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Journal of Crohn's & Colitis Oct 2020We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD].
OBJECTIVE
We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD].
METHODS
We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.
RESULTS
We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone.
CONCLUSIONS
We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
PubMed: 33026087
DOI: 10.1093/ecco-jcc/jjaa161 -
Gastroenterology Jun 2021The incidence and prevalence of Crohn's disease (CD) is rising globally. Patients with moderate to severe CD are at high risk for needing surgery and hospitalization and... (Review)
Review
The incidence and prevalence of Crohn's disease (CD) is rising globally. Patients with moderate to severe CD are at high risk for needing surgery and hospitalization and for developing disease-related complications, corticosteroid dependence, and serious infections. Optimal management of outpatients with moderate to severe luminal and/or fistulizing (including perianal) CD often requires the use of immunomodulator (thiopurines, methotrexate) and/or biologic therapies, including tumor necrosis factor-α antagonists, vedolizumab, or ustekinumab, either as monotherapy or in combination (with immunomodulators) to mitigate these risks. Decisions about optimal drug therapy in moderate to severe CD are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Since the last iteration of these guidelines published in 2013, significant advances have been made in the field, including the regulatory approval of 2 new biologic agents, vedolizumab and ustekinumab. Therefore, the American Gastroenterological Association prioritized updating clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The review addressed the following focused questions (in adult outpatients with moderate to severe luminal CD): overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to tumor necrosis factor-α antagonists, comparative efficacy and safety of biologic monotherapy vs combination therapy with immunomodulators, comparative efficacy of a top-down (upfront use of biologics and/or immunomodulator therapy) vs step-up treatment strategy (acceleration to biologic and/or immunomodulator therapy only after failure of mesalamine), and the role of corticosteroids and mesalamine for induction and/or maintenance of remission. Finally, in adult outpatients with moderate to severe fistulizing CD, this review addressed the efficacy of pharmacologic interventions for achieving fistula and the role of adjunctive antibiotics without clear evidence of active infection.
Topics: Adult; Crohn Disease; Decision Support Systems, Clinical; Disease Management; Female; Gastroenterology; Humans; Male; Practice Guidelines as Topic; Rectal Fistula; Severity of Illness Index; Societies, Medical
PubMed: 34051985
DOI: 10.1053/j.gastro.2021.04.023 -
World Journal of Gastroenterology Jul 2021Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and... (Review)
Review
Perianal Crohn's disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn's disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn's disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn's disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn's disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.
Topics: Crohn Disease; Humans; Infliximab; Quality of Life; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34321838
DOI: 10.3748/wjg.v27.i25.3693 -
Clinics in Colon and Rectal Surgery Jul 2022Mesenteric panniculitis (MP) is the preferred nomenclature for a continuum of inflammatory diseases of the mesentery. The diagnosis of MP is often based on the... (Review)
Review
Mesenteric panniculitis (MP) is the preferred nomenclature for a continuum of inflammatory diseases of the mesentery. The diagnosis of MP is often based on the appearance of a mass-like structure at the root of the mesentery. Characteristic histology includes focal fat necrosis, chronic inflammation, and sometimes mesenteric fibrosis. At present, robust literature related to diagnosis and management of MP are limited. MP is postulated to be an immune-mediated chronic inflammatory and/or a paraneoplastic disease. A personal or family history of other autoimmune diseases is commonly apparent. Several inciting events have been identified that possibly act as triggers in the development of the disease. Trauma, abdominal surgery, infection, and various cancers have been associated with mesenteric panniculitis. There are several diagnostic and histologic criteria that aid in making the diagnosis of MP. The differential diagnosis for a mesenteric mass includes neoplastic disease, and a biopsy may be indicated to rule out other conditions. While cases of MP with a short duration of symptoms, or spontaneously regression may occur, some patients experience prolonged periods of pain, fever, and alterations in bowel habit, causing significant morbidity. A variety of medical therapies have been suggested for MP. Only two, thalidomide and low-dose naltrexone, have been prospectively evaluated. For patients with chronic MP, good responses to prolonged corticosteroid treatment have been reported. Novel therapies include thalidomide and low-dose naltrexone. Hormonal and immunomodulatory therapies are also used based on small case series, but these treatments may have significant side effects. Surgical intervention is not curative and is avoided except for relief of focal bowel obstruction secondary to fibrotic forms of the disease.
PubMed: 35966977
DOI: 10.1055/s-0042-1743588 -
Metabolites Jan 2023Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two... (Review)
Review
Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.
PubMed: 36677021
DOI: 10.3390/metabo13010096 -
Nutrients Jun 2021Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains... (Randomized Controlled Trial)
Randomized Controlled Trial
Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of strain Shirota (LcS), formerly strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (10 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups ( < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial , and levels and decreased the bacterial levels related to mental illness, such as , and Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups ( < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period ( < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
Topics: Adult; Animals; Constipation; Cultured Milk Products; Depression; Double-Blind Method; Feces; Female; Gastrointestinal Microbiome; Humans; Lacticaseibacillus paracasei; Male; Middle Aged; Probiotics; Treatment Outcome
PubMed: 34209804
DOI: 10.3390/nu13072238 -
Clinics in Colon and Rectal Surgery Nov 2022Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the gold standard surgical treatment for the majority (∼90%) of ulcerative colitis (UC) patients. In... (Review)
Review
Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is the gold standard surgical treatment for the majority (∼90%) of ulcerative colitis (UC) patients. In cases of carefully selected Crohn's colitis patients without small bowel or perianal involvement an "intentional IPAA" may be a viable option for disease resection and restoration of intestinal continuity. More commonly, Crohn's is incidentally found either in the resection specimen or, more commonly, when inflammatory complications subsequently arise after pouch construction for UC or indeterminate colitis. These incidental Crohn's pouches may be diagnosed early or late period post-IPAA. Crohn's may manifest within the pouch, in the proximal small bowel, and/or distally in the rectal cuff or anus. Like intestinal Crohn's, Crohn's disease of the pouch may be of an inflammatory, fibrostenosing, or fistulizing phenotype. Treatment depends on the phenotype and includes medical treatment, most commonly in the form of tumor necrosis factor inhibitor medications; however, the newer small molecules offer a potential treatment for these patients. Surgery first entails treating the sequelae of Crohn's and is typically staged. In up to 60% of Crohn's pouches, particularly in fistulizing disease and/or recalcitrant perianal disease, the pouch fails and must be defunctioned or excised. In patients with Crohn's pouches in situ long term, outcomes including quality of life are comparable to patients who underwent IPAA for UC.
PubMed: 36591396
DOI: 10.1055/s-0042-1758139 -
Journal of Clinical Medicine Aug 2023Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality... (Review)
Review
Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn's disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn's disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn's, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn's disease.
PubMed: 37685662
DOI: 10.3390/jcm12175595 -
EClinicalMedicine Mar 2023Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but...
BACKGROUND
Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.
FINDINGS
The systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.
INTERPRETATION
In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
FUNDING
None.
PubMed: 36864986
DOI: 10.1016/j.eclinm.2023.101866