Dear Editors,
We thank Jiang et al. for their interest in our recent study on recurrent acute pancreatitis (RAP) [1, 2]. Our report was based on large‐scale, register‐derived data and therefore detailed characterisation of episode severity and complication profiles could not be incorporated with sufficient granularity. Nonetheless, their suggestion to integrate acute pancreatitis severity into enrichment strategies for RAP trials is thoughtful and may hold value for clinical observational studies and randomised controlled trials. Operationalizing severity across recurrent events, however, presents several challenges.
Recurrent attacks are often less severe than the index episode and patients frequently experience a heterogeneous sequence of mild, moderate and severe events. This variability complicates the use of severity as a straightforward stratification variable. For instance, a patient with a severe first episode followed by two mild recurrences and then a moderate one illustrates the difficulty of consistently weighting or summarizing severity across multiple events. Length of hospital stay has been used as a surrogate marker, but it carries notable limitations and is subject to substantial inter‐institutional variation.
In addition to trial enrichment strategies based on prior pancreatitis history (event number and severity), future RAP trials could consider composite primary endpoints that integrate recurrence burden and severity with patient‐reported outcomes. A win‐ratio framework, which is increasingly applied in cardiology and recently used in a phase 2 acute pancreatitis trial, may offer a practical hierarchical structure combining, for example, time to recurrence, length of hospital stay (or other standardised measure of severity), and patient‐reported outcomes [3, 4, 5]. Such an approach prioritises clinically meaningful improvements over simple reductions in event counts and may enhance statistical efficiency, reduce required sample size and improve the feasibility of future RAP studies.
Author Contributions
Asbjørn M. Drewes: writing – review and editing. Søren S. Olesen: writing – original draft.
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 [1].
Linked Articles
This article is linked to Olesen et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70843 and https://doi.org/10.1111/apt.70820.
Acknowledgements
Declaration of Generative AI and AI Assisted Technologies: During preparation of this manuscript, Microsoft Copilot (July 2026 version) was used for language editing and drafting support. The authors reviewed and edited all AI‐assisted content and take full responsibility for the final manuscript.
Olesen S. S. and Drewes A. M., “Letter: Severity‐Informed Enrichment for Recurrent Acute Pancreatitis Trials. Authors' Reply,” Alimentary Pharmacology & Therapeutics 64, no. 7 (2026): 1019–1020, 10.1111/apt.70854.
Handling Editor: Colin Howden
Data Availability Statement
The authors have nothing to report.
References
- 1. Jiang F. and Shen T., “Letter: Severity‐Informed Enrichment for Recurrent Acute Pancreatitis Trials,” Alimentary Pharmacology & Therapeutics 64, no. 7 (2026): 1017–1018, 10.1111/apt.70843. [DOI] [PubMed] [Google Scholar]
- 2. Olesen S. S., Bruun N. H., Davidsen L., et al., “Natural History of Recurrent Acute Pancreatitis: Implications for Interventional Trial Design,” Alimentary Pharmacology & Therapeutics 64, no. 7 (2026): 976–984, 10.1111/apt.70820. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Gregson J., Taylor D., Owen R., Collier T. J., Cohen D., and Pocock S., “Hierarchical Composite Outcomes and Win Ratio Methods in Cardiovascular Trials: A Review and Consequent Guidance,” Circulation 151, no. 22 (2025): 1606–1619, 10.1161/CIRCULATIONAHA.124.070251. [DOI] [PubMed] [Google Scholar]
- 4. Cunningham J. M., Fuest S., and Burke H., “Win Ratio Method for Hierarchical Composite Outcomes in Randomized Clinical Trials,” Journal of the American Medical Association 335, no. 8 (2026): 715–716, 10.1001/jama.2025.25686. [DOI] [PubMed] [Google Scholar]
- 5. Sutton R., Garg P. K., Miller J., et al., “Zegocractin for Acute Pancreatitis With Systemic Inflammatory Response Syndrome: A Randomized, Controlled, Dose‐Ranging, Phase 2b Trial,” EClinicalMedicine 93 (2026): 103757, 10.1016/j.eclinm.2026.103757. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
The authors have nothing to report.