Positioning risankizumab in the treatment algorithm of moderate-to-severe Crohn's disease

Abstract

Risankizumab is a humanized monoclonal antibody that inhibits the p19 subunit of IL-23 cytokine. Recently it has been approved for the treatment of patients with moderate-to-severe Crohn's disease (CD). We conducted a scoping review to summarize the available data on risankizumab and to define its positioning in the treatment algorithm of CD. Pubmed, Embase and Scopus databases were searched up to Oct 31, 2023 to identify studies reporting efficacy and safety data of risankizumab in patients with CD. Risankizumab is an effective and safe drug for the management of patients with moderate-to-severe CD. It could be used as first-line therapy in biologic-naive patients and in patients who have previously failed other biological therapies.

Plain language summary

When we eat the food is processed and absorbed by the gastrointestinal tract. Sometimes, in some people, the gastrointestinal tract gets inflamed, causing problems like tummy ache and diarrhea: this condition is called Crohn's disease. To help turn off this inflammation and make people with Crohn's disease feel better, there's a new treatment called risankizumab. Risankizumab binds to the proteins in the body that cause inflammation and blocks their effects. This helps to reduce gastrointestinal inflammation and relieve its symptoms. Scientific studies have shown that is effective, safe, and it starts working quickly. Patients using this treatment do not have to go to the hospital every time. After three times in the outpatient's clinic, they can continue the treatment comfortably at home using a small device that sticks to the body and administers the medicine.

Executive summary

Crohn's disease & its therapy

• Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD), an immune-mediated condition affecting the entire GI tract from the mouth to the anus.

• The advent of biologic drugs revolutionized the treatment of CD; nevertheless 30–40% of patients do not respond to initial biological therapy and up to 50% lose response over time.

• It appears urgent to find new therapeutic targets.

About risankizumab

• Risankizumab is a humanized IgG1 monoclonal antibody that inhibits the p19 subunit of the cytokine IL-23, recently approved by the FDA & EMA for CD.

Phase III trials

• In the Phase III induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials risankizumab demonstrated both effectiveness and safety in the treatment of moderate-to-severe CD.

Strenghs of risankizumab

• Main strengths of risankizumab include its efficacy for both biologic – naive and biologic – experienced patients, its safety, the subcutaneous self-home-administration in the maintenance phase, a rapid mechanism of action and a low immunogenicity.

Conclusion

• Based on the available data, risankizumab could play a crucial role in the treatment of patients with CD.

Keywords: :

• biological therapy
• Crohn's disease
• IBD
• IL-23 inhibitor
• inflammatory bowel disease
• risankizumab

Author contributions

S Danese conceived the study. F Lusetti and F D'Amico wrote the manuscript and created the images and tables. S Danese, M Allocca, F Furfaro, G Fiorino, TL Parigi, S Radice, L Peyrin-Biroulet and A Zilli revised the manuscript. All the authors approved the final version of the manuscript.

Financial disclosure

The authors have no 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.

Competing interests disclosure

F Lusetti declares no conflict of interest. F D'Amico has served as a speaker for Sandoz, Janssen, Galapagos and Omega Pharma; he has also served as advisory board member for Ferring, Galapagos, Abbvie and Nestlè. M Al-locca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie and Pfizer. F Furfaro received consulting fees from Amgen and Abbvie and lecture fees from Janssen and Pfizer. A Zilli declares no conflict of interest. G Fiorino received consultancy fees from Fer-ring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. TL Parigi declares no conflict of interest. S Radice declares no conflict of interest. L Peyrin-Biroulet declares consulting fees from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Fer-ring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Im-age Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Til-lots, Viatris, Vifor, Ysopia, Abivax; he also declares grants from Takeda, F Kabi, Celltri-on; he also has served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac. S Danese has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Fer-ring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

We thank FIRMAD for the support of the manuscript.