P2210 - Mirikizumab Sustained Improvement on Fatigue in Patients with Moderately to Severely Active Crohn’s Disease in the Phase 2 AMAG Study at Week 104

Monday, October 23, 2023

10:30 AM – 4:15 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Miguel Regueiro, MD

Cleveland Clinic Lerner College of Medicine, Case Western Reserve University
Cleveland, Ohio

Miguel Regueiro, MD¹, Monika Fischer, MD, MSc, FACG², Peter Bossuyt, MD, PhD³, Kim McGinnis, CPNP⁴, Theresa Hunter Gibble, PhD, MPH⁴, Marijana Protic, MD, PhD⁴, Tommaso Panni, PhD⁴, Toshifumi Hibi, MD, PhD⁵, David T. Rubin, MD⁶
¹Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH; ²Indiana University, Indianapolis, IN; ³Imelda GI Clinical Research Center, Bonheiden, Antwerpen, Belgium; ⁴Eli Lilly and Company, Indianapolis, IN; ⁵Kitasato University, Minato City, Tokyo, Japan; ⁶Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL

Introduction: Fatigue is a debilitating, underrecognized, multifactorial symptom experienced by many patients with Crohn’s disease (CD). Mirikizumab (miri) is an anti-IL23p19 antibody that has demonstrated improvement in fatigue in patients with CD in the Phase 2 study (SERENITY/NCT02891226) up to Week 52 (W52). Here we evaluated the sustained effect of miri on fatigue, and the association between changes in select patient-reported outcomes (PROs) and changes in fatigue up to W104.

Methods: Patients (N=191) were randomized using a 2:1:1:2 allocation across 4 treatment arms (placebo (PBO), 200, 600, and 1000mg miri, intravenously (IV) every 4 weeks (Q4W) at W0, W4, and W8). Patients who received miri and achieved ≥1 point improvement in Simple Endoscopic Score for Crohn’s Disease (SES-CD) at W12 were rerandomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (IV-C) or to 300mg miri subcutaneous (SC) Q4W (IV-SC) up to W52. W12 endoscopic non-improvers (NI) and those receiving PBO during induction received IV 1000mg miri Q4W from W12-W52. Subjects reported to experience clinical benefit received 300 mg SC from W52-W104. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Observed changes in FACIT-F from baseline were evaluated up to W104 and analyzed with a mixed model for repeated measures (MMRM) up to W12 and descriptively afterward. FACIT-F associations with PROs and clinical measures were assessed using the Pearson correlation coefficient at W52 and W104.

Results: At W12, all miri groups had improved FACIT-F scores compared to PBO, where the improvement was maintained at W52 and W104 (Figure A-C). Change in FACIT-F at W52 and W104 showed strong correlations with changes at the same timepoint in IBDQ total score, IBDQ bowel symptoms, systemic symptoms, emotional function, and social function domains, as well as the SF-36 Mental and Physical Component Summary scores. Moderate correlations were seen with changes in the Patient’s Global Rating of Severity, abdominal pain, and CDAI total score at W52 and W104 (Table).

Discussion: Treatment with miri was associated with significantly improved FACIT-F scores that were sustained through W104. Interestingly, improvement in fatigue correlated better with emotional, social, and mental well-being (strong correlation) than with disease-related symptoms such as abdominal pain and CDAI score (moderate correlation) in patients treated with miri at W52 and W104.

Figure: Figure: Change from baseline in FACIT-F in the Induction (A), Maintenance (B), and Extension (C) periods.
Note for A: **Week 12: miri 200mg p<0.001, miri 600mg p=0.004, miri 1000mg p<0.001

Disclosures:

Miguel Regueiro: AbbVie – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Alfasigma – Advisory Committee/Board Member, Consultant. Allergan – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Celgene – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Eli Lilly – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Gilead Sciences – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Janssen – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Miraca Labs – Advisory Committee/Board Member, Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Prometheus – Advisory Committee/Board Member, Consultant. Salix – Advisory Committee/Board Member, Consultant. Seres – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Target RWE – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Wolters Kluwer Health – Royalties.

Monika Fischer: AbbVie – Advisor or Review Panel Member. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Eli Lilly and Company – Advisor or Review Panel Member. Ferring – Advisor or Review Panel Member, DSMB. Janssen – Speakers Bureau. Pfizer – Advisor or Review Panel Member. Rebiotix – DSMB. scioto – Advisor or Review Panel Member. Seres – Advisor or Review Panel Member.

Peter Bossuyt: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Amgen – Grant/Research Support. Arena – Advisory Committee/Board Member. Bristol Myers Squibb – Advisory Committee/Board Member, Speakers Bureau. CAG – Speakers Bureau. Celltrion – Advisory Committee/Board Member, Speakers Bureau. CIRC – Advisory Committee/Board Member. Dr. Falk Benelux – Advisory Committee/Board Member. Eli Lilly and Company – Advisory Committee/Board Member, Speakers Bureau. EPGS – Speakers Bureau. Galapagos – Advisory Committee/Board Member, Speakers Bureau. Globalport – Speakers Bureau. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Materia Prima – Speakers Bureau. Pentax – Advisory Committee/Board Member, Speakers Bureau. Pfizer – Grant/Research Support. PSI-CRO – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Scope – Speakers Bureau. Takeda – Advisory Committee/Board Member, Speakers Bureau. Tetrameros – Advisory Committee/Board Member. Viatris – Grant/Research Support.

Kim McGinnis: Eli Lilly and Company – Employee, Stockholder.

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

Marijana Protic: Eli Lilly and Company – Employee.

Tommaso Panni: Eli Lilly and Company – Employee.

Toshifumi Hibi: AbbVie GK – Consultant, Grant/Research Support, Speakers Bureau. Activaid – Grant/Research Support. Alfresa Pharma – Grant/Research Support. Apo Puls Station – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Grant/Research Support. Celltrion – Advisory Committee/Board Member, Consultant. EA Pharma – Advisory Committee/Board Member, Consultant, Study group sponorship. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. Ferring – Grant/Research Support, Speakers Bureau. Gilead Sciences – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. JIMRO – Study group sponorship, Speakers Bureau. JMDC Inc – Grant/Research Support. Kyorin – Advisory Committee/Board Member, Consultant, Study group sponsorship. Mitsubishi-TanabePharma – Advisory Committee/Board Member, Consultant, Scholarship contributions, Speakers Bureau. Mochida Pharmaceutical – Grant/Research Support, Study group sponorship, Speakers Bureau. Nichi-Iko Pharmaceutical – Advisory Committee/Board Member, Consultant. Nippon Kayaku Co – Grant/Research Support, Scholarship contributions. Otsuka Holdings – Study group sponsorship. Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Pfizer Japan Inc – Grant/Research Support. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Zeria Pharmaceutical – Advisory Committee/Board Member, Consultant, Scholarship contributions and study group sponsorship.

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.

Miguel Regueiro, MD¹, Monika Fischer, MD, MSc, FACG², Peter Bossuyt, MD, PhD³, Kim McGinnis, CPNP⁴, Theresa Hunter Gibble, PhD, MPH⁴, Marijana Protic, MD, PhD⁴, Tommaso Panni, PhD⁴, Toshifumi Hibi, MD, PhD⁵, David T. Rubin, MD⁶. P2210 - Mirikizumab Sustained Improvement on Fatigue in Patients with Moderately to Severely Active Crohn’s Disease in the Phase 2 AMAG Study at Week 104, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.