Risankizumab-rzaa is the first and only specific IL-23 inhibitor approved to treat moderately to severely active Crohn 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 via inhibition of its p19 subunit, for treatment of moderately to severely active Crohn disease in adults.1 As there is no cure for Crohn disease, it remains a lifelong condition with limited available treatments.
To date, risankizumab-rzaa is the first and only specific IL-23 inhibitor to treat this indication. Within 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 trials that supported this new Crohn disease indication for risankizumab-rzaa.
The ADVANCE and MOTIVATE trials were multicenter, randomized, double-blind, placebo-controlled phase 3 induction studies designed over a 12-week period. These trials 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 disease.2
These studies included biologic naïve patients or those who were either intolerant or responded inadequately to biologic therapy.2 Additionally, these are the first trials to identify co-primary endpoints defined by both the CD Activity Index (CDAI) and endoscopic response results.
ADVANCE and MOTIVATE, randomly assigned patients to receive an intravenous (IV) risankizumab-rzaa (600 mg or 1200 mg) or placebo at weeks 0, 4, and 8. In ADVANCE, CDAI clinical remission rates yielded 45% at 600 mg risankizumab-rzaa and 42% at 1200 mg risankizumab-rzaa versus 25% with placebo.2
Similarly, in MOTIVATE, doses of 600 mg, 1200 mg, and placebo yielded rates for CDAI clinical remission of 42%, 40%, and 20%, respectively.2 In both trials, outcomes related to both the 600 mg and 1200 mg doses were statistically significantly better compared to placebo.
The 1200 mg risankizumab-rzaa did not produce any additional benefit by week 12 and is not recommended over 600 mg.3 During induction therapy, the most common adverse events (AEs) reported include upper respiratory infections, arthralgia, and headache.2
Overall AE incidences were observed to be similar among both treatment groups in each trial (Table 1).2,3
Additionally, the FORTIFY trial is a multicenter, randomized, double-blind, control group phase 3 maintenance study designed over a 52-week period to assess the safety and efficacy of risankizumab-rzaa at doses of 180 mg and 360 mg compared to withdrawal in responsive patients from the ADVANCE and MOTIVATE studies (Table 2).
These patients were re-randomized to receive subcutaneous 180 mg, subcutaneous 360 mg, or withdrawal (placebo) at week 12 and every 8 weeks ongoing.
In FORTIFY, CDAI clinical remission rates yielded 55% at 180 mg and 52% at 360 mg versus 41% with withdrawal. The 180 mg and 360 mg results reached statistical significance in comparison to placebo.
During maintenance therapy, the most common AEs reported include injection site reactions, anemia, pyrexia, abdominal pain, urinary tract infections, and arthropathy. Currently, FORTIFY continues as an open-label extension to evaluate the long-term safety of patients who completed this study with an estimated completion date of June 9, 2026.4
Ultimately, these trials led to the FDA approval of risankizumab-rzaa to treat moderately to severely active Crohn disease. Following this approval, patients with Crohn disease will be initiated treatment with 600 mg infusion for at least 1 hour at weeks 0, 4, and 8.3
At week 12 and every 8 weeks ongoing, patients will transition to self-administered 360mg subcutaneous injection via an on-body injector (Figure 1).3 In the previous trials described, the on-body injector was not used.
Uniquely, the on-body injector administers dose delivery in 5 minutes and its adhesive feature and hidden needle allows delivery to be hands-free.5 Additionally, patients and health care providers have access to resources such as treatment affordability, nurse ambassadors, and insurance support via access specialists through a manufacturer-supported program.6
About the Author
Jennifer N. Tovar, PharmD Candidate, University of Arizona Class of 2024
Preceptor: Michelle Becker, PharmD, BCACP