Risankizumab-rzaa is the first and only specific IL-23 inhibitor approved for the treatment of moderately to severely active Crohn’s disease in adults.
In June 2022, the FDA approved a third indication for risankizumab-rzaa (Skyrizi), a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-23 through inhibition of its p19 subunit, for the treatment of moderately to severely active disease of Crohn’s in adults.1 Because there is no cure for Crohn’s disease, it remains a lifelong condition with limited treatments available.
To date, risankizumab-rzaa is the first and only specific IL-23 inhibitor to treat this indication. In the past 2 years, it received 2 FDA approvals for moderate to severe plaque psoriasis and active psoriatic arthritis in adults.1 ADVANCE, MOTIVATE and FORTIFY are Phase 3 studies supporting this new Crohn’s disease indication for risankizumab-rzaa.
The ADVANCE and MOTIVATE studies were multicenter, randomized, double-blind, placebo-controlled Phase 3 induction studies designed over a 12-week period. These studies evaluated the safety and efficacy of risankizumab-rzaa at doses of 600 mg and 1200 mg compared to placebo in adults with moderate to severe Crohn’s disease.2
These studies included biologically naive patients or patients who were either intolerant or had an inadequate response to biological therapy.2 In addition, these are the first studies to identify co-primary endpoints defined by both the CD Activity Index (CDAI) and endoscopic response results.
ADVANCE and MOTIVATE, randomized patients to receive intravenous (IV) risankizumab-rzaa (600 mg or 1200 mg) or placebo at weeks 0, 4 and 8. rzaa and 42% at 1200 mg risankizumab-rzaa vs. 25% with placebo.2
Similarly, doses of 600 mg, 1200 mg, and placebo in MOTIVATE yielded clinical CDAI remission rates of 42%, 40%, and 20%, respectively.2 In both studies, the results regarding both the 600 mg and 1200 mg doses were statistically significantly better compared to placebo.
The 1200 mg risankizumab-rzaa provided no additional benefit at week 12 and is not recommended above 600 mg.3 During induction therapy, the most commonly reported adverse reactions (AEs) are upper respiratory tract infections, arthralgia, and headache.2
Overall, the incidence of AE was observed to be similar between both treatment groups in each study (table 1).2.3
In addition, the FORTIFY trial is a 52-week, multicenter, randomized, double-blind, double-blind, control-group maintenance study designed to evaluate the safety and efficacy of risankizumab-rzaa at doses of 180 mg and 360 mg compared to withdrawal symptoms in responsive patients from the ADVANCE and MOTIVATE studies (table 2).
These patients were re-randomized to receive 180 mg subcutaneously, 360 mg subcutaneously, or withdrawal symptoms (placebo) at week 12 and every 8 weeks ongoing.
In FORTIFY, the clinical remission rates of CDAI were 55% at 180 mg and 52% at 360 mg versus 41% at withdrawal. The 180 mg and 360 mg results reached statistical significance compared to placebo.
During maintenance therapy, the most common adverse reactions reported are injection site reactions, anemia, fever, abdominal pain, urinary tract infections, and arthropathy. Currently, FORTIFY is continuing as an open-label extension to evaluate the long-term safety of patients who have completed this study with an estimated completion date of June 9, 2026.4
Ultimately, these studies led to the FDA approval of risankizumab-rzaa for the treatment of moderately to severely active Crohn’s disease. Following this approval, patients with Crohn’s disease will be initiated on treatment with 600 mg infusion over at least 1 hour at weeks 0, 4 and 8.3
At Week 12 and every 8 weeks underway, patients will transition to a self-administered 360 mg subcutaneous injection via an on-body injector (Figure 1).3 The on-body injector was not used in the previously described experiments.
Uniquely, the ‘on-body’ injector delivers a dose in 5 minutes and thanks to the self-adhesive function and concealed needle, administration can be done hands-free.5 In addition, patients and caregivers have access to resources such as treatment affordability, nurse ambassadors, and insurance support through access specialists through a manufacturer-supported program.6
About the author
Jennifer N. Tovar, PharmD Candidate, University of Arizona Class of 2024
Teacher: Michelle Becker, PharmD, BCACP
- SKYRIZI® (risankizumab-rzaa) Receives FDA Approval as First and Only Specific Interleukin-23 (IL-23) for Treatment of Moderately to Severely Active Crohn’s Disease in Adults | AbbVie News Center. news.abbvie.com. Accessed July 8, 2022. https://news.abbvie.com/news/press-releases/skyrizi-risankizumab-rzaa-receives-fda-approval-as-first-and-only-specific-interleukin-23-il- 23-treatable-moderately-to-severe-active-crohn’s-disease-in-adults.htm
- D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results of the phase 3 ADVANCE and MOTIVATE induction studies. The Lancet. 2022;399(10340):2015-2030. doi:10.1016/s0140-6736(22)00467-6
- HIGHLIGHTS of PRESCRIPTION INFORMATION. https://www.rxabbvie.com/pdf/skyrizi_pi.pdf
- Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results of the multicenter, randomized, double-blind, placebo-controlled phase 3 FORTIFY maintenance trial with discontinuation. The Lancet. 2022;399(10340):2031-2046. doi:10.1016/s0140-6736(22)00466-4
- SKYRIZI® (risankizumab-rzaa) Dosage for Crohn’s Disease. www.skyrizi.com. Accessed July 13, 2022. https://www.skyrizi.com/crohns/about-skyrizi/dosing
- Visit SKYRIZI (risankizumab-rzaa). Skyrizi HCP. https://www.skyrizihcp.com/dermatology/support