Fischer, MD³, Nathan Morris, ³, Isabel Redondo, ³, Parambir S. Dulai, MD⁴, Vipul Jairath, MBChB, DPhil⁵, Javier P. Gisbert, MD, PhD⁶, Katsuyoshi Matsuoka, ⁷
¹Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Centre, France; ²Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; ³Eli Lilly and Company, Indianapolis, IN; ⁴Feinberg School of Medicine, Northwestern University, Chicago, IL; ⁵Western University, London, ON, Canada; ⁶Hospital Universitario de La Princesa, Madrid, Madrid, Spain; ⁷Toho University Sakura Medical Center, Sakura, Chiba, Japan

Introduction: Corticosteroid (CS)-free remission is a treatment goal for patients with ulcerative colitis (UC). Mirikizumab’s (miri) CS-sparing effect was assessed in the LUCENT-2 maintenance trial among patients receiving CS at baseline (BL).

Methods: In LUCENT-1, patients on miri or placebo (PBO) who entered the study on CS remained on their stable BL dose (≤20mg/day prednisone equivalent) during induction (Week [W] 0 to W12). Patients randomized to miri induction and achieving clinical response (N=365) at W12 were re-randomized 2:1 in LUCENT-2 to miri (200mg/4 weeks) or PBO for maintenance (W12-52). LUCENT-1 responders began a CS taper upon entering LUCENT-2 by tapering the >10mg daily dose by 5mg/week until receiving 10mg/day, and then 2.5mg/week until 0mg/day. For those receiving ≤10mg/day, the daily dose was tapered by 2.5 mg/week until 0mg/day. Clinical remission was defined as a Mayo stool frequency subscore of 0 or 1 with ≥1-point decrease from W0 BL, a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 (excluding friability). Descriptive statistics were calculated with non-responder imputation used for missing data. The common risk difference between miri and PBO was calculated and adjusted for the following stratification factors: prior biologic/tofacitinib failure, region, and W12 clinical remission status.

Results: Of the miri induction responders who were re-randomized in LUCENT-2, 33% (59/179) of PBO patients were BL CS users compared with 34% (125/365) of miri patients. The median BL CS dose was 20 mg/day. At W52, a significantly greater proportion of patients treated with maintenance miri vs PBO, achieved clinical remission while off CS, clinical remission + off CS for ≥12 weeks, and clinical remission + symptomatic remission at W40 +off CS for ≥12 weeks (Table; all p≤0.01). A significantly greater proportion of patients treated with miri permanently discontinued CS by W24, W40, and W52 vs PBO (Table; all p< 0.001) and among patients who completed W52 of miri treatment, 95.2% permanently discontinued CS by W52.

Discussion: Among patients on CS at BL, miri induction responders who were re-randomized to miri maintenance achieved CS-free clinical remission at W52 at higher rates than miri induction responders who were re-randomized to PBO maintenance. Mirikizumab’s CS-sparing effect in patients with moderately to severely active UC is clinically meaningful and aligned with long-term treatment goals of CS discontinuation.

	Mirikizumab N=125	Placebo N=59	Common risk difference (95% CI)	P-value
Patients achieving clinical remission
Clinical remission and off CS at Week 52	52 (41.6%)	9 (15.3%)	22.3 (9.9–34.6)	p=0.002
Clinical remission at Week 52 and off CS for ≥12 weeks	51 (40.8%)	9 (15.3%)	21.2 (8.9–33.4)	p=0.003
Clinical remission at Week 52 with symptomatic remission at Week 40 and off CS for ≥12 weeks	48 (38.4%)	7 (11.9%)	21.9 (10.7–33.2)	p=0.002
Patients permanently off CS by week*
Off CS at Week 52 among treatment completers	99/104 (95.2%)	26/30 (86.7%)	NA**	NA**
Off CS at Week 52	99 (79.2%)	26 (44.1%)	34.2 (19.2–49.2)	p< 0.001
Off CS at Week 40	96 (76.8%)	25 (42.4%)	33.1 (18.0–48.3)	p< 0.001
Off CS at Week 24	88 (70.4%)	23 (39.0%)	30.5 (15.2–45.8)	p< 0.001
Abbreviations: CI = confidence interval; CS = corticosteroid; N = number of patients in group. Risk difference CI were calculated with the Mantel-Haenszel-Sato method. P-values were calculated with the Cochran-Mantel-Haenszel test adjusted by prior biologic/tofacitinib failure and Week 0 CS use. Non-responder imputation was used for missing data. Patients who discontinued study treatment or received rescue treatment were defined as treatment failures (i.e., remaining on CS). Patients were off CS and did not discontinue study treatment or re-initiate CS use for the remainder of the study period. *NA = not available. Formal treatment comparison for this endpoint not performed because this is an observed analysis.

Table: Table. Corticosteroid-Sparing Effects in Patients on Baseline Systemic Corticosteroids Treated with Mirikizumab vs Placebo

Disclosures:

David Laharie: Abbvie – Advisory Committee/Board Member. Galapagos – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Lilly – Advisor or Review Panel Member, Advisory Committee/Board Member. MSD – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member.

Corey Siegel: Abbvie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. BMS – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Fresnius – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Consultant/advisory board, speaker for CME activities. Napo Pharmaceuticals – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, speaker for CME activities. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau.

Karen Samaan: Eli Lilly and Company – Employee, Stock Options.

Deborah Fischer: Eli Lilly and Company – Employee, Stock Options.

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

Isabel Redondo: Eli Lilly and Company – Employee.

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.

Vipul Jairath: AbbVie – Advisory Committee/Board Member, consulting/advisory board fees, speaker’s fees. Alimentiv Inc – consulting/advisory board fees. Arena pharmaceuticals – consulting/advisory board fees. Asahi Kasei Pharma – consulting/advisory board fees. Asieris – consulting/advisory board fees. Astra Zeneca – consulting/advisory board fees. Bristol Myers Squibb – consulting/advisory board fees, speaker’s fees. Celltrion – consulting/advisory board fees. Eli Lilly and Company – consulting/advisory board fees. Ferring – consulting/advisory board fees, speaker’s fees. Flagship Pioneering – consulting/advisory board fees. Fresenius Kabi – consulting/advisory board fees, speaker’s fees. Galapagos – consulting/advisory board fees, speaker’s fees. Genentech – consulting/advisory board fees. Gilead – consulting/advisory board fees. GlaxoSmithKline – consulting/advisory board fees. Janssen – consulting/advisory board fees, speaker’s fees. Merck – consulting/advisory board fees. Metacrine – consulting/advisory board fees. Mylan – consulting/advisory board fees. Pandion – consulting/advisory board fees. Pendopharm – consulting/advisory board fees. Pfizer – consulting/advisory board fees, speaker’s fees. Prometheus – consulting/advisory board fees. Protagonist – consulting/advisory board fees. Reistone Biopharma – consulting/advisory board fees. Roche – consulting/advisory board fees. Sandoz – consulting/advisory board fees. Second Genome – consulting/advisory board fees. Shire – speaker’s fees. Sorriso pharmaceuticals – consulting/advisory board fees. Takeda – consulting/advisory board fees, speaker’s fees. Teva – consulting/advisory board fees. Topivert – consulting/advisory board fees. Ventyx – consulting/advisory board fees. Vividion – consulting/advisory board fees.

Javier Gisbert: Abbvie – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Biogen – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Casen Fleet – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Celgene/Bristol Myers – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Chiesi – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Dr. Falk Pharma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Eli Lilly – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Faes Farma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Ferring – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Gebro Pharma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Gilead/Galapagos – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Janssen – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Kern Pharma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. MSD – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Mylan – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Norgine – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Otsuka Pharmaceutical – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Pfizer – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Roche – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Sandoz – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Shire Pharmaceuticals – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Tillotts Pharma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau. Vifor Pharma – Advisor or Review Panel Member, Consultant, Grant/Research Support, Speakers Bureau.

Katsuyoshi Matsuoka: AbbVie, EA Pharma, Eli Lilly and Company, JIMRO – Grant/Research Support. AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyorin, – Speakers Bureau. Kissei Pharmaceutical, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon, and Zeria Pharmaceutical – Grant/Research Support. Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon,Takeda, and Zeria Pharmaceutical – Speakers Bureau.

David Laharie, ¹, Corey A. Siegel, MD, MS², Karen Samaan, ³, Deborah Fischer, MD³, Nathan Morris, ³, Isabel Redondo, ³, Parambir S. Dulai, MD⁴, Vipul Jairath, MBChB, DPhil⁵, Javier P. Gisbert, MD, PhD⁶, Katsuyoshi Matsuoka, ⁷. P0681 - Corticosteroid-Sparing Effect in Patients With Moderately to Severely Active Ulcerative Colitis Treated With Mirikizumab Maintenance Therapy, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.