Treatment and Management of Chronic Inflammatory Bowel Diseases: Optimizing Present and Future Therapeutic Choices

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 (15 June 2022) | Viewed by 38132

Special Issue Editor

Department of General Surgery and Gastroenterology, Tuscany North West ASL, Pontedera, Italy
Interests: inflammatory bowel diseases; biomarkers; clinical gastroenterology; translational medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The management of inflammatory bowel diseases (IBD) has been revolutionised in recent years, due to the approval of several new therapeutic options, involving new pathways of inflammation.

However, less is known about the management of the choice of the right drug to the right patient. The main goal of the future researches in IBD would be directed in this direction, identifying new drug-specific biomarkers, similar to the oncological management.

This Issue of Journal of Clinical Medicine is designed to give visibility to all studies that are able to increase knowledge in this perspective.

Dr. Lorenzo Bertani
Guest Editor

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Keywords

  • IBD
  • Biologics
  • JAK inhibitors
  • Biomarkers
  • Mucosal healing

Published Papers (14 papers)

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Editorial

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4 pages, 196 KiB  
Editorial
Treatment and Management of Chronic Inflammatory Bowel Diseases: Optimizing Present and Future Therapeutic Choices
by Lorenzo Bertani
J. Clin. Med. 2022, 11(18), 5267; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11185267 - 06 Sep 2022
Cited by 2 | Viewed by 1247
Abstract
Inflammatory bowel diseases (IBD) are chronic relapsing diseases of the gastrointestinal tract of unknown origin, resulting from an aberrant immune response to microbial and gut-specific antigens in genetically susceptible patients [...] Full article

Research

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8 pages, 1541 KiB  
Article
Machine Learning Can Predict the Probability of Biologic Therapy in Patients with Inflammatory Bowel Disease
by David Schöler, Karel Kostev, Maximilian Peters, Cosmin Zamfir, Agnieszka Wolk, Christoph Roderburg and Sven H. Loosen
J. Clin. Med. 2022, 11(15), 4586; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11154586 - 05 Aug 2022
Cited by 2 | Viewed by 1455
Abstract
Background: Inflammatory bowel disease (IBD) is of high medical and socioeconomic relevance. Moderate and severe disease courses often require treatment with biologics. The aim of this study was to evaluate machine learning (ML)-based methods for the prediction of biologic therapy in IBD patients [...] Read more.
Background: Inflammatory bowel disease (IBD) is of high medical and socioeconomic relevance. Moderate and severe disease courses often require treatment with biologics. The aim of this study was to evaluate machine learning (ML)-based methods for the prediction of biologic therapy in IBD patients using a large prescription database. Methods: The present retrospective cohort study utilized a longitudinal prescription database (LRx). Patients with at least one prescription for an intestinal anti-inflammatory agent from a gastroenterologist between January 2015 and July 2021 were included. Patients who had received an initial biologic therapy prescription (infliximab, adalimumab, golimumab, vedolizumab, or ustekinumab) were categorized as the “biologic group”. The potential predictors included in the machine learning-based models were age, sex, and the 100 most frequently prescribed drugs within 12 months prior to the index date. Six machine learning-based methods were used for the prediction of biologic therapy. Results: A total of 122,089 patients were included in this study. Of these, 15,824 (13.0%) received at least one prescription for a biologic drug. The Light Gradient Boosting Machine had the best performance (accuracy = 74%) and was able to correctly identify 78.5% of the biologics patients and 72.6% of the non-biologics patients in the testing dataset. The most important variable was prednisolone, followed by lower age, mesalazine, budesonide, and ferric iron. Conclusions: In summary, this study reveals the advantages of ML-based models in predicting biologic therapy in IBD patients based on pre-treatment and demographic variables. There is a need for further studies in this regard that take into account individual patient characteristics, i.e., genetics and gut microbiota, to adequately address the challenges of finding optimal treatment strategies for patients with IBD. Full article
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18 pages, 1423 KiB  
Article
Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease
by Ruben Y. Gabriëls, Arno R. Bourgonje, Julius Z. H. von Martels, Tjasso Blokzijl, Rinse K. Weersma, Kevin Galinsky, Julius Juarez, Klaas Nico Faber, Gursah Kats-Ugurlu and Gerard Dijkstra
J. Clin. Med. 2022, 11(14), 4141; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11144141 - 16 Jul 2022
Cited by 1 | Viewed by 1729
Abstract
Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of [...] Read more.
Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy. Full article
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11 pages, 503 KiB  
Article
There Is a Differential Pattern in the Fatty Acid Profile in Children with CD Compared to Children with UC
by Justyna Kikut, Arleta Drozd, Małgorzata Mokrzycka, Urszula Grzybowska-Chlebowczyk, Maciej Ziętek and Małgorzata Szczuko
J. Clin. Med. 2022, 11(9), 2365; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11092365 - 23 Apr 2022
Cited by 4 | Viewed by 1470
Abstract
Background: Crohn’s disease (CD) and Ulcerative Colitis (UC) are classified as inflammatory bowel diseases (IBD). Currently, an increasing number of studies indicate that the metabolic consequences of IBD may include abnormalities in the fatty acid profile. The aim of this study was to [...] Read more.
Background: Crohn’s disease (CD) and Ulcerative Colitis (UC) are classified as inflammatory bowel diseases (IBD). Currently, an increasing number of studies indicate that the metabolic consequences of IBD may include abnormalities in the fatty acid profile. The aim of this study was to compare fatty acid concentrations in IBD in order to identify differences between CD and UC and differences between the phases of both diseases. Methods: Sixty-three adolescent patients with CD (n = 33) and UC (n = 30) aged 13.66 ± 2.67 and 14.15 ± 3.31, respectively, were enrolled in the study. Analysis was performed by gas chromatography. Results: A statistically significant higher concentration of vaccenic acid was observed in the total UC group relative to total CD. In remission CD relative to active CD, a significantly higher concentration of palmitic acid was shown. Whereas in active CD, significantly higher levels of linoleic acid were observed relative to remission. The UC group had significantly higher lauric acid and gamma-linoleic acid levels in active disease relative to remission. Conclusions: The identified differences between FA levels in UC and CD could potentially be involved in the course of both diseases. Full article
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14 pages, 555 KiB  
Article
Involvement of Proinflammatory Arachidonic Acid (ARA) Derivatives in Crohn’s Disease (CD) and Ulcerative Colitis (UC)
by Justyna Kikut, Małgorzata Mokrzycka, Arleta Drozd, Urszula Grzybowska-Chlebowczyk, Maciej Ziętek and Małgorzata Szczuko
J. Clin. Med. 2022, 11(7), 1861; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11071861 - 27 Mar 2022
Cited by 12 | Viewed by 2549
Abstract
Recently, an increase in the incidence of inflammatory bowel disease (IBD) has been observed, especially among children and adolescents. Currently, few studies focus on the differentiation of inflammation in IBD subunits, i.e., Crohn’s Disease (CD) and Ulcerative Colitis (UC). The aim of this [...] Read more.
Recently, an increase in the incidence of inflammatory bowel disease (IBD) has been observed, especially among children and adolescents. Currently, few studies focus on the differentiation of inflammation in IBD subunits, i.e., Crohn’s Disease (CD) and Ulcerative Colitis (UC). The aim of this study was to compare the concentrations of proinflammatory mediators of arachidonic acid (ARA) and linoleic acid (LA) in patients with CD (n = 34) and UC (n = 30), in order to identify differences in inflammation in both diseases and within the same entity, according to disease activity. Sixty-four adolescents with a mean age of 13.76 ± 2.69 and 14.15 ± 3.31, for CD and UC, respectively, were enrolled in the study. Biochemical analysis of ARA and LA derivatives was performed using a liquid chromatography. A trend was observed in the concentration of 15S-HETE (hydroxyeicosatetraenoic acids) in CD relative to UC. The active phase of both diseases showed a higher 15S-HETE concentration in active CD relative to active UC. Comparing patients with CD with active and inactive disease showed a trend of increased levels of thromboxane B2, leukotriene B4 and 9S-HODE (hydroxyoctadecadienoic acid) in the active versus the inactive disease. We also observed statistically significantly higher levels of 12S-HETE in inactive CD relative to active CD. In the UC group, on the other hand, statistically significantly higher levels of prostaglandin E2 and 16RS-HETE were observed in active UC relative to inactive UC. Moreover, significantly higher concentrations of LTX A4 5S, 6R were observed in inactive UC relative to the active phase. In conclusion, the present study indicated the activity of the 15-LOX pathway in CD. Further studies involving lipid mediators in patients with IBD may contribute to the development of new therapies for the treatment of IBD. The identification of differences in the course of inflammation may help to target therapy in CD and UC, and perhaps allow the introduction of an additional diagnostic marker between the two main IBD subtypes. Full article
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11 pages, 266 KiB  
Article
Bone Alterations in Inflammatory Bowel Diseases: Role of Osteoprotegerin
by Kateryna Priadko, Antimo Moretti, Giovanni Iolascon, Antonietta Gerarda Gravina, Agnese Miranda, Dolores Sgambato, Cristiana De Musis, Marco Romano and Francesca Gimigliano
J. Clin. Med. 2022, 11(7), 1840; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11071840 - 26 Mar 2022
Cited by 5 | Viewed by 1789
Abstract
Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to [...] Read more.
Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to inflammation, which involves the RANK-RANKL-Osteoprotegerin (OPG) pathway. This cross-sectional study investigates the role of serum OPG on bone health in IBD patients. In all patients, we carried out BMD measurements at the lumbar spine and femoral neck by the dual-energy X-ray absorptiometry (DXA), and evaluation of serum OPG, 25(OH)D, and PTH. We also divided all IBD patients into two groups: group 1 consisted of premenopausal women and men younger than 50 years old, while group 2 included postmenopausal women and men aged more than 50 years old. We enrolled 36 UC patients (51%), 34 CD patients (49%), and 70 healthy controls. IBD group mean age was 44 ± 17.3 years old, with a mean disease duration of 6 years. IBD patients had a mean value of OPG of 48.1 ± 26.64 pg/mL, while mean OPG in the control group was 61.35 ± 47.19 pg/mL (p < 0.05). In group 1, there was a correlation between BMD Z-scores at the lumbar spine and femoral neck and mean OPG levels in UC subjects (r = 0.47 and r = −0.21, respectively; p < 0.05), and only between Z-score at the lumbar spine and OPG level in the CD group (r = 0.83, p < 0.05). For the patients of group 2, we report a statistically significant correlation between T-score measured at the lumbar site in both UC and CD patients (r = −0.79 and r = 0.77, respectively; p < 0.05). In our study, we demonstrated serum OPG levels to be significantly decreased in IBD subjects compared to healthy age-matched individuals. However, according to our data, it seems that the measurement of serum OPG levels is not useful to better define metabolic bone disorders in IBD patients. Full article
9 pages, 832 KiB  
Article
Long-Term Risk of Colectomy in Patients with Severe Ulcerative Colitis Responding to Intravenous Corticosteroids or Infliximab
by Elena De Cristofaro, Silvia Salvatori, Irene Marafini, Francesca Zorzi, Norma Alfieri, Martina Musumeci, Emma Calabrese and Giovanni Monteleone
J. Clin. Med. 2022, 11(6), 1679; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11061679 - 18 Mar 2022
Cited by 7 | Viewed by 1831
Abstract
Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully [...] Read more.
Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX. Patients and methods: Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the “Tor Vergata University” hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy. Results: A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level <3 g/dL and colonic dilation >5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08–22.8, and OR 8.5, 95% CI: 1.23–58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor. Conclusions: A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX. Full article
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9 pages, 1588 KiB  
Article
Efficacy of a Preparation Based on Calcium Butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and Fructooligosaccharides in the Prevention of Relapse in Ulcerative Colitis: A Prospective Observational Study
by Gian Paolo Caviglia, Federico De Blasio, Marta Vernero, Angelo Armandi, Chiara Rosso, Giorgio Maria Saracco, Elisabetta Bugianesi, Marco Astegiano and Davide Giuseppe Ribaldone
J. Clin. Med. 2021, 10(21), 4961; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10214961 - 26 Oct 2021
Cited by 7 | Viewed by 2845
Abstract
Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of [...] Read more.
Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC. Full article
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8 pages, 485 KiB  
Article
Switching from Biosimilar to Biosimilar Adalimumab, Including Multiple Switching, in Crohn’s Disease: A Prospective Study
by Davide Giuseppe Ribaldone, Elisa Tribocco, Chiara Rosso, Angelo Armandi, Marta Vernero, Elisabetta Bugianesi, Marco Astegiano, Giorgio Maria Saracco and Gian Paolo Caviglia
J. Clin. Med. 2021, 10(15), 3387; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10153387 - 30 Jul 2021
Cited by 16 | Viewed by 2832
Abstract
No data are available regarding the safety and effectiveness of the biosimilar-to-biosimilar switch of adalimumab in any disease, and in particular in Crohn’s disease (CD). The aim of our study was to provide real world data on switching from biosimilar adalimumab to another [...] Read more.
No data are available regarding the safety and effectiveness of the biosimilar-to-biosimilar switch of adalimumab in any disease, and in particular in Crohn’s disease (CD). The aim of our study was to provide real world data on switching from biosimilar adalimumab to another biosimilar, including multiple switching. We conducted a prospective, single-centre observational study in which we consecutively recruited all CD patients who switched from adalimumab biosimilar ABP 501 to biosimilar SB5 from January to July 2021. Sixty-one patients were included in the final analysis, of whom 43/61 (70.5%) were multiple switches (Humira® → ABP 501 → SB5). After 6 months of follow up, 88.5% (54/61) of patients maintained SB5 on therapy. The success of the switch (defined as no systemic corticosteroids within 6 months, non-discontinuation of SB5, no dose escalation) was achieved by 82.0% (50/61) of patients. At multivariate analysis, C-reactive protein > 5 mg/L predicted switch failure (p = 0.03). Seven patients (11.5%) experienced side effects, compared to one patient (1.6%) in the 6 pre-switch months (p = 0.03). In conclusion, switching from biosimilar to biosimilar of adalimumab did not lead to signs of safety or loss of efficacy other than those already known in the literature for the class of drugs. Full article
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11 pages, 773 KiB  
Article
Hospitalisation for Drug Infusion Did Not Increase Levels of Anxiety and the Risk of Disease Relapse in Patients with Inflammatory Bowel Disease during COVID-19 Outbreak
by Lorenzo Bertani, Brigida Barberio, Domenico Tricò, Federico Zanzi, Daria Maniero, Linda Ceccarelli, Ilaria Marsilio, Francesca Coppini, Greta Lorenzon, Maria Gloria Mumolo, Fabiana Zingone, Francesco Costa and Edoardo Vincenzo Savarino
J. Clin. Med. 2021, 10(15), 3270; https://doi.org/10.3390/jcm10153270 - 24 Jul 2021
Cited by 1 | Viewed by 1568
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, immunomodulatory therapies and hospital admission were suspected to increase the risk of infection. Nevertheless, patients with inflammatory bowel diseases (IBD) treated with intravenous (i.v.) biologics had to move to hospitals for drug infusion. We investigated the [...] Read more.
During the coronavirus disease 2019 (COVID-19) pandemic, immunomodulatory therapies and hospital admission were suspected to increase the risk of infection. Nevertheless, patients with inflammatory bowel diseases (IBD) treated with intravenous (i.v.) biologics had to move to hospitals for drug infusion. We investigated the impact of hospitalisation in patients with IBD. We conducted a survey including consecutive IBD patients initially in clinical and biochemical remission treated with biologics at the end of the first lockdown period. Patients underwent the normally scheduled clinical visits, performed at hospital for i.v.-treated patients or at home for patients treated with s.c. drugs. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 12 questions, specifically related to COVID-19 and its implications. A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. No relapses were recorded in either group (hospitalized vs. non-hospitalized, p = ns), as well as which, COVID-19 infections were not demonstrated in patients in contact with people with suspected symptoms or directly experiencing them. The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs. 37.2 ± 2.8; p = 0.98). In patients treated with i.v. drugs receiving a televisit (n = 17), the rate of satisfaction with telemedicine (58.8%) was significantly lower compared with those treated with s.c. drugs (94.8%; p < 0.0005). Our results suggest that hospitalisation during the COVID-19 outbreak does not increase the risk of COVID-19 infection as well as the risk of IBD relapse; moreover, the similar levels of anxiety in both groups could confirm that there is no need to convert patients from i.v. to s.c. therapy. Full article
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Review

Jump to: Editorial, Research

22 pages, 1692 KiB  
Review
Comparative Effectiveness Research: A Roadmap to Sail the Seas of IBD Therapies
by Daniela Pugliese, Sara Onali, Giuseppe Privitera, Alessandro Armuzzi and Claudio Papi
J. Clin. Med. 2022, 11(22), 6717; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11226717 - 13 Nov 2022
Cited by 2 | Viewed by 1952
Abstract
The drug pipeline for the treatment of inflammatory bowel disease (IBD) has dramatically expanded over the last two decades, and it is expected to further grow in the upcoming years with the introduction of new agents with different mechanisms of action. However, such [...] Read more.
The drug pipeline for the treatment of inflammatory bowel disease (IBD) has dramatically expanded over the last two decades, and it is expected to further grow in the upcoming years with the introduction of new agents with different mechanisms of action. However, such an increase of therapeutic options needs to be paralleled with an appropriate development of research to help physicians in the decision-making process when choosing which drug to prescribe. On the population level, comparative effectiveness research (CER) is intended to explore and identify relevant differences—in terms of both efficacy and safety outcomes—amongst different therapeutic regimens and/or strategies, in order to find the correct placement for each treatment in the therapeutic algorithm. CER revolves around three cornerstones: network meta-analyses, head-to-head trials and real-world studies, each of which has specific pros and cons, and can therefore offer answers to different questions. In this review, we aim to provide an overview on the methodological features specific to each of these research approaches, as well as to illustrate the main findings coming from CER on IBD target therapies (i.e., biologics and small molecules) and to discuss their appropriate interpretation. Full article
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27 pages, 823 KiB  
Review
The Optimal Management of Fistulizing Crohn’s Disease: Evidence beyond Randomized Clinical Trials
by Panu Wetwittayakhlang, Alex Al Khoury, Gustavo Drügg Hahn and Peter Laszlo Lakatos
J. Clin. Med. 2022, 11(11), 3045; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11113045 - 28 May 2022
Cited by 9 | Viewed by 7093
Abstract
Fistulizing Crohn’s disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require [...] Read more.
Fistulizing Crohn’s disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30–50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD. Full article
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25 pages, 5348 KiB  
Review
Inflammatory Bowel Disease and Neutrophil–Lymphocyte Ratio: A Systematic Scoping Review
by Blake O. Langley, Sara E. Guedry, Joshua Z. Goldenberg, Douglas A. Hanes, Jennifer A. Beardsley and Jennifer Joan Ryan
J. Clin. Med. 2021, 10(18), 4219; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10184219 - 17 Sep 2021
Cited by 22 | Viewed by 5970
Abstract
Neutrophil–lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation [...] Read more.
Neutrophil–lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD. Full article
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14 pages, 2402 KiB  
Review
Faecal Calprotectin in Assessment of Mucosal Healing in Adults with Inflammatory Bowel Disease: A Meta-Analysis
by Mariusz A. Bromke, Katarzyna Neubauer, Radosław Kempiński and Małgorzata Krzystek-Korpacka
J. Clin. Med. 2021, 10(10), 2203; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10102203 - 19 May 2021
Cited by 16 | Viewed by 2652
Abstract
Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly [...] Read more.
Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease. Full article
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