How Head-to-Head SEQUENCE Data Shape Crohn’s Disease Treatment Decisions, With Raja Atreya, MD

New long-term data from the SEQUENCE program, presented at the 2026 Congress of the European Crohn’s and Colitis Organisation (ECCO), continue to reinforce the clinical impact of risankizumab (Skyrizi) in moderate-to-severe Crohn’s disease, particularly among patients with prior anti-TNF failure.

In discussing the findings, Raja Atreya, MD, head of the IBD Center at University Hospital of Erlangen, characterized SEQUENCE as a “landmark” trial and emphasized that its design and durability data are directly shaping real-world decision-making.

“This is a head-to-head trial addressing an unmet need that we have in the treatment of our patients with exposure to anti-TNF therapy. This is a common clinical problem that we have,” Atreya explained. “I'm glad that I'm practicing in these times where we have a lot of therapeutic options. In the setting of previous anti TNF failure, where we already know these are hard to treat patients, because failure to anti TNF is like a surrogate marker for severe disease, hard to treat disease, refractory disease. So having these biological options is very nice, but when choosing the second advanced therapy, you have to make the right choice.”

He stressed that the head-to-head comparison of risankizumab and ustekinumab provided critically needed direct comparative data in this hard-to-treat population, something that has historically been lacking in Crohn’s disease.

The analysis included 224 patients who completed part 1 of the SEQUENCE study (week 48) and could receive risankizumab 360mg subcutaneously (SC) every 8 weeks in part 2, the open-label maintenance period of the SEQUENCE trial, starting at week 52.

Results showed patients with moderate-to-severe Crohn’s disease and prior anti-TNF failure, a population generally considered to have more refractory disease, demonstrated durable clinical remission, endoscopic response, endoscopic remission, and mucosal healing through 148 weeks of risankizumab treatment in the SEQUENCE study.

Of note, most patients who achieved clinical remission at week 8 maintained clinical remission throughout later time points, and clinical remission at week 148 was achieved by the majority (98.5% by CDAI; 88.1% by SF/APS) of week 8 clinical remitters.

Investigators additionally observed durability of clinical remission throughout later time points in patients who achieved clinical remission at week 48.

Of patients who achieved endoscopic response, endoscopic remission, or mucosal healing at week 24, 84.7%, 78.2%, and 67.3% of patients, respectively, maintained the corresponding endpoint at week 148. Similar results at week 148 were observed for patients who achieved these endoscopic endpoints at week 48.

Atreya further emphasized that early response appears to be the strongest predictor of long-term success. While molecular predictors remain elusive, he noted that patients who achieve early clinical and endoscopic remission are most likely to sustain benefit over time.

“With the amazing treatment results that we see in the SEQUENCE study and the sustained effectiveness seen in the open label extension studies, this is really something that helps us to position risankizumab high up in my personal therapeutic algorithm,” Atreya said.

Editors’ Note: Atreya reports relevant disclosures with AbbVie, Abivax, AlfaSigma, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion Healthcare, Gilead, GlaxoSmithKline, Johnson & Johnson, Lilly, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, and others.

References

1. R Atreya, J Lindsay, M Ferrante, B Siegmund, Q Cao, S Van Haaren, J Crowley, T Anschutz, A Garrison, X Huang, M C Dubinsky, DOP004 Durable Efficacy of Risankizumab Through Week 148 in Patients With Moderate-to-Severe Crohn’s Disease: A Post Hoc Analysis of Part 2 of the SEQUENCE Study, Journal of Crohn's and Colitis, Volume 20, Issue Supplement_1, January 2026, jjaf231.041, https://doi.org/10.1093/ecco-jcc/jjaf231.041

2. Brooks A. Marla Dubinsky, MD: Clinical Outcomes with Risankizumab Versus Ustekinumab in SEQUENCE. HCPLive. February 24, 2024. Accessed February 20, 2026. https://www.hcplive.com/view/marla-dubinsky-md-clinical-outcomes-risankizumab-ustekinumab-sequence