B0408 - Improvement in Fatigue With Mirikizumab Therapy Is Associated With Clinical Remission and Pain Improvements but Not With Endoscopic Response in Patients With Moderately-to-Severely Active Crohn’s Disease

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Miguel Regueiro, MD

Cleveland Clinic Main Campus
Cleveland, Ohio

Miguel Regueiro, MD¹, Monika Fischer, MD, MSc², David T. Rubin, MD, FACG³, Toshifumi Hibi, MD, PhD⁴, Peter Bossuyt, MD⁵, Pascal Juillerat, MD, MSc⁶, Paul Pollack, MD⁷, Xian Zhou, ⁸, Marijana Protic, MD, PhD⁷, Theresa Hunter Gibble, PhD⁷, Lai-Shan Chan, MSc⁷, Hilde Carlier, ⁷, Pieter Hindryckx, MD, PhD⁹
¹Cleveland Clinic Main Campus, Cleveland, OH; ²Indiana University, Indianapolis, IN; ³University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL; ⁴Center for Advanced IBD Research and Treatment Kitasato, University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan; ⁵Imelda General Hospital, Bonheiden, Brussels Hoofdstedelijk Gewest, Belgium; ⁶Crohn's and Colitis Center, Beaulieu Gastroenterology; Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; ⁷Eli Lilly and Company, Indianapolis, IN; ⁸Syneos Health, Morrisville, NC; ⁹Ghent University Hospital, Ghent, Vlaams-Brabant, Belgium

Introduction: Fatigue is common in patients (pts) with Crohn’s disease (CD) and negatively impacts quality of life. We previously reported that fatigue improved in pts with CD receiving mirikizumab (miri) in the AMAG study in all treatment arms. The association between changes in clinical and inflammatory markers and changes in fatigue might reveal the mechanism of fatigue relief.

Methods: 191 moderately-to-severely active CD pts were randomized 2:1:1:2 into 4 treatment arms (placebo [PBO], 200mg, 600mg, 1000mg miri), administered intravenously every 4 weeks at Weeks (W) 0, 4, 8. At W12 pts were switched from PBO to miri and rerandomized between miri doses based on response. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Endoscopic response was defined as ≥50% reduction from baseline in total Simplified Endoscopic Activity Score for Crohn’s Disease. For continuous variables, Pearson’s correlation coefficients, 95% confidence intervals, and p-values were calculated. Cohen’s conventions were used to assess strength of correlations. Analysis of covariance was used to assess relationship between change in FACIT-F and endoscopic response at the same timepoint adjusting for baseline FACIT-F values. Data were pooled for all treatment arms including PBO.

Results: Mean change in FACIT-F scores for pts with and without endoscopic response at W12 were 8.1 and 7.2, respectively (p=0.33) and at W52 were 13.9 and 13.7, respectively (p=0.54). At W12, change in FACIT-F showed moderate but statistically significant correlation with change at the same timepoint in Crohn’s Disease Activity Index (CDAI) total score, abdominal pain, and stool frequency. Weak but statistically significant correlations were observed with calprotectin, and C-reactive protein (Table). At W52, change in FACIT-F was moderately but significantly correlated with change in CDAI total score, abdominal pain, and stool frequency (Table).

Discussion: Considering the limitation of the posthoc analysis and design of this Phase 2 trial, improvements in fatigue were significantly associated with improvement in CDAI score, abdominal pain, and stool frequency in patients with CD. Although fatigue has been hypothesized to be mediated in part by inflammatory cytokines, our data showed no consistent relationship of improvement in fatigue with changes in objective markers of disease activity, suggesting the possibility of alternative or additional mechanistic processes for fatigue in CD.

	Week 12 (N=191)			Week 52 (N=176)
Clinical measure	Pearson corr	95% CI	p-value	Pearson corr	95% CI	p-value
CDAI total score	-0.404	(‑0.530, ‑0.259)	< 0.0001	-0.492	(‑0.614, ‑0.346)	< 0.0001
SES-CD total score	-0.146	(-0.290, 0.004)	0.0572	-0.076	(‑0.238, 0.090)	0.3702
Hematocrit (%)	-0.039	(-0.194, 0.119)	0.6319	0.152	(-0.016, 0.312)	0.0756
Hemoglobin	-0.011	(-0.167, 0.145)	0.8916	0.120	(-0.049, 0.282)	0.1638
Fecal calprotectin (log)	-0.269	(‑0.419, ‑0.105)	0.0015	-0.175	(-0.342, 0.003)	0.0544
C-reactive protein (log)	-0.165	(‑0.310, ‑0.013)	0.0331	-0.151	(-0.310, 0.016)	0.0756
Abdominal pain average score	-0.380	(‑0.504, ‑0.240)	< 0.0001	-0.438	(-0.565, -0.292)	< 0.0001
Stool frequency average score	-0.354	(‑0.481, ‑0.212)	< 0.0001	-0.290	(-0.437, -0.128)	0.0006
Abbreviations: CDAI=Crohn’s Disease Activity Index; corr=correlation; N=number of patients in the analysis (including patients with non-missing change scores); FACIT-F=Functional Assessment of Chronic Illness Therapy-Fatigue; SES-CD=Simplified Endoscopic Activity Score for Crohn’s Disease.

Table: Table. Correlation of change in FACIT-F with change in clinical measures

Disclosures:

Miguel Regueiro: Abbvie – Advisory Committee/Board Member, Consultant. Abbvie – Grant/Research Support. ALFASIGMA, S.p.A. – Advisory Committee/Board Member. Allergan – Advisory Committee/Board Member. Amgen – Advisory Committee/Board Member. BMS – Grant/Research Support. Bristol Meyer Squibb – Advisory Committee/Board Member, Consultant. CC360 – Royalties. Celgene – Advisory Committee/Board Member. CME Outfitters – CME Companies. Cornerstones – CME Companies. Crohn’s and Colitis Foundation as Editor-in-Chief – Royalties. Genentech – Advisory Committee/Board Member. Genentech – Grant/Research Support. Gilead – Advisory Committee/Board Member. Gilead – Grant/Research Support. HMPGlobal – CME Companies. Imedex, GI Health Foundation (GiHF) – CME Companies. Janssen – Advisory Committee/Board Member, Consultant. Janssen – Grant/Research Support. Lilly – Grant/Research Support. MDEducation – CME Companies. Medscape – CME Companies. Miraca Labs – Advisory Committee/Board Member. MJH life sciences – CME Companies. Pfizer – Advisory Committee/Board Member, Consultant. Prometheus – Advisory Committee/Board Member. Remedy – CME Companies. Salix – Advisory Committee/Board Member. Seres – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Consultant. TARGET Pharma Solutions – Advisory Committee/Board Member. UCB – Grant/Research Support. WebMD – CME Companies. Wolters Kluwer Health as Author/Editor of UpToDate – Royalties.

Monika Fischer: AbbVie – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Rebiotix – Data and safety monitoring board. Scioto Biosciences – Advisory Committee/Board Member, Consultant.

David Rubin: AbbVie – Consultant. Alimentiv Inc. – Consultant. AltruBio – Consultant. Arena Pharmaceuticals – Consultant. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim, Ltd. – Consultant. Bristol Myers Squibb – Consultant. Celgene Corp/Syneos – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. EcoR1 – Consultant. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Ironwood Pharmaceuticals – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Kaleido Biosciences – Consultant. Lilly, Eli & Co – Consultant. Materia Prima – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant. Seres Therapeutics, Inc – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Techlab – Consultant. Trellus Health – Consultant.

Toshifumi Hibi: Abbvie GK – Consultant, Grant/Research Support. Activaid – Grant/Research Support. Alfresa Pharma Corporation – Grant/Research Support. Apo Puls Station – Consultant. Bristol-Myaers Squibb – Consultant, Grant/Research Support. Celltrion – Consultant. EA Pharma – Consultant. Eli Lilly and Company – Consultant, Grant/Research Support. Ferring Pharmaceuticals – Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Janssen – Consultant, Grant/Research Support. JMDC Inc – Grant/Research Support. Kyorin – Consultant. Mitsubishi-TanabePharma – Consultant. Mochida Pharmaceutical Co – Grant/Research Support. Nichi-IkoPharmaceutical – Consultant. Nippon Kayaku Co. – Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Takeda Pharmaceutical – Consultant, Grant/Research Support. Zeria Pharmaceutical – Consultant.

Peter Bossuyt: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Amgen – Grant/Research Support. Arena Pharmaceuticals – Advisory Committee/Board Member. Bristol-Myers Squibb(BMS) – Advisory Committee/Board Member. Celltrion – Speakers Bureau. Eli Lilly – Advisory Committee/Board Member. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Merck/MSD – Advisory Committee/Board Member. Mundipharma – Advisory Committee/Board Member, Grant/Research Support. Mylan – Grant/Research Support. Pentax Medical – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. PSI CRO – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau.

Pascal Juillerat: AbbVie – Advisory Committee/Board Member. Amgen – Advisory Committee/Board Member. Arena – Advisory Committee/Board Member. BMS – Advisory Committee/Board Member. Eli Lilly and Company – Advisory Committee/Board Member. Ferring – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. MSD – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member. Pierre Fabre – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member. Tillotts – Advisory Committee/Board Member. UCB Pharma – Advisory Committee/Board Member. Vifor – Grant/Research Support.

Paul Pollack: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Xian Zhou indicated no relevant financial relationships.

Marijana Protic: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Theresa Hunter Gibble: Eli Lilly and Company – Employee.

Lai-Shan Chan: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Hilde Carlier: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Pieter Hindryckx: AbbVie – Advisory Committee/Board Member, Consultant. Falk Pharma – Honoraria. Janssen – Advisory Committee/Board Member, Consultant, Honoraria. Medtronics – Consultant. Mylan – Honoraria. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Honoraria.