ABSTRACT
Introduction: Medical therapy for Crohn’s disease (CD) is directed at controlling intestinal inflammation to prevent development of disease-related complications. Not all patients will respond to currently available treatments and thus, novel therapies are needed. The interleukin (IL)-23 cytokine axis is implicated in CD pathogenesis and so targeting this pathway has become an important focus for drug development.
Areas covered: This review summarizes the role of the IL23 cytokine pathway in CD pathogenesis and appraises phase I and II clinical trial data for novel IL23p19 specific monoclonal antibodies for the treatment of CD. The evidence for risankizumab (BI655066/ABBV066), brazikumab (MEDI2070, formerly AMG139), guselkumab (CNTO1959), tildrakizumab (MK3222), and mirikizumab (LY3074828) is reviewed; moreover, future applications for these agents are considered.
Expert opinion: Targeting the specific p19 subunit of IL23 is a promising strategy in CD. Two multicenter, randomized, placebo-controlled phase II clinical trials have evaluated risankizumab and brazikumab. Both studies indicate that IL23-specific blockade is likely to be a safe and effective alternative to current biologics, including the TNF antagonists vedolizumab and ustekinumab. Confirmatory Phase 3 studies are underway. Ultimately, comparative effectiveness trials will be necessary to define the role of IL23-specific antagonists in CD treatment algorithms.
Declaration of interest
V. Jairath has received consulting fees from AbbVie, Sandoz, Takeda, Janssen, Robarts Clinical Trials and speakers’ bureau fees from Takeda, Janssen, Shire, Ferring.
R. Khanna has received scientific advisory board fees from AbbVie, Janssen, Pfizer, Takeda; consulting fees from AbbVie, Janssen, Takeda, Robarts Clinical Trials and payments for lectures/speakers’ bureau fees from AbbVie, Janssen, Shire, and Takeda.
B. Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma and speaker’s fees from UCB, AbbVie, and J&J/Janssen.
Note: Robarts Clinical Trials began in 1986 as an academic research unit within the Robarts Research Institute which is affiliated with University Hospital and Western University. A subsequent international (United States of America and Netherlands) expansion in 2012 necessitated establishment of a corporate entity to meet international federal/taxation regulations. All profits from Robarts Clinical Trials, Inc. are directed toward academic research. None of the authors with affiliation to Robarts Clinical Trials, Inc. have an equity position or any shares in the corporation. Robarts Clinical Trials provides central endoscopy and histology reading as a commercial service. Affiliated authors have not received specific individual research support from Robarts Clinical Trials.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
One peer reviewer has served as an advisor and speaker and has received research support from Abbvie, Allergan, Eli Lily, and Merck.
Other peer reviewers on this manuscript have no relevant financial or other relationships to disclose