B0406 - Mirikizumab Demonstrates Sustained Improvement in Fatigue in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies

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, Theresa Hunter Gibble, PhD², Alison Potts Bleakman, MA, PhD², Xingyuan Li, PhD², Nathan Morris, PhD², William J. Eastman, MD²
¹Cleveland Clinic Main Campus, Cleveland, OH; ²Eli Lilly and Company, Indianapolis, IN

Introduction: Fatigue is a significant concern for patients (pts) with ulcerative colitis (UC).¹ Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs placebo (PBO) in adult pts with moderately-to-severely active UC in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.^2,3 Here, we report the effect of miri vs PBO on fatigue.

Methods: In the induction study, pts (N=1162) were randomized (3:1) to intravenous (IV) miri 300 mg or PBO every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 (N=544) in the induction were re-randomized (2:1) to subcutaneous (SC) miri 200 mg or PBO Q4W through W40 in the maintenance study. Fatigue was measured using the Fatigue Numeric Rating Scale (NRS), a single-question patient-reported instrument that measures the “worst fatigue in the past 24 hours” with an 11-point NRS (0 = no fatigue, 10 = fatigue as bad as you can imagine), on an electronic daily diary in LUCENT-1 and W40 of LUCENT-2 studies. The treatment difference in least squares mean (LSM) change from the baseline (W0 of therapy) in Fatigue NRS scores was determined using the analysis of covariance model.

Results: In the induction study, a significant reduction in Fatigue NRS score vs PBO was observed as early as W2 (LSM difference [95% CI]: −0.25 [−0.45, −0.05], p=0.013). The LSM difference from baseline at W12 was −0.69 (−0.98, −0.40; p< 0.001). In the maintenance study, a significant reduction in Fatigue NRS score compared to PBO was observed from W16 and sustained through W40 (−1.10 [−1.53, −0.67]; p< 0.001; Figure).

Discussion: Miri-treated pts with moderately-to-severely active UC showed early (W2) and sustained (W40) improvements in fatigue compared to PBO.

¹Huppertz-Hauss G, et al. Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: the IBSEN study. Scand J Gastroenterol. 2017;52:351–358.

²G D’Haens, et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study. J Crohn's Colitis. 2022;16:i028–29.

³M Dubinsky, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Abs. 867e. Digestive Disease Week, May 21-24, 2022.

Figure: Figure. Change from Baseline in Fatigue NRS during A. Induction and B. Maintenance. *p<0.05; **p<0.001 vs placebo
Fatigue NRS score was collected as a single measurement at each visit from W4 to W36 in LUCENT-2.
Weekly measures were calculated by averaging data from all available daily diary entries of Fatigue NRS scores for a 7-day period.
The baseline value for both induction and maintenance was calculated from daily diary entries the week prior to W0 of induction.

Abbreviations: NRS, Numeric Rating Scale; miri, mirikizumab; PBO, placebo; IV, intravenous; SC, subcutaneous

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.

Theresa Hunter Gibble: Eli Lilly and Company – Employee.

Alison Potts Bleakman: Eli Lilly and Company – Employee.

Xingyuan Li: Eli Lilly and Company – Employee.

Nathan Morris: Eli Lilly and Company – Employee.

William Eastman: Eli Lilly and Company – Employee.

Miguel Regueiro, MD¹, Theresa Hunter Gibble, PhD², Alison Potts Bleakman, MA, PhD², Xingyuan Li, PhD², Nathan Morris, PhD², William J. Eastman, MD². B0406 - Mirikizumab Demonstrates Sustained Improvement in Fatigue in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.