Risankizumab Tops Competitor for Clinical Remission in Moderate-to-Severe CD

SAN FRANCISCO — More adults with moderate-to-severe Crohn’s disease (CD) reached clinical remission after 6 months on risankizumab (Skyrizi) versus ustekinumab (Stelara), according to a head-to-head trial.

In the phase III study, 59% of patients (n=255) receiving risankizumab (Skyrizi) achieved clinical remission after 24 weeks of therapy compared to 40% of patients (n=265) receiving ustekinumab, based on a Clinical Disease Activity Index (CDAI) score of >150 points, reported Jessica R. Allegretti, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

Risankizumab met the non-inferiority margin of 10% when compared to ustekinumab, along with the superiority endpoint, with 32% of risankizumab patients and 16% of ustekinumab patients achieving endoscopic remission at week 48 (P<0.0001). Endoscopic remission was defined as a Simple Endoscopic Score (SES-CD) of ≤4 and at least a 2-point reduction in SES-CD from baseline, with no subscore >1.

“This is a part-time biologic option for moderate-to-severe Crohn’s disease” with “really great endoscopic control, visible mucosal improvement with endoscopic response, durable disease control, and clinical remission as early as week 12,” Allegretti said in a presentation at the Crohn’s and Colitis Congress.

SEQUENCE data were presented at the 2023 United European Gastroenterology meeting and published in 2024 in the New England Journal of Medicine. The trial has an estimated study completion date of February 2028. Risankizumab was FDA approved in 2022 for adults with moderate-to-severe CD, as was ustekinumab in 2016.

Erin Lamba, NP, of Cedars-Sinai in Los Angeles, said she was not surprised by the findings as they matched what she has seen in clinical practice. However, the results are important for maintaining patient access to risankizumab.

“Anytime there’s a head-to-head trial between two drugs, it’s very useful for clinical practice, and positioning drugs against each other, and talking to patients about why we might choose one drug over another,” Lamba told MedPage Today. Such data can be used to show efficacy for insurance coverage, Lamba said, and Susie Lee, MP, also of Cedars-Sinai, agreed, noting that “at the end of the day, the insurance company has to approve it, so we have to show data for why we’re saying they [need this drug].” Neither Lee nor Lamba were involved in the study.

SEQUENCE trial patients were randomly assigned to receive risankizumab or ustekinumab for 48 weeks. All participants had demonstrated intolerance or an inadequate response to at least one anti-TNF therapy. Inadequate response was defined as signs and symptoms of persistently active disease despite at least one induction regimen of infliximab, adalimumab (Humira), or certolizumab peg (Cimzia), or as recurrence of symptoms during maintenance dosing after previous clinical benefit from one of these agents.

The groups were not significantly different in disease duration (mean of about 9 years), average CDAI score, SES-CD, median fecal calprotectin, median high-sensitivity CRP, stool frequency, abdominal pain score, immunomodulator use, steroid use, and number of prior failed anti-TNF therapies.

During an 8-week induction with a mandatory steroid taper, the risankizumab group received three 600 mg IV doses at weeks 0, 4, and 8, and the ustekinumab group received a weight-based dose at week 0. Those who could not tolerate the steroid taper could have their corticosteroid dose increased at the investigator’s discretion up to their baseline dose. The groups then received either 360 mg of subcutaneous risankizumab or 90 mg of subcutaneous ustekinumab every 8 weeks.

Risankizumab also showed superiority compared to ustekinumab in all secondary endpoints: Clinical remission at 48 weeks occurred in 61% of risankizumab patients and 41% of ustekinumab patients (P<0.0001). However, the open-label nature of the trial may have influenced these results.

Endoscopic response, defined as >50% decrease in SES-CD from baseline, occurred in 45% of risankizumab patients at both 24 and 48 weeks, compared to 26% of ustekinumab patients at 24 weeks and 22% at 48 weeks (P<0.0001). Nearly a third (31%) of those taking risankizumab achieved steroid-free endoscopic remission at week 48 compared to 16% of those taking ustekinumab (P<0.0001).

“The safety profile of Skyrizi was generally consistent with what was previously reported in all of the other previous trials and described in the prescribing information, so no new safety signals were elucidated in this,” Allegretti said.

Rates of overall adverse events (AEs), serious AEs, and treatment-emergent AEs were not significantly different between the groups. No serious hypersensitivity events occurred, and infections occurred in 53.8% of risankizumab participants and 44.5% of ustekinumab patients. Rates of discontinuation due to AEs were 3.8% and 4.9%, respectively.

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