Risankizumab Subcutaneous Induction for Crohn’s Disease: Insights From the AFFIRM Trial, With Millie Long, MD, MPH

New data from the AFFIRM trial suggest that a fully subcutaneous induction strategy with risankizumab (Skyrizi) may deliver strong efficacy while offering a more convenient treatment pathway for patients with Crohn’s disease, adding to the growing body of evidence supporting IL-23 inhibition in this patient population.

First approved for Crohn’s disease in 2022, risankizumab has historically required intravenous induction before transitioning to subcutaneous maintenance dosing. In an interview discussing the AFFIRM results, lead investigator Millie Long, MD, MPH, chief of the division of gastroenterology and hepatology at the University of North Carolina, Chapel Hill noted that evaluating a subcutaneous induction approach represents an important step toward making effective therapy more accessible.

“Previously, risankizumab had been incredibly promising,” Long told HCPLive. “This is obviously an approved agent, but it required IV induction, and so now allowing for a very effective therapy in a subcutaneous load allows us to reach more patients and to potentially get drug in the hands of patients quicker in terms of not having to wait for infusion center chairs, and hopefully will allow us to improve outcomes for those patients.”

The global, phase 3, randomized, placebo-controlled, double-blind AFFIRM study assessed the efficacy and safety of risankizumab SC as an induction treatment in adult patients with moderately to severely active Crohn's disease, with co-primary endpoints of percentage of participants with CDAI Clinical Remission (CDAI < 150) and percentage of participants with endoscopic response at week 12.

“In any induction clinical trial, we look at co primary endpoints, meaning we want to make sure that patients are feeling better in terms of clinical remission, but we also want to make sure that there is an endoscopic response, meaning that the actual inflammation visualized at the level of the endoscopy is improving,” Long explained.

In AFFIRM, a total of 289 patients were randomly assigned in a 2:1 ratio to risankizumab SC or placebo. Results showed significantly greater proportions of patients treated with risankizumab SC induction achieved CDAI clinical remission (55% vs 30%; P <.0001) and endoscopic response (44% vs 14%; P <.0001) at week 12 compared to placebo. Among patients with clinical response after 12 weeks of risankizumab SC induction treatment followed by 12 weeks of maintenance, 67% achieved CDAI clinical remission at week 24 and 57% achieved endoscopic response at week 24.

Long called attention to results in the advanced therapy-naïve population of the study, noting those treated with subcutaneous risankizumab achieved a 73.1% clinical remission rate and a 61.2% endoscopic response rate. She additionally cited encouraging results in patients with prior advanced therapy failure, further supporting risankizumab’s efficacy across patient populations. However, with the particularly strong results in biologic-naïve patients, Long suggests it may have potential as a first-line advanced therapy option in Crohn’s disease.

During the 12-week, double-blind, placebo-controlled period, the safety profile of risankizumab SC was consistent with the safety profile observed in Crohn's disease with no new safety risks observed.

Although the AFFIRM trial focused on a 12-week induction period, Long emphasized that durability and long-term safety data for risankizumab are supported by the broader clinical program evaluating the therapy and the IL-23 inhibitor class.

“The entire risankizumab portfolio and program now has many years of use and that's where the safety data really shine, that this is a highly effective, very safe drug where we're not seeing significant adverse effects in terms of infectious complications, we're not seeing malignancy risks, and really that long term data are what is so reassuring for the risankizumab portfolio,” Long said.

Editors’ Note: Long reports relevant disclosures with AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Intercept, Janssen, Pfizer, Prometheus, Roivant, Sanofi, Takeda, and Target RWE.

References

1. Brooks A. AFFIRM: Risankizumab (Skyrizi) Subcutaneous Induction Achieves Primary Endpoints in Crohn’s Disease. HCPLive. March 2, 2026. Accessed March 11, 2026. https://www.hcplive.com/view/affirm-risankizumab-skyrizi-subcutaneous-induction-achieves-primary-endpoints-in-crohn-s-disease

2. Walter, K. FDA Approves Risankizumab For Crohn’s Disease. HCPLive. June 17, 2022. Accessed March 11, 2026. https://www.hcplive.com/view/fda-appropves-risankizumab-crohns-disease