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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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13072070 - 03 Apr 2024

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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 [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13072002 - 29 Mar 2024

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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. [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13061539 - 07 Mar 2024

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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 [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13051357 - 27 Feb 2024

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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, [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm12144853 - 24 Jul 2023

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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 ≥ [...] Read more.

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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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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13051519 - 06 Mar 2024

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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 [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm13010130 - 26 Dec 2023

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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 [...] Read more.

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://0-doi-org.brum.beds.ac.uk/10.3390/jcm12196292 - 29 Sep 2023

Cited by 1 | Viewed by 1832

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 [...] Read more.

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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