Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study
Open accessAbstract
Background The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. Methods In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia. Eligible patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least 3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) of at least 7 (≥4 for patients with isolated ileitis) on ileocolonoscopy scored by a masked central reader. Patients were randomised 1:1:1 using an interactive response system to a double-blind investigational product, and stratified by previous exposure to TNF antagonists (yes vs no). Patients received intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4, and 8. The primary outcome was clinical remission (CDAI <150) at week 12 (intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02031276. Findings Between March, 2014, and September, 2015, 213 patients were screened, and 121 patients randomised. At baseline, 113 patients (93%) had been previously treated with at least one tumour necrosis factor (TNF) antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82 risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg arms) had clinical remission versus six (15%) of 39 placebo patients (difference vs placebo 15·0%, 95% CI 0·1 to 30·1; p=0·0489). Ten (24%) of 41 patients who received 200 mg risankizumab had clinical remission (9·0%, -8·3 to 26·2; p=0·31) and 15 (37%) of 41 who received the 600 mg dose (20·9%, 2·6 to 39·2; p=0·0252). 95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to 200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse events (nine, six, three); 12 discontinued (six, five, one); 24 had serious adverse events (12, nine, three). The most common adverse event was nausea and most common serious adverse event was worsening of underlying Crohn's disease. No deaths occurred. Interpretation In this short-term study, risankizumab was more effective than placebo for inducing clinical remission in patients with active Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition of p19 might be a viable therapeutic approach in Crohn's disease. Funding Boehringer Ingelheim.
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Targan, S. R., Hanauer, S. B., van Deventer, S. J. H., Mayer, L., Present, D. H., Braakman, T., DeWoody, K. L., Schaible, T. F., & Rutgeerts, P. J. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710093371502 · Cited by 3,135 · see citing works
A Genome-Wide Association Study Identifies <i>IL23R</i> as an Inflammatory Bowel Disease Gene
Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., Steinhart, A. H., Abraham, C., Regueiro, M., Griffiths, A., et al. (2006) · Science · doi:10.1126/science.1135245 · Cited by 3,039 · see citing works
Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease
Sandborn, W. J., Feagan, B. G., Rutgeerts, P. J., Hanauer, S. B., Colombel, J., Sands, B. E., Lukáš, M., Fedorak, R. N., Lee, S., Bressler, B. L., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215739 · Cited by 2,716 · see citing works
Self-citationBaumgart, D. C., & Sandborn, W. J. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60026-9 · Cited by 2,205 · see citing works
Self-citationUstekinumab as Induction and Maintenance Therapy for Crohn’s Disease
Feagan, B. G., Sandborn, W. J., Gasink, C., Jacobstein, D., Lang, Y., Friedman, J. R., BLANK, M. A., Johanns, J., Gao, L.-L., Ye, M., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1602773 · Cited by 1,851 · see citing works
Self-citationHanauer, S. B., Sandborn, W. J., Rutgeerts, P. J., Fedorak, R. N., Lukáš, M., MacIntosh, D. G., Panaccione, R., Wolf, D. C., & Pollack, P. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.030 · Cited by 1,711 · see citing works
Self-citationHueber, W., Sands, B. E., Lewitzky, S., Vandemeulebroecke, M., Reinisch, W., Higgins, P. D. R., Wehkamp, J., Feagan, B. G., Yao, M. D., Karczewski, M., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301668 · Cited by 1,547 · see citing works
Self-citationAntitumor and antimetastatic activity of interleukin 12 against murine tumors.
Brunda, M. J., Luistro, L. L., Warrier, R. R., Wright, R. B., Hubbard, B. R., Murphy, M. E., Wolf, S. F., & Gately, M. K. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.4.1223 · Cited by 1,197 · see citing works
Certolizumab Pegol for the Treatment of Crohn's Disease
Sandborn, W. J., Feagan, B. G., Stoinov, S., Honiball, P., Rutgeerts, P. J., Mason, D. H., Bloomfield, R., & Schreiber, S. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067594 · Cited by 1,141 · see citing works
Self-citationUstekinumab Induction and Maintenance Therapy in Refractory Crohn's Disease
Sandborn, W. J., Gasink, C., Gao, L.-L., BLANK, M. A., Johanns, J., Guzzo, C. A., Sands, B. E., Hanauer, S. B., Targan, S. R., Rutgeerts, P. J., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203572 · Cited by 1,132 · see citing works
Self-citationIrvine, E. J., Feagan, B. G., Rochon, J., Archambault, A., Fedorak, R. N., Groll, A., Kinnear, D. G., Saibil, F. G., & McDonald, J. W. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90585-1 · Cited by 709 · see citing works
Self-citationIL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease
Geremia, A., Arancibia-Cárcamo, C. V., Fleming, M. P. P., Rust, N. A., Singh, B., Mortensen, N., Travis, S. P. L., & Powrie, F. M. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101712 · Cited by 640 · see citing works
Natalizumab for the Treatment of Active Crohn’s Disease: Results of the ENCORE Trial
Targan, S. R., Feagan, B. G., Fedorak, R. N., Lashner, B. A., Panaccione, R., Present, D. H., Spehlmann, M. E., Rutgeerts, P. J., Tulassay, Z., Volfová, M., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.024 · Cited by 614 · see citing works
Self-citationRutgeerts, P. J., Assche, G. V., Sandborn, W. J., Wolf, D. C., Geboes, K. J., Colombel, J., Reinisch, W., Kumar, A., Lazar, A., Camez, A. A., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.01.035 · Cited by 577 · see citing works
Self-citationPeyrin‐Biroulet, L., Deltenre, P., de Suray, N., Branche, J., Sandborn, W. J., & Colombel, J. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.03.014 · Cited by 576 · see citing works
Self-citationPeyrin‐Biroulet, L., Reinisch, W., Colombel, J., Mantzaris, G. J., Kornbluth, A. A., Diamond, R. H., Rutgeerts, P. J., Tang, L., Cornillie, F. J., & Sandborn, W. J. (2013) · Gut · doi:10.1136/gutjnl-2013-304984 · Cited by 501 · see citing works
Self-citationCirculating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation
Kleinschek, M. A., Boniface, K., Sadekova, S., Grein, J., Murphy, E. E., Turner, S. P., Raskin, L., Desai, B., Faubion, W. A., de Waal Malefyt, R., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081712 · Cited by 460 · see citing works
Brandse, J. F., BRINK, G. R. V. D., Wildenberg, M. E., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.016 · Cited by 434 · see citing works
Targan, S. R., Feagan, B., Vermeire, S., Panaccione, R., Melmed, G. Y., Landers, C., Li, D., Russell, C., Newmark, R., Zhang, N., et al. (2016) · American Journal of Gastroenterology · doi:10.1038/ajg.2016.298 · Cited by 383 · see citing works
Self-citationLichtenstein, G. R., Sbreu, M. T., Cohen, R. D., & Tremaine, W. J. (2006) · PubMed · Cited by 370 · see citing works
Gisbert, J. P., Marín, A. C., McNicholl, A. G., & Chaparro, M. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13083 · Cited by 321 · see citing works
Dassopoulos, T., Sultan, S., Falck-Ytter, Y. T., Inadomi, J. M., & Hanauer, S. B. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.10.046 · Cited by 297 · see citing works
Krueger, J. G., Ferris, L. K., Menter, A., Wagner, F. D., White, A., Visvanathan, S., Lalovic, B. B., Aslanyan, S., Wang, E. E. L., Hall, D., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.01.018 · Cited by 255 · see citing works
Self-citationIL-23: a master regulator in Crohn disease
Neurath, M. F. (2007) · Nature Medicine · doi:10.1038/nm0107-26 · Cited by 238 · see citing works
Self-citationTerdiman, J. P., Gruss, C. B., Heidelbaugh, J. J., Sultan, S., & Falck-Ytter, Y. T. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.10.047 · Cited by 221 · see citing works
Converging goals of treatment of inflammatory bowel disease from clinical trials and practice
Levesque, B. G., Sandborn, W. J., Ruel, J., Feagan, B. G., Sands, B. E., & Colombel, J.-F. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.08.003 · Cited by 217 · see citing works
Self-citationTherapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Inflammatory Bowel Disease
Ordás, Í., Feagan, B. G., & Sandborn, W. J. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.06.032 · Cited by 211 · see citing works
Self-citationStobie, L., Gurunathan, S., Prussin, C., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160197797 · Cited by 196 · see citing works
IOIBD technical review on endoscopic indices for Crohn's disease clinical trials
Vuitton, L., Marteau, P. R., Sandborn, W. J., Levesque, B. G., Feagan, B. G., Vermeire, S., Danese, S., D’Haens, G., Löwenberg, M., Khanna, R., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309903 · Cited by 196 · see citing works
Self-citationCampa, M., Mansouri, B., Warren, R. B., & Menter, A. (2015) · Dermatology and Therapy · doi:10.1007/s13555-015-0092-3 · Cited by 143 · see citing works
Singh, S., Kroe‐Barrett, R., Canada, K. A., Zhu, X., Sepulveda, E., Wu, H. H., Ya-qin, H., Raymond, E. L., Ahlberg, J., Frego, L., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1032491 · Cited by 122 · see citing works
van Schie, K. A., Wolbink, G., & Rispens, T. (2015) · mAbs · doi:10.1080/19420862.2015.1048411 · Cited by 117 · see citing works
Khanna, R., Bouguen, G., Feagan, B. G., D’Haens, G., Sandborn, W. J., Dubcenco, E., Baker, K. A., & Levesque, B. G. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000131 · Cited by 79 · see citing works
Self-citationGordon, J. P., McEwan, P. C., Maguire, A., et al. (2015) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000000378 · Cited by 55 · see citing works
Matsuoka, K., & Kanai∥, T. (2013) · Digestion · doi:10.1159/000351386 · Cited by 8 · see citing works
(2016) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2016.02.1058 · Cited by 2 · see citing works
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- Authors
- Feagan, B. G., Sandborn, W. J., D'Haens, G., Panés, J., Kaser, A., Ferrante, M., Louis, E., Franchimont, D., Dewit, O., Seidler, U., Kim, K.-J., Neurath, M. F., Schreiber, S., Scholl, P., Pamulapati, C., Lalovic, B., Visvanathan, S., Padula, S. J., Herichova, I., Soaita, A., Hall, D. B., & Böcher, W. O.
- Affiliations
- Western University (CA)
- UC San Diego Health System (US)
- Hospital Clínic de Barcelona (ES)
- University of Cambridge (GB)
- Universitair Ziekenhuis Leuven (BE)
- Centre Hospitalier Universitaire de Liège (BE)
- Erasmus Hospital (BE)
- Cliniques Universitaires Saint-Luc (BE)
- Medizinische Hochschule Hannover (DE)
- Asan Medical Center (KR)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Boehringer Ingelheim (United States) (US)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (Austria) (AT)
- Corresponding author
- Feagan, Brian G
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 389
- Issue
- 10080
- Pages
- 1699-1709
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2606398981
- Cited by
- 451
- References
- 36
- Citations by year
- 2026: 20 · 2025: 35 · 2024: 35 · 2023: 42 · 2022: 49 · 2021: 50 · 2020: 51 · 2019: 73 · 2018: 72 · 2017: 23
- FWCI
- 39.75
- Type
- journal article
- Language
- en
- Open access
- green
- orbi.uliege.be
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- risankizumab, interleukin-23 inhibition, Crohn's disease, induction therapy, monoclonal antibodies, clinical remission, CDAI, Crohn's Disease Endoscopic Index of Severity, adverse events, drug safety, anti-drug antibodies, immunogenicity, immunosuppression
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Monoclonal, Crohn Disease, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Gastrointestinal Agents, Humans, Male, Middle Aged, Remission Induction, Severity of Illness Index, Treatment Outcome, Interleukin-23 Subunit p19, Young Adult
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