Soldera J, Pertile MAS, Carobin LN, Brambilla DJF, Brambilla E. Beyond class switching in multi-refractory inflammatory bowel disease: Nine case reports and review of literature. World J Gastrointest Pharmacol Ther 2026; 17(3): 120771 [DOI: 10.4292/wjgpt.120771]
Corresponding Author of This Article
Jonathan Soldera, MD, MSc, PhD, Tutor, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Llantwit Road, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
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Gastroenterology & Hepatology
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case-report
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World Journal of Gastrointestinal Pharmacology and Therapeutics
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2150-5349
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Soldera J, Pertile MAS, Carobin LN, Brambilla DJF, Brambilla E. Beyond class switching in multi-refractory inflammatory bowel disease: Nine case reports and review of literature. World J Gastrointest Pharmacol Ther 2026; 17(3): 120771 [DOI: 10.4292/wjgpt.120771]
World J Gastrointest Pharmacol Ther. Sep 5, 2026; 17(3): 120771 Published online Sep 5, 2026. doi: 10.4292/wjgpt.120771
Beyond class switching in multi-refractory inflammatory bowel disease: Nine case reports and review of literature
Jonathan Soldera, Maria Antonia Selbach Pertile, Leticia Nodari Carobin, Daniel Jun Funatsu Brambilla, Eduardo Brambilla
Jonathan Soldera, Tutor, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Cardiff CF37 1DL, United Kingdom
Jonathan Soldera, Department of Gastroenterology, Logan Hospital, Brisbane 4131, Queensland, Australia
Maria Antonia Selbach Pertile, Leticia Nodari Carobin, Daniel Jun Funatsu Brambilla, School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95070-560, Rio Grande do Sul, Brazil
Eduardo Brambilla, Department of Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, RS, Brazil
Co-first authors: Jonathan Soldera and Maria Antonia Selbach Pertile.
Author contributions: Soldera J, Pertile MAS, Carobin LN, Brambilla DJF, and Brambilla E contributed to data collection and writing of the first draft of the manuscript; Soldera J and Pertile MAS contributed equally to this manuscript as co-first authors; Soldera J and Brambilla E critically revised the manuscript. All authors have read and approved the final version of the manuscript.
AI contribution statement: Portions of this manuscript were edited using ChatGPT solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Jonathan Soldera, MD, MSc, PhD, Tutor, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Llantwit Road, Pontypridd, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Received: March 9, 2026 Revised: May 15, 2026 Accepted: June 10, 2026 Published online: September 5, 2026 Processing time: 173 Days and 20.8 Hours
Abstract
BACKGROUND
A clinically relevant subset of patients with inflammatory bowel disease (IBD) remain partial responders despite multiple advanced therapies. In this setting, reflexive class switching risks forfeiting incremental mechanistic gains, whereas a deliberate “build-on-partial-response” strategy - through dose optimization, extended induction, and, in selected cases, advanced combination therapy (ACT) [an oral Janus kinase inhibitor (iJAK) plus a biologic] - may consolidate disease control. However, real-world data supporting ACT remain limited, particularly regarding phenotype-driven selection, objective reassessment, and safety considerations.
CASE SUMMARY
We report nine multi-refractory IBD patients [ulcerative colitis (UC), n = 5; Crohn’s disease, n = 4] managed with ACT after incomplete response to an initial advanced therapy. UC strategies included infliximab plus tofacitinib, ustekinumab plus tofacitinib, and vedolizumab combined with iJAK. Crohn’s disease cases illustrate three patterns: Add-on anti-tumor necrosis factor therapy after partial iJAK response (e.g., upadacitinib plus adalimumab in two patients with stenosing or perianal phenotypes), interleukin-23 pathway intensification combined with iJAK (guselkumab plus tofacitinib), and phenotype discordance between extraintestinal and luminal disease control. Overall, 8/9 patients (89%) achieved clinical response with improvement in biochemical markers and/or endoscopic findings; among these, 6/9 (67%) achieved documented deep remission (clinical and biochemical, with endoscopic confirmation in 5/6). One patient with severe refractory UC failed ustekinumab plus tofacitinib and infliximab rescue and proceeded to colectomy with ileal pouch construction (11%). Patients did not present any adverse event associated with therapy, only secondary to uncontrolled disease.
CONCLUSION
In multi-refractory IBD, add-on ACT may convert partial response into deep remission, averting surgery in selected patients.
Core Tip: Multi-refractory inflammatory bowel disease often stalls at a “near-working” partial response to an advanced therapy. This case series (n = 9) suggests that, in carefully selected patients, consolidating partial mechanistic control with structured optimization and add-on advanced combination therapy (an oral Janus kinase inhibitor plus a biologic) may convert incomplete response into deep remission and delay surgery. This approach requires phenotype-driven selection, objective reassessment anchored to endoscopic and biochemical endpoints, rigorous infection exclusion, close monitoring, and predefined stopping rules - recognizing that timely colectomy remains appropriate when objective control fails.
