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Clinical Trial
. 2024 Nov 4;18(11):1845-1856.
doi: 10.1093/ecco-jcc/jjae088.

Early and Sustained Symptom Control with Mirikizumab in Patients with Ulcerative Colitis in the Phase 3 LUCENT Programme

Silvio Danese  1 , Axel Dignass  2 , Katsuyoshi Matsuoka  3 , Marc Ferrante  4 , Millie Long  5 , Isabel Redondo  6 , Richard Moses  6 , Sebastian Maier  6 , Theresa Hunter Gibble  6 , Nathan Morris  6 , Catherine Milch  6 , Maria T Abreu  7
Affiliations
Clinical Trial

Early and Sustained Symptom Control with Mirikizumab in Patients with Ulcerative Colitis in the Phase 3 LUCENT Programme

Silvio Danese et al. J Crohns Colitis. .

Abstract

Background and aims: Ulcerative colitis [UC], a chronic inflammatory bowel disease, may manifest with symptoms of increased stool frequency [SF], rectal bleeding [RB], bowel urgency [BU], abdominal pain [AP], and fatigue. Mirikizumab, an anti-IL-23p19 antibody, demonstrated efficacy and safety in patients with moderately to severely active UC in the LUCENT Phase 3 trials. We evaluated mirikizumab's efficacy in achieving symptom control and time to symptom improvement during induction, maintenance of sustained symptom control, 'comprehensive symptom control', defined according to a combination of individual patient-reported outcomes, and prognostic baseline indicators of early symptomatic remission at Week 4.

Methods: The results of LUCENT-1/-2 have previously been reported. Treatment differences for symptomatic endpoints were compared over 52 weeks versus placebo [PBO] and comprehensive symptomatic endpoints at 12 and 52 weeks of continuous treatment. Subgroup analyses were conducted for prior biologic or tofacitinib treatment failure. Prognostic analyses were run using regression analysis.

Results: By Week [W] 2, mirikizumab-treated patients achieved greater reductions in SF, RB, BU, and fatigue versus PBO. At W4, there was a higher rate of AP improvement. At W12, a greater proportion of mirikizumab-treated patients achieved symptomatic remission, RB remission, SF remission, and BU remission/clinically meaningful improvement. Mirikizumab-treated patients sustained symptom control versus placebo patients in maintenance until W52. This treatment effect was shown in patients regardless of prior biologic or tofacitinib failure. Additionally, mirikizumab achieved comprehensive symptom control versus PBO at W12 and W52.

Conclusions: Mirikizumab demonstrated efficacy in achieving and sustaining symptom control and comprehensive symptom control over 52 weeks [NCT03518086; NCT03524092].

Keywords: Comprehensive; symptom; ulcerative colitis.

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Conflict of interest statement

SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB, Vial, Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, Takeda. AD reports fees for participation in clinical trials and review activities such as data monitoring boards, statistical analysis, and endpoint committees from Abivax, AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb/Celgene, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts, and Vifor Pharma; payment from lectures, including service on speakers’ bureaus, from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Falk Foundation, Takeda, Thieme, and UniMed. KM received research grants from AbbVie, Mochida, Nippon Kayaku, Zeria, and JIMRO; speakers’ fees from Eli Lilly and Company, Mitsubishi Tanabe Pharma, Takeda, Janssen, AbbVie, EA Pharma, Pfizer, Takeda, Mochida, Kyorin, Zeria, Kissei, Gilead Scientific, Nippon Kayaku, and Celltrion. MF received research grants from AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly and Company, Janssen-Cilag, Medtronic, MRM Health, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare, and Viatris. ML has served as a consultant for AbbVie, Pfizer, Takeda, Lilly, Bristol-Meyers Squibb, Target RWE, and Prometheus; and has received research support from Pfizer, Takeda, and Janssen. IS, RM, SM, THG, and NM are employees of Eli Lilly and Company. CM was an employee of Eli Lilly and Company during the design, conduct, and analyses of the clinical studies. MTA has received research funding from the National Institute of Health, Department of Defense, charities including the Leona M. and Harry B. Helmsley Charitable Trust, Crohn’s and Colitis Foundation, and Kenneth Rainin Foundation; is a consultant or served on advisory boards for AbbVie, Arena Pharmaceuticals [now Pfizer], Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences, Janssen Pharmaceuticals, Janssen Global Services, Pfizer Pharmaceutical, Prometheus Biosciences, and UCB Biopharma SRL; has received fees for lecturing from Alimentiv, Janssen Pharmaceuticals, Prime CME, and WebMD Global LLC.

Figures

Figure 1
Figure 1
Change from baseline LSM [SE] of stool frequency [A], rectal bleeding [B], bowel urgency [C], and fatigue [D] and abdominal pain improvement [E] during induction [% of patients]. Significance level is indicated for MIRI versus PBO at W1 to W12: *p < 0.05, **p < 0.01, ***p ≤ 0.001. BL, baseline; CI, confidence interval; IV, intravenous; LSM, least squares mean; MIRI, mirikizumab; N, number of patients; NRI, non-responder imputation; NRS, numerical rating scale; PBO, placebo; SE, standard error; W, Week.
Figure 2
Figure 2
Proportion of patients achieving symptomatic remission (all patients [A], non-bio-failed [B], and bio-failed [C]), stool frequency remission [all patients [D], non-bio-failed [E], and bio-failed [F]], and rectal bleeding remission (all patients [G], non-bio-failed [H], and bio-failed [I]) during LUCENT-1. Significance level is indicated for MIRI versus PBO at W1 to W12: *p < 0.05, ** p < 0.01, *** p ≤ 0.001. CI, confidence interval; IV, intravenous; MIRI, mirikizumab; N, number of patients; NRI, non-responder imputation; PBO, placebo; W, Week.
Figure 3
Figure 3
Proportion of patients achieving BU CMI (all patients [A], non-bio-failed [B], and bio-failed [C]) and BU remission (all patients [D], non-bio-failed [E], and bio-failed [F]) during LUCENT-1. BU CMI is defined as UNRS improvement of ≥ 3 points in patients with baseline UNRS ≥ 3. BU remission is defined as UNRS 0 or 1 in patients with baseline UNRS ≥ 3. Significance level is indicated for MIRI versus PBO at W1 to W12: *p < 0.05, **p < 0.01, ***p ≤ 0.001. BU, bowel urgency; CI, confidence interval; CMI, clinically meaningful improvement; IV, intravenous; MIRI, mirikizumab; N, number of patients; NR, non-responder imputation; PBO, placebo; Q4W, every 4 weeks; W, Week.
Figure 4
Figure 4
Proportion of patients achieving symptomatic remission (all patients [A], non-bio-failed [B], and bio-failed [C]), stool frequency remission (all patients [D], non-bio-failed [E], and bio-failed [F]), and rectal bleeding remission (all patients [G], non-bio-failed [H], and bio-failed [I]) during LUCENT-2. Significance level is indicated for MIRI versus PBO at W12 to W52: *p < 0.05, **p < 0.01, ***p ≤ 0.001. CI, confidence interval; MIRI, mirikizumab; N, number of patients; NRI, non-responder imputation; PBO, placebo; SC, subcutaneous; W, Week.
Figure 5
Figure 5
Proportion of patients achieving BU CMI (all patients [A], non-bio-failed [B], and bio-failed [C]) and BU remission (all patients [D], non-bio-failed [E], and bio-failed [F]) during LUCENT-2. BU CMI is defined as UNRS improvement of ≥ 3 points in patients with baseline UNRS ≥ 3. BU remission is defined as UNRS 0 or 1 in patients with baseline UNRS ≥ 3. Significance level is indicated for MIRI versus PBO at W12 to W52: *p < 0.05, **p < 0.01, ***p ≤ 0.001. BU, bowel urgency; CI, confidence interval; CMI, clinically meaningful improvement; IV, intravenous; MIRI, mirikizumab; N, number of patients; NRI, non-responder imputation; PBO, placebo; SC, subcutaneous; W, Week.
Figure 6
Figure 6
Proportion of patients achieving abdominal pain improvement (all patients [A], non-bio-failed [B], and bio-failed [C]) and change from baseline in Fatigue NRS LSM [SE] (all patients [D], non-bio-failed [E], and bio-failed [F]) during LUCENT-2. Significance level is indicated for MIRI versus PBO at W12 to W52: *p < 0.05, **p < 0.01, ***p ≤ 0.001. BL, baseline; CI, confidence interval; IV, intravenous; LSM, least squares mean; MIRI, mirikizumab; N, number of patients; NRI, non-responder imputation; NRS, numerical rating scale; PBO, placebo; SC, subcutaneous; SE, standard error; W, Week.
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