Abstract
Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226
| Original language | English |
|---|---|
| Pages (from-to) | 495-508 |
| Number of pages | 14 |
| Journal | Gastroenterology |
| Volume | 162 |
| Issue number | 2 |
| Early online date | 2021 |
| DOIs | |
| Publication status | Published - Feb 2022 |
Keywords
- Cytokine
- IBD
- Inhibitor
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In: Gastroenterology, Vol. 162, No. 2, 02.2022, p. 495-508.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease
AU - Sands, Bruce E.
AU - Peyrin-Biroulet, Laurent
AU - Kierkus, Jaroslaw
AU - Higgins, Peter D. R.
AU - Fischer, Monika
AU - Jairath, Vipul
AU - Hirai, Fumihito
AU - D'Haens, Geert
AU - Belin, Ruth M.
AU - Miller, Debra
AU - Gomez-Valderas, Elisa
AU - Naegeli, April N.
AU - Tuttle, Jay L.
AU - Pollack, Paul F.
AU - Sandborn, William J.
N1 - Funding Information: The authors would like to thank Linden Green for providing writing and editorial support, Catherine Milch for providing medical peer review, Lai Shan Chan for providing analytical support, and Zhantao Lin for providing statistical review. Bruce E. Sands, MD (Data curation: Supporting; Investigation: Lead; Methodology: Equal; Writing – review & editing: Lead). Laurent Peyrin-Biroulet, MD, PhD (Data curation: Supporting; Resources: Supporting; Writing – review & editing: Supporting). Jaroslaw Kierkus, MD, PhD (Data curation: Supporting; Resources: Supporting; Writing – review & editing: Supporting). Peter D.R. Higgins, MD, PhD (Data curation: Supporting; Resources: Equal; Writing – review & editing: Supporting). Monika Fischer, MD (Data curation: Supporting; Investigation: Equal; Resources: Supporting; Writing – review & editing: Supporting). Vipul Jairath, MD, PhD (Data curation: Equal; Resources: Supporting; Writing – review & editing: Supporting). Fumihito Hirai, MD (Data curation: Equal; Investigation: Supporting; Resources: Equal; Writing – review & editing: Supporting). Geert D'Haens, MD, PhD (Data curation: Equal; Resources: Equal; Writing – review & editing: Supporting). Ruth M. Belin, MD (Formal analysis: Equal; Investigation: Equal; Writing – review & editing: Supporting). Debra Miller, PhD (Formal analysis: Equal; Writing – review & editing: Supporting). Elisa Gomez-Valderas, MS (Conceptualization: Equal; Data curation: Equal; Formal analysis: Lead; Investigation: Equal; Methodology: Equal; Validation: Lead; Writing – review & editing: Equal). April N. Naegeli, DrPH, MPH (Investigation: Supporting; Writing – review & editing: Supporting). Jay L. Tuttle, PhD (Conceptualization: Equal; Formal analysis: Supporting; Investigation: Supporting; Methodology: Equal; Writing – review & editing: Supporting). Paul F. Pollack, MD (Conceptualization: Lead; Formal analysis: Equal; Investigation: Equal; Methodology: Equal; Writing – review & editing: Lead). William J. Sandborn, MD (Conceptualization: Equal; Data curation: Equal; Investigation: Equal; Resources: Equal; Writing – review & editing: Supporting). Conflicts of interest B.E.S. reports the following: research grants from Celgene, Janssen, Takeda, Pfizer, and Theravance Biopharma R&D; and consulting fees from 4D Pharma, Abbvie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Bacainn Therapeutics, Boehringer-Ingelheim, Boston Pharmaceuticals, Capella Bioscience, Celgene, Celltrion Healthcare, F.Hoffmann-La Roche, Ferring, Gilead, Immunic, Index Pharmaceuticals, Ironwood Pharmaceuticals, Janssen, Lilly, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Redhill Biopharma, Rheos Medicines, Salix Pharmaceuticals, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Surrozen, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, USWM Enterprises, Viela Bio, and Vivelix Pharmaceuticals. W.J.S. reports the following: research grants from Abbvie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, Theravance Biopharma; consulting fees from Abbvie, Abivax, Admirx, Alfasigma, Alimentiv (Robarts Clinical Trials, owned by Health Academic Research Trust [HART]), Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Meyers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Progenity, Shoreline Biosciences, Ventyx Biosciences, and Vimalan Biosciences. W.J.S.: Iveric Bio - consultant, stock options; Progenity - stock; Oppilan Pharma - consultant, stock options; Prometheus Biosciences - employee, stock options; Ventyx Biosciences – stock options; Vimalan Biosciences – stock options. V.J. reports the following: consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Pfizer, Fresenius Kabi, Bristol Myers Squibb, Roche, Ferring, Sandoz, Merck, Takeda, Janssen, Alimentiv Inc (formerly Robarts Clinical Trials), Topivert, Celltrion, and Mylan; and speaker's fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer. M.F. reports the following: consulting fees from Eli Lilly, Abbvie, Janssen, Takeda, and Bristol Myers Squibb. D.M., E.G.V., J.L.T., R.B., A.N.N., and P.F.P. are current employees and shareholders of Eli Lilly and Company. J.K. reports the following: consulting fees from Eli Lilly, Abbvie, and Nestle. F.H. reports the following: research grants from Eli Lilly, AbbVie, EA Pharma, JIMRO, Ayumi, Kissei, Mochida, Eisai, and Asahi Kasei Medical; consulting fees from Kissei; and speaker's fees from AbbVie, EA Pharma, Janssen, Mochida, Mitsubishi Tanabe, and Takeda. G.D. reports the following: advisor for AbbVie, Ablynx, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion, Cosmo, Dr Falk Pharma, Echo Pharmaceuticals, Eli Lilly and Company, Engene, Ferring, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Kintai Therapeutics, Lycera, Medimetrics, Medtronics, Merck Sharp Dome, Millenium/Takeda, Mitsubishi Pharma, Mundipharma, Nextbiotics, Novo Nordisk, Otsuka, Pfizer/Hospira, Photopill, Prodigest, Progenity, Prometheus Laboratories/Nestle, Protagonist, RedHill, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor. P.D.R.H. reports the following: consultancy and/or advisory board fees from Abbvie, Eli Lilly and Company, and Takeda; and honoraria from Takeda. L.P.B. reports the following: personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance; grants from Abbvie, MSD, and Takeda; and stock options from CTMA. Funding This study was funded by Eli Lilly and Company. Funding Information: Funding This study was funded by Eli Lilly and Company. Publisher Copyright: © 2022
PY - 2022/2
Y1 - 2022/2
N2 - Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226
AB - Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226
KW - Cytokine
KW - IBD
KW - Inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85121987774&partnerID=8YFLogxK
U2 - https://doi.org/10.1053/j.gastro.2021.10.050
DO - https://doi.org/10.1053/j.gastro.2021.10.050
M3 - Article
C2 - 34748774
SN - 0016-5085
VL - 162
SP - 495
EP - 508
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -