Combination therapy With Biologics or Small-Molecules for Inflammatory Bowel Disease: A Case Series and Meta-analysis

Combination therapy With Biologics or Small-Molecules for Inflammatory Bowel Disease: A Case Series and Meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 December 2025 V1 Latest version Share on Combination therapy With Biologics or Small-Molecules for Inflammatory Bowel Disease: A Case Series and Meta-analysis Authors : Zihan Chen 0009-0001-8775-3026 , Mengqi Chen , Jieqing Huang , LinXin Liu , Caiguang Liu , Zhirong Zeng , and Xiaojun Zhuang [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176606121.17325189/v1 124 views 75 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Biologics and small-molecules have transformed the management of inflammatory bowel disease (IBD), particularly difficult-to-treat IBD (DDT-IBD). However, the optimal combination therapy regimens for maximizing efficacy remains unclear, and data on their comparative effectiveness in different age groups are limited. Methods: We analyzed a case series of 16 patients with Crohn’s disease (CD) who underwent combination therapy by collecting demographic, clinical, laboratory, and endoscopic data. Additionally, a meta-analysis including data from our institution was conducted to estimate pooled clinical response and remission rates using a random-effects model. Results: In our case series, 43.8% of patients achieved a clinical response after 6 months of combination therapy, and 28.6% achieved clinical remission at 12 months. The meta-analysis included 14 studies with 355 patients with DDT-IBD. Pooled clinical response rates were 54% in pediatric patients and 42% in adults, and pooled clinical remission was achieved in 62% and 48% of the pediatric and adult patients, respectively, with combination therapy for a median duration of 4–9 months. Subgroup analysis revealed that anti-tumor necrosis factors (TNFs) combined with ustekinumab had higher odds of achieving clinical remission than anti-TNFs combined with vedolizumab (odds ratio, 28%; 95% confidence interval: 11–72%), particularly in pediatric patients. No other combination regimens showed superior efficacy. Conclusions: Combination therapy with biologics or small-molecules demonstrated moderate efficacy in patients with DDT-IBD who have lost response to two or more biologic monotherapies. Anti-TNFs combined with ustekinumab may be a preferred option, particularly for pediatric patients with limited therapeutic options. Supplementary Material File (manuscript.doc) Download 214.87 KB File (table 1.doc) Download 45.00 KB File (table 2.doc) Download 28.00 KB File (table 3.doc) Download 59.50 KB Information & Authors Information Version history V1 Version 1 18 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Zihan Chen 0009-0001-8775-3026 Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author Mengqi Chen Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author Jieqing Huang Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author LinXin Liu Boji Pharmaceutical Research Center View all articles by this author Caiguang Liu Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author Zhirong Zeng Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author Xiaojun Zhuang [email protected] Sun Yat-sen University First Affiliated Hospital Department of Gastroenterology View all articles by this author Metrics & Citations Metrics Article Usage 124 views 75 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zihan Chen, Mengqi Chen, Jieqing Huang, et al. Combination therapy With Biologics or Small-Molecules for Inflammatory Bowel Disease: A Case Series and Meta-analysis. Authorea . 18 December 2025. DOI: https://doi.org/10.22541/au.176606121.17325189/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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