Editorial: Risankizumab in Refractory Crohn's Disease—From Real‐World Effectiveness to Strategic Positioning and Early Monitoring. Authors' Reply

Dear Editor,

We sincerely thank Ernest‐Suárez and Hoentjen for their thoughtful editorial and insightful appraisal of the RISANCROHN study [1], and appreciate their perspective on the role of real‐world evidence in refining the positioning of selective IL‐23 inhibition in Crohn's disease (CD).

Beyond representing the largest real‐world cohort reported to date [2], we believe RISANCROHN's greatest strength lies in the complexity of the included population. The nationwide ENEIDA registry reflects routine clinical practice across diverse centres, enhancing external validity [3]. Almost 90% of patients had been exposed to anti‐TNF agents, 69% to ustekinumab, half had undergone intestinal surgery, and nearly half had failed at least three advanced therapies. Almost 90% had ileal or ileocolonic disease, with a high prevalence of stricturing, penetrating, and perianal phenotypes—a population often underrepresented in registrational trials but, in our opinion, more representative of the difficult‐to‐treat patients seen in daily practice. Despite these unfavourable baseline characteristics, more than half of patients achieved steroid‐free clinical remission after induction, with sustained effectiveness at follow‐up [2].

These findings complement the pivotal ADVANCE, MOTIVATE and FORTIFY trials, demonstrating that risankizumab's effectiveness extends to a substantially more treatment‐experienced population encountered in routine practice [4, 5]. Our results are also consistent with recent real‐world cohorts, including the Canadian multicentre experience after ustekinumab failure [6] and the Italian RESOLVE study [7], supporting reproducibility across healthcare settings despite variations in patient characteristics and outcome definitions.

Faecal calprotectin may underestimate inflammatory activity in isolated small bowel CD [8], making objective assessment challenging. Nevertheless, the concordant improvement in clinical outcomes, biomarkers, and available endoscopic data supports the overall consistency of our findings. We fully agree with the Editorial's comment on the use of ultrasound in ileal CD; in Spain, we have developed recommendations to increase its use in clinical practice [9].

One of RISANCROHN's most clinically relevant findings concerns treatment sequencing. While previous ustekinumab exposure influenced outcomes in unadjusted analyses, cumulative advanced therapy exposure emerged as the main independent determinant of remission [2]. Similar observations have been reported elsewhere, where prior ustekinumab exposure reflected a more refractory disease course rather than true mechanistic failure of subsequent IL‐23 inhibition [2]. Together, these findings suggest that cumulative treatment burden better reflects refractoriness than failure of a specific mechanism of action, supporting earlier positioning of IL‐23 inhibition to maximise clinical benefit [2, 4, 5, 6, 7].

Finally, it is worth noting that risankizumab was the first IL‐23 inhibitor approved for CD in our country, although mirikizumab and guselkumab have since also been approved. We expect RWE data on these agents from the ENEIDA registry in the coming months, allowing direct comparison with RISANCROHN in a similarly refractory population [2, 3].

Author Contributions

Rocio Ferreiro‐Iglesias: conceptualization, writing – original draft. Manuel Barreiro‐de Acosta: conceptualization, validation, writing – review and editing, supervision, data curation. Yamile Zabana: writing – review and editing, supervision.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].

Linked Articles

This article is linked to Barreiro‐de Acosta et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70858 and https://doi.org/10.1111/apt.70783.

Ferreiro‐Iglesias R., Zabana Y., and Barreiro‐de Acosta M., “Editorial: Risankizumab in Refractory Crohn's Disease—From Real‐World Effectiveness to Strategic Positioning and Early Monitoring. Authors' Reply,” Alimentary Pharmacology & Therapeutics 64, no. 6 (2026): 839–840, 10.1111/apt.70898.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.