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Targeted Treatment in Inflammatory Bowel Diseases (IBD)

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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: closed (30 August 2024) | Viewed by 17761

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Special Issue Editors

Dr. Brigida Barberio

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Guest Editor

Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy
Interests: inflammatory bowel disease; short bowel syndrome; microbiota; irritable bowel syndrome

Dr. Catalán-Serra Ignacio

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Guest Editor

1. Levanger Hospital, Nord Trondelag Hopsital Trust, 7600 Levanger, Norway
2. IBD Research Group, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
3. Centre for Molecular Inflammation Research, 7034 Trondheim, Norway
Interests: inflammatory bowel disease; gastroenterology, mucosal immunology; T cells; microbiome; precision medicine in IBD

Dr. Davide Giuseppe Ribaldone

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Guest Editor

Department of Medical Sciences, University of Turin, 10124 Turin, Italy
Interests: inflammatory bowel diseases; Crohn’s disease; ulcerative colitis; celiac disease; microbiota; eosinophilic esophagitis; irritable bowel syndrome; biologics; diverticular disease; Helicobacter pylori
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Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBD) constitute a complex group of diseases that require targeted treatment approaches to improve patient outcomes and minimize side effects. This Special Issue welcomes original research articles, reviews, and perspectives that focus on the development, optimization, and clinical translation of targeted treatments for IBD. We encourage submissions that cover topics including but not limited to the molecular mechanisms of IBD pathogenesis, the identification and validation of potential targets, the design and testing of novel drugs or biologics, the evaluation of biomarkers or imaging techniques for personalized therapy, and the outcomes and challenges of clinical trials. However, mini-reviews and case reports will not be considered. This Special Issue is expected to contribute to advancing the knowledge and practice of targeted treatment in IBD and promoting dialogue among researchers, clinicians, and patients.

Dr. Brigida Barberio
Dr. Catalán-Serra Ignacio
Dr. Davide Giuseppe Ribaldone
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Inflammatory Bowel Disease (IBD)
targeted treatment
crohn's disease
ulcerative colitis
biologic therapy

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Published Papers (10 papers)

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Research

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25 pages, 5726 KiB

Open AccessArticle

The Combined Administration of Eicosapentaenoic Acid (EPA) and Gamma-Linolenic Acid (GLA) in Experimentally Induced Colitis: An Experimental Study in Rats

by Orestis Ioannidis, Angeliki Cheva, Ioannis Varnalidis, Ioannis Koutelidakis, Vasileios Papaziogas, Panagiotis Christidis, Elissavet Anestiadou, Konstantinos Aggelopoulos, Ioannis Mantzoros, Manousos George Pramateftakis, Efstathios Kotidis, Barbara Driagka, Stamatios Aggelopoulos and Evangelos J. Giamarellos-Bourboulis

J. Clin. Med. 2024, 13(22), 6661; https://doi.org/10.3390/jcm13226661 - 6 Nov 2024

Viewed by 414

Abstract

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited effective treatments, prompting the need for investigation of novel therapeutic approaches. Eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) have demonstrated potential anti-inflammatory properties, but their combined effects on UC have not been thoroughly investigated. This study aimed to evaluate the effect of the combined administration of EPA and GLA on clinical and histopathologic features of experimental UC models. Methods: Thirty-six male Wistar rats were randomized in three groups (DSS group, Ensure Plus group, and Oxepa group), with twelve rats in each group. Experimental colitis was induced by administrating dextran sulfate sodium (DSS) 8%. The DSS group received tap water, the Ensure Plus group was given a high caloric diet, and the Oxepa group received a special diet containing high levels of EPA and GLA. Disease activity index (DAI) and microscopic activity index (MAI) were measured. Inflammatory markers were calculated both in blood and large intestine, liver, spleen, and lung tissue samples. Neutrophil and macrophage populations were assessed with immunohistochemistry. Results: No significant differences in the DAI index were found between the groups, but the MAI revealed statistically significant differences (p < 0.001). While no significant differences were observed in tumor necrosis factor-alpha (TNF-α) levels, interleukin-17 (IL-17) levels in the large intestine showed statistically significant differences (p = 0.05), with the Ensure Plus and Oxepa groups displaying lower levels compared to the DSS group (p = 0.021 and p = 0.043, respectively). Significant differences in neutrophil infiltration were found in both the large intestine (p < 0.001) and lungs (p = 0.002), with the Oxepa group showing fewer cells. Similarly, significant differences in macrophage infiltration were observed in the large intestine (p = 0.038) and spleen (p < 0.001), with the Oxepa group having lower macrophage counts. Conclusions: In conclusion, the combination of EPA and GLA demonstrates local anti-inflammatory effects and improves the histopathological outcomes in UC. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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15 pages, 864 KiB

Open AccessArticle

The Impact of Phenotype of Inflammatory Bowel Diseases, Inflammation Activity and Therapy on Mucosal Mature Cd83⁺ Dendritic Cell

by Bruna Rošić Despalatović, Marija Babić, Andre Bratanić, Ante Tonkić, Žarko Ardalić and Katarina Vilović

J. Clin. Med. 2024, 13(7), 2070; https://doi.org/10.3390/jcm13072070 - 3 Apr 2024

Viewed by 942

Abstract

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are well-defined phenotypes of chronic inflammatory bowel diseases (IBDs). A mechanism of inflammation in these diseases is partially controlled by the intestinal dendritic cell (DC). In this study, we observed a mature CD83⁺ DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: The study included 219 subjects: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with the primary antibody Anti-CD83. Intraepithelial CD83⁺ DCs were counted per 100 enterocytes. The presence of CD83⁺ DC was analysed according to the type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83⁺ DCs (0, ≥1) differed according to disease types of IBD (p = 0.001), histologic inflammation activity (p = 0.049) and applied therapy (p = 0.001). The odds for CD83⁺ DC presence were 5.2 times higher in the CD group than in the control/UC group. The odds for CD83⁺ DC presence were 2.6 times higher in subjects without inflammation or chronic inflammation than with acute inflammation. They were also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83⁺ DC (Rock analysis area = 0.699; SE 0.046; p < 0.001; 95% CI: 0.609–0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83⁺ DC could be used as a possible parameter in distinction between UC and CD, as well as a predictor of inflammation activity and treatment outcome. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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10 pages, 752 KiB

Open AccessArticle

Burden of Mental Health among Patients with Inflammatory Bowel Disease—A Cross-Sectional Study from a Tertiary IBD Center in Hungary

by Livia Lontai, Lívia Priyanka Elek, Fruzsina Balogh, Dorottya Angyal, Péter Pajkossy, Lorant Gonczi, Peter L. Lakatos and Ákos Iliás

J. Clin. Med. 2024, 13(7), 2002; https://doi.org/10.3390/jcm13072002 - 29 Mar 2024

Cited by 1 | Viewed by 1263

Abstract

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient’s quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn’s disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate–severe anxiety disorder, and 22% were affected by moderate–severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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16 pages, 1608 KiB

Open AccessArticle

Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M Levels and Clinical and Biochemical Outcomes in Patients with Crohn’s Disease

by Luisa Bertin, Brigida Barberio, Alessandro Gubbiotti, Lorenzo Bertani, Francesco Costa, Linda Ceccarelli, Pierfrancesco Visaggi, Giorgia Bodini, Andrea Pasta, Renato Sablich, Maria Teresa Urbano, Antonio Ferronato, Andrea Buda, Manuela De Bona, Giulio Del Corso, Alessandro Massano, Imerio Angriman, Marco Scarpa, Fabiana Zingone and Edoardo Vincenzo Savarino

J. Clin. Med. 2024, 13(6), 1539; https://doi.org/10.3390/jcm13061539 - 7 Mar 2024

Viewed by 1493

Abstract

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn’s disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point (p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy (p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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11 pages, 1540 KiB

Open AccessArticle

Switching from Intravenous to Subcutaneous Biological Therapy for Inflammatory Bowel Disease Patients Remains a Challenge

by Vered Richter, Daniel L. Cohen, Ofra Kriger-Sharabi, Dana Zelnik Yovel, Nadav Kochen, Efrat Broide and Haim Shirin

J. Clin. Med. 2024, 13(5), 1357; https://doi.org/10.3390/jcm13051357 - 27 Feb 2024

Viewed by 1379

Abstract

Biological inflammatory bowel disease (IBD) medications, once limited to intravenous (IV) administration, can now be administered both via IV and subcutaneously (SC). This study investigates patient preferences, willingness to switch from IV to SC, and associated factors. A questionnaire covering demographics, disease-related inquiries, quality of life, and IBD medication preferences was distributed via email, the Israeli Crohn’s Disease and Ulcerative Colitis Foundation, infusion centers, and clinics. From 454 IBD patients (median age: 42 years; 55.7% female), responses revealed a preference for SC every 8 weeks, which is comparable to daily oral dosing. Both options were significantly favored over IV every 8 weeks and SC every 2 weeks, with no statistically significant differences between the latter two. However, among patients who were experienced with both SC and IV administration, a clear preference for SC administration every 2 weeks over IV every 8 weeks surfaced. Among IV-treated patients, 54.5% resisted switching to SC. Key reasons for this included medical staff presence (57.7%), a fear of needles (46.4%), belief in infusion efficacy (37.1%), and longer intervals between infusions (36.1%). Findings suggest that transitioning from IV to SC treatment is challenging due to patient resistance, which is influenced by specific factors. Identifying and addressing these obstacles is crucial for optimizing IBD management. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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12 pages, 1608 KiB

Open AccessArticle

Factors Associated with Response to Systemic Corticosteroids in Active Ulcerative Colitis: Results from a Prospective, Multicenter Trial

by Andreas Blesl, Andrea Borenich, Hans Peter Gröchenig, Gottfried Novacek, Christian Primas, Walter Reinisch, Maximilian Kutschera, Constanze Illiasch, Barbara Hennlich, Pius Steiner, Robert Koch, Wolfgang Tillinger, Thomas Haas, Gerhard Reicht, Andreas Mayer, Othmar Ludwiczek, Wolfgang Miehsler, Karin Steidl, Lukas Binder, Franziska Baumann-Durchschein, Stefan Fürst, Simon Reider, Christina Watschinger, Heimo Wenzl, Alexander Moschen, Andrea Berghold and Christoph Högenauer Show full author list Hide full author list

J. Clin. Med. 2023, 12(14), 4853; https://doi.org/10.3390/jcm12144853 - 24 Jul 2023

Viewed by 1935

Abstract

Background: Among patients with ulcerative colitis, 30–50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. Methods: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. Results: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. Conclusion: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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Review

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19 pages, 1462 KiB

Open AccessReview

Safety and Effectiveness of Thiopurines and Small Molecules in Elderly Patients with Inflammatory Bowel Diseases

by Aleksandra Strigáč, Miłosz Caban, Ewa Małecka-Wojciesko and Renata Talar-Wojnarowska

J. Clin. Med. 2024, 13(16), 4678; https://doi.org/10.3390/jcm13164678 - 9 Aug 2024

Viewed by 1082

Abstract

The management of inflammatory bowel diseases (IBD) requires weighing an individual patient’s therapeutic benefits and therapy-related complication risks. The immunomodulators that have been commonly used so far in IBD therapy are thiopurines, including 6-mercaptopurine and azathioprine. As our understanding of the IBD pathomechanisms is widening, new therapeutic approaches are being introduced, including the Janus kinase (JAK) inhibitors and Sphingosine 1-phosphate receptor (S1PR) modulators’ development. Non-selective JAK inhibitors are represented by tofacitinib, while selective JAK inhibitors comprise filgotinib and upadacitinib. As for the S1PR modulators, ozanimod and etrasimod are approved for UC therapy. The number of elderly patients with IBD is growing; therefore, this review aimed to evaluate the effectiveness and safety of the oral immunomodulators among the subjects aged ≥60. Possible complications limit the use of thiopurines in senior patients. Likewise, the promising effectiveness of new drugs in IBD therapy in those with additional risk factors might be confined by the risk of serious adverse events. However, the data regarding this issue are limited. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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16 pages, 3841 KiB

Open AccessReview

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms

by Giammarco Mocci, Antonio Tursi, Francesca Maria Onidi, Paolo Usai-Satta, Giovanni Mario Pes and Maria Pina Dore

J. Clin. Med. 2024, 13(5), 1519; https://doi.org/10.3390/jcm13051519 - 6 Mar 2024

Cited by 1 | Viewed by 2609

Abstract

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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15 pages, 663 KiB

Open AccessFeature PaperReview

Cytomegalovirus Infection: An Underrated Target in Inflammatory Bowel Disease Treatment

by Rossella Maresca, Simone Varca, Federica Di Vincenzo, Maria Elena Ainora, Irene Mignini, Alfredo Papa, Franco Scaldaferri, Antonio Gasbarrini, Maria Cristina Giustiniani, Maria Assunta Zocco and Lucrezia Laterza

J. Clin. Med. 2024, 13(1), 130; https://doi.org/10.3390/jcm13010130 - 26 Dec 2023

Cited by 1 | Viewed by 2404

Abstract

CMV infection is still a matter of concern in IBD patients, especially regarding the disease’s relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. Various techniques, ranging from serology to histology, can be employed to detect intestinal CMV infection; however, there is currently disagreement in the literature regarding the most effective diagnostic test. Furthermore, CMV involvement in steroid resistance has been broadly discussed, but whether CMV infection is a cause or consequence of the disease severity and, consequently, steroid refractoriness is still debated. Its potential contribution to the lack of response to advanced therapy and small molecules must be more valued and wholly explored. In this review, we look at the actual literature on CMV in IBD patients, and we suggest a pragmatic algorithm for clinical practice management of CMV infection. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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18 pages, 754 KiB

Open AccessReview

Benefits and Challenges of Treat-to-Target in Inflammatory Bowel Disease

by Jack West, Katrina Tan, Jalpa Devi, Finlay Macrae, Britt Christensen and Jonathan P. Segal

J. Clin. Med. 2023, 12(19), 6292; https://doi.org/10.3390/jcm12196292 - 29 Sep 2023

Cited by 5 | Viewed by 3413

Abstract

There is notable disparity between symptomatology and disease activity in a significant proportion of patients with inflammatory bowel disease (IBD), and escalation of treatment based on symptoms alone can fail to significantly alter the course of disease. The STRIDE-II position statement, published in 2021 by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organisation for the Study of IBD (IOIBD) provides the most current recommendations for a treat-to-target (T2T) approach in IBD. Despite the benefits offered by a T2T approach in IBD, there are numerous drawbacks and current limitations to its widespread implementation in real-world clinical practice. Owing to the lack of a standardised definition of MH, outcome data are heterogeneous and limit the comparability of existing data. Further, studies investigating the likelihood of achieving MH with a T2T approach are limited and largely retrospective. Evidence of the real-world feasibility of tight monitoring is currently minimal and demonstrates sub-optimal adherence among patients. Further, the few studies on the acceptability and uptake of a T2T approach in real-world practice demonstrate the need for increased acceptability on both patients’ and clinicians’ behalf. Real-world applicability is further limited by the need for repeated endoscopic assessments of MH as well as a lack of guidance on how to incorporate the various treatment targets into therapeutic decision-making. We aim to review the benefits and challenges of the T2T approach and to discuss potential solutions to further patient care. Full article

(This article belongs to the Special Issue Targeted Treatment in Inflammatory Bowel Diseases (IBD))

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