A therapeutic atlas of monogenic inflammatory bowel disease
Year: 2026
Type: review
Study design: Systematic Review
Abstract: BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n = 62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.
Source: Journal of Crohn s and Colitis
Authors: Pai-Jui Yeh, James E G Charlesworth, Henry Taylor, James J Ashton, Katrina Nash, Kin Hang Lam, Lissy de Ridder, Stephanie A Vuijk, Ziqing Ye, Ying Huang, Tania Bildstein, Wolfram Haller, Kelsey D J Jones, Dror S Shouval, Batia Weiss, Yu Lung Lau, Quynh Bui-Thi-Thuy, Aleixo M Muise, Duncan Richards, Simon Travis, Dan Turner, Holm H Uhlig
Institutions: Centre for Human Genetics, Chang Gung Memorial Hospital, University of Oxford, Linkou Chang Gung Memorial Hospital, Kennedy Institute of Rheumatology, Southampton Children's Hospital, University of Southampton, Oxford University Hospitals NHS Trust, Leiden University Medical Center, Willem-Alexander Kinderziekenhuis, Erasmus MC - Sophia Children’s Hospital, Fudan University, Children's Hospital of Fudan University, Great Ormond Street Hospital, Birmingham Children's Hospital, University of Birmingham, Tel Aviv University, Schneider Children's Medical Center, Sheba Medical Center, University of Hong Kong, Vietnam National Children's Hospital, University of Toronto, Hospital for Sick Children, University of Cambridge, Hebrew University of Jerusalem, Shaare Zedek Medical Center, Bikur Cholim Hospital
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
OpenAlex ID: W7212383362