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Current Challenges in Inflammatory Bowel Diseases
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Current Challenges in Inflammatory Bowel Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: 30 December 2025 | Viewed by 4233

Special Issue Editor

Dr. Wesley M. Raup-Konsavage

E-Mail Website
Guest Editor
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA
Interests: cannabis; cancer; inflammatory bowel disease; pain; cannabinoids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The multifactorial etiologies of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), contribute to the difficulties in developing effective treatments. IBD is caused by immunological dysregulation, environmental triggers, and a genetic predisposition, and is also characterized by persistent, recurrent gastrointestinal tract inflammation.

Even with the development novel medications, including immunomodulators, managing and treating IBD still presents many difficulties, particularly due to immunogenicity and variable responsiveness in patients. The variability in disease presentation and development is a significant challenge that makes early diagnosis and individualized treatment more difficult. The intrusive nature of current diagnostic methods, such as endoscopy and imaging, may make it difficult to forecast the severity of the disease or its complications, such as strictures, fistulas, or colorectal cancer. Disparities in care are made worse by the cost of these treatments.

IBD can also lead to increased risk of anxiety, depression, and a lower quality of life. Furthermore, progress toward preventative measures is hampered by a lack of clarity regarding the precise impact of environmental variables and gut bacteria. In this Special Issue, we invite authors to contribute studies around the mechanism of IBD, novel treatments, improving quality of life, and related topics.

Dr. Wesley M. Raup-Konsavage
Guest Editor

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Keywords

  • ulcerative colitis
  • Chron’s disease
  • inflammatory bowel disease
  • colitis-associated cancer
  • novel pharmaceutics

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Published Papers (4 papers)

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Research

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15 pages, 2651 KB  
Article
Orally Administered CBD/CBG Hemp Extract Reduces Severity of Ulcerative Colitis and Pain in a Murine Model
by Shivani S. Godbole, Dongxiao Sun, Matthew D. Coates, Victoria J. Himmelberger, Diana E. Roopchand and Wesley M. Raup-Konsavage
J. Clin. Med. 2025, 14(17), 6095; https://doi.org/10.3390/jcm14176095 - 28 Aug 2025
Viewed by 915
Abstract
Background: Ulcerative colitis (UC) is an autoimmune disorder characterized by inflammation of the mucosa that gives rise to a disrupted epithelial morphology. Persistent or recurrent inflammation and the debilitating nature of the associated symptoms make treatment of UC challenging. Cannabinoids derived from Cannabis [...] Read more.
Background: Ulcerative colitis (UC) is an autoimmune disorder characterized by inflammation of the mucosa that gives rise to a disrupted epithelial morphology. Persistent or recurrent inflammation and the debilitating nature of the associated symptoms make treatment of UC challenging. Cannabinoids derived from Cannabis sativa L. have been used for treatment of gastrointestinal disorders due to the wide-ranging therapeutic benefits of these compounds. Methods: We evaluated a commercial hemp extract, high in cannabigerol (CBG) and cannabidiol (CBD), as a novel treatment for UC symptoms using the dextran sodium sulfate (DSS) model in mice. Hemp extract was administered via two different routes of administration, intraperitoneal (i.p) and oral (p.o). Results: Specifically, we observed that cannabinoid treatment reduced damage to the colonic epithelium. We also observed that CBG/CBD rich hemp extracts help reduce pain-related responses in these animals. Conclusions: Together, the data suggest that cannabinoid administration has the potential to be an effective alternate therapeutic option for UC management. Full article
(This article belongs to the Special Issue Current Challenges in Inflammatory Bowel Diseases)
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17 pages, 2034 KB  
Article
Comparative Outcomes of Adalimumab and Infliximab Dose Escalation in Inflammatory Bowel Disease Patients Failing First-Line Biologic Treatment
by Ali Atay, Yavuz Cagir, Mucahit Ergul, Oguz Ozturk, Muhammed Bahaddin Durak and Ilhami Yuksel
J. Clin. Med. 2025, 14(4), 1228; https://doi.org/10.3390/jcm14041228 - 13 Feb 2025
Cited by 1 | Viewed by 1527
Abstract
Background/Objectives: Dose escalation has been commonly used to achieve and maintain response. We aimed to compare the outcomes of adalimumab or infliximab dose escalation in inflammatory bowel disease (IBD) patients. Methods: Treatment persistence (TP) and predictive factors for remission-free treatment discontinuation (r-fTD) were [...] Read more.
Background/Objectives: Dose escalation has been commonly used to achieve and maintain response. We aimed to compare the outcomes of adalimumab or infliximab dose escalation in inflammatory bowel disease (IBD) patients. Methods: Treatment persistence (TP) and predictive factors for remission-free treatment discontinuation (r-fTD) were evaluated in patients treated with adalimumab or infliximab dose escalation between 2019 and 2024. Results: Dose escalation was identified in 142 patients treated with adalimumab (UC: 23.9%; CD: 76.1%) and in 126 patients treated with infliximab (UC: 23.8%; CD: 76.2%). The TP rate was significantly lower in the adalimumab group (35.2%) than the infliximab group (53.2%) (p = 0.003). The survival analysis showed that drug persistence was lower in the adalimumab group compared with the infliximab group (mean time: 74.3 vs. 99.5 months, p < 0.001). TP rates showed no significant differences between UC and CD for both adalimumab (mean time UC: 64.7 months vs. CD: 76.2 months, p = 0.403) and infliximab (mean time UC: 80.3 months and CD: 102.6 months, p = 0.151). The r-fTD rates were significantly higher in the adalimumab group (62.7%) than the infliximab group (39.7%) (p < 0.001). Primary lack of response and secondary loss of response (sLOR) rates were both higher in the adalimumab group (7.7% and 51.4%) than the infliximab group (1.6% and 28.6%). However, serious adverse events were lower in the adalimumab group (2.1%) than the infliximab group (7.9%) (p = 0.027). Conclusions: Infliximab dose escalation was more effective than adalimumab in both UC and CD patients. Regarding the side effect profile, adalimumab dose escalation was found to be safer compared with infliximab. Full article
(This article belongs to the Special Issue Current Challenges in Inflammatory Bowel Diseases)
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Review

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21 pages, 493 KB  
Review
The Cardiovascular Effects of Inflammatory Bowel Disease Therapy with Biologics and Small Molecules: A Comprehensive Review
by Eleftheria M. Mastoridou, Fotios S. Fousekis, Xenofon M. Sakellariou, Konstantinos Mpakogiannis, Dimitrios N. Nikas, Lampros K. Michalis, Konstantinos H. Katsanos and Haralampos Milionis
J. Clin. Med. 2025, 14(18), 6476; https://doi.org/10.3390/jcm14186476 - 14 Sep 2025
Viewed by 340
Abstract
Background/Objectives: Ιnflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly associated with cardiovascular (CV) complications, such as heart failure (HF), arrhythmias, and acute coronary syndromes (ACSs). As the therapeutic landscape of IBD evolves, with the introduction of newer [...] Read more.
Background/Objectives: Ιnflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly associated with cardiovascular (CV) complications, such as heart failure (HF), arrhythmias, and acute coronary syndromes (ACSs). As the therapeutic landscape of IBD evolves, with the introduction of newer biologics and small molecules, their CV safety warrants critical evaluation. The objective of this review is to provide an update on the current evidence of CV risks associated with IBD treatments. Methods: A comprehensive literature search from inception to April 2025 was conducted using PubMed and Medline to identify randomized controlled trials, observational studies, systematic reviews, as well as pharmacovigilance data reporting CV safety outcomes of biologic and small-molecule drugs approved for IBD. Additionally, analysis of the European Summary of Product Characteristics for each agent was also performed. Results: Anti-TNF agents, particularly infliximab, have been associated with increased reporting of HF and arrhythmias, particularly in patients with pre-existing cardiac disease. Ustekinumab and vedolizumab show consistently favorable CV safety profiles across trials and real-world studies. IL-23p19 inhibitors demonstrate low CV event rates overall, although signals for atrial fibrillation have emerged with risankizumab. Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators carry class-specific CV warnings, due to signals mainly on non-IBD populations, and require careful use in high-risk individuals. Conclusions: Although most IBD therapies are generally safe from a CV perspective, certain agents may pose risks in vulnerable patients. Individualized CV risk assessment and ongoing post-marketing surveillance are essential to guide therapeutic choices and ensure patient safety. Full article
(This article belongs to the Special Issue Current Challenges in Inflammatory Bowel Diseases)
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Other

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17 pages, 1520 KB  
Systematic Review
Efficacy of Biologic Agents and Small Molecules for Endoscopic Improvement and Mucosal Healing in Patients with Moderate-to-Severe Ulcerative Colitis: Systematic Review and Meta-Analysis
by Christos Mademlis, Anastasia Katsoula, Theocharis Koufakis, Paschalis Paschos, Aristeidis Kefas, Lefteris Teperikidis, Niki Theodoridou and Olga Giouleme
J. Clin. Med. 2025, 14(16), 5789; https://doi.org/10.3390/jcm14165789 - 15 Aug 2025
Viewed by 959
Abstract
Background and Aim: The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints [...] Read more.
Background and Aim: The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints in moderate to severe UC. Methods: A systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science and grey literature was conducted through November 2024. Separate meta-analyses were performed for induction and maintenance. A random-effects model was used to estimate relative risks (RR), with 95% confidence intervals (CI), and confidence in estimates was evaluated with the GRADE approach (Grading of Recommendation Assessment, Development and Evaluation). Results: We included 40 RCTs (13 therapies, 14,369 patients). Thirty-two trials provided data in induction and twenty-eight in maintenance. During induction, all biologic therapies, except mirikizumab and filgotinib 100 mg, demonstrated superiority over placebo (RR 2.02, 95% CI: 1.76–2.31, I2 = 72%) for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 5.53, 95% CI: 3.78–8.09). For mucosal healing, all interventions were superior to placebo (RR 2.95, 95% CI: 2.11–4.13, I2 = 61%), except filgotinib 100 mg. Risankizumab showed the highest efficacy (RR 10.25, 95% CI: 2.49–42.11). In maintenance, all therapies showed superiority over placebo for endoscopic improvement. For mucosal healing all therapies were superior to placebo, except risankizumab. Upadacitinib 30 mg showed the highest efficacy (RR 4.01, 95% CI: 1.81–8.87). Conclusions: Biologic and small-molecule therapies demonstrated substantial efficacy in achieving key endpoints. Standardized outcome definitions and further head-to-head RCTs are essential to strengthen confidence in our findings. Full article
(This article belongs to the Special Issue Current Challenges in Inflammatory Bowel Diseases)
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