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World Journal of Gastroenterology Apr 2024The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical... (Review)
Review
The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical gastroenterologist. It seems to be no exaggeration to say that in these patients, not only the scientific background of the gastroenterologist is tested, but also the abundance of "gifts" that he should possess (insight, intuition, determination, ability to take initiative, ) for the successful outcome of the treatment. In daily clinical practice, depending on the severity of the attack, IBD is treated with one or a combination of two or more pharmaceutical agents. These combinations include not only the first-line drugs (., mesalazine, corticosteroids, antibiotics, ) but also second- and third-line drugs (immunosuppressants and biologic agents). It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied. Therefore, a part of these patients are going to surgery. In recent years, several small-size clinical studies, reviews, and case reports have been published combining not only biological agents with other drugs ( immunosuppressants or corticosteroids) but also the combination of two biological agents simultaneously, especially in severe cases. In our opinion, it is at least a strange (and largely unexplained) fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few. As mentioned above, there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations. The appropriate dosage, the duration of the administration, the suitable timing for checking the clinical and laboratory outcome, as well as the treatment side-effects, should be the subject of intense clinical research shortly. In this editorial, we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients. We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
Topics: Humans; Drug Therapy, Combination; Immunosuppressive Agents; Treatment Outcome; Inflammatory Bowel Diseases; Adrenal Cortex Hormones; Gastrointestinal Agents; Severity of Illness Index; Anti-Bacterial Agents; Biological Products
PubMed: 38681984
DOI: 10.3748/wjg.v30.i15.2068 -
Medicine Apr 2024This article presents a complex case of refractory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammatory bowel disease (IBD) and outlines its...
RATIONALE
This article presents a complex case of refractory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammatory bowel disease (IBD) and outlines its diagnostic and therapeutic challenges. Considering inadequate responses to conventional and steroid treatments, the potential efficacy of intravenous immunoglobulin is explored.
PATIENT CONCERNS
The patient, an elderly individual, experienced short-term fever and sore throat after encountering the coronavirus disease 2019 pandemic. Despite receiving a 3-dose inactivated SARS-CoV-2 vaccine, the patient tested positive for the viral antigen and developed worsening symptoms, including diarrhea and recurrent fever. Initial antibiotic treatment for bacterial enteritis proved ineffective.
DIAGNOSES
Further evaluation, including endoscopy and pathology, confirmed the diagnosis of IBD with concurrent multisystem inflammatory syndrome (MIS) in adults, as evidenced by tachycardia and elevated inflammatory markers.
INTERVENTIONS
Following unsuccessful treatment with mesalazine, probiotics, corticosteroids, and supportive care, the patient underwent lower-dose intravenous immunoglobulin therapy.
OUTCOMES
The patient experienced symptom improvement, with resolution of fever, diarrhea, and inflammation. At the 30-day follow-up, the patient remained afebrile, without diarrhea, and exhibited favorable mental status.
LESSONS
Elderly individuals infected with SARS-CoV-2 may develop severe systemic inflammatory responses. The patients in this report predominantly presented with IBD following SARS-CoV-2 infection, accompanied by MIS. Favorable clinical outcomes were achieved following lower-dose intravenous immunoglobulin immunotherapy, which demonstrated superior efficacy compared to glucocorticoids in managing such conditions. Future research should prioritize investigating immunotherapy application strategies in IBD and MIS. Notably, the significant clinical improvement observed with lower-dose intravenous immunoglobulin administration could optimize the utilization of this limited medical resource.
Topics: Humans; Male; COVID-19; Immunoglobulins, Intravenous; Inflammatory Bowel Diseases; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Aged, 80 and over
PubMed: 38669420
DOI: 10.1097/MD.0000000000037888 -
JAAPA : Official Journal of the... May 2024Traditionally, medical providers have used the step-up approach to manage patients with Crohn disease, starting with 5-aminosalicylic acid derivatives, progressing to...
Traditionally, medical providers have used the step-up approach to manage patients with Crohn disease, starting with 5-aminosalicylic acid derivatives, progressing to corticosteroids, and eventually to immunomodulators and biologics. However, a new top-down approach focuses on early and aggressive therapy with biologics and immunomodulators to reduce the rate of mucosal and intestinal damage. This article describes early and aggressive biologic and immunomodulator therapies and new therapeutic parameters compared with traditional step-up treatment for patients with Crohn disease.
Topics: Humans; Adrenal Cortex Hormones; Biological Products; Crohn Disease; Immunologic Factors; Immunomodulating Agents; Mesalamine
PubMed: 38662903
DOI: 10.1097/01.JAA.0000000000000013 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Apr 2024To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran...
OBJECTIVES
To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC.
METHODS
Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1β) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence.
RESULTS
Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (<0.01), increased DAI score and spleen index (<0.01), elevated serum IL-18 and IL-1β levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (<0.05), reduced DAI scores and spleen indexes (<0.05), decreased serum IL-18 and IL-1β levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (<0.05). There were no significant differences in the above indexes between the medication group and the EA group (>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration.
CONCLUSIONS
EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.
Topics: Rats; Male; Animals; Colitis, Ulcerative; Inflammasomes; Interleukin-18; Rats, Sprague-Dawley; NLR Family, Pyrin Domain-Containing 3 Protein; Electroacupuncture; Occludin; Body Weight; Caspases
PubMed: 38621732
DOI: 10.13703/j.0255-2930.20230716-k0001 -
Advances in Therapy Jun 2024Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed... (Observational Study)
Observational Study
INTRODUCTION
Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy.
METHODS
This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed.
RESULTS
At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period 2013-2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678 euro (€), for UC and €6925 for CD.
CONCLUSION
This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Italy; Male; Female; Retrospective Studies; Middle Aged; Adult; Aged; Incidence; Health Resources; Health Care Costs
PubMed: 38619721
DOI: 10.1007/s12325-024-02840-x -
Journal of Controlled Release :... May 2024Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site....
Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.
Topics: Mesalamine; Humans; Colon; Gastrointestinal Microbiome; Anti-Inflammatory Agents, Non-Steroidal; Sulfasalazine; Prodrugs; Drug Delivery Systems; Colitis, Ulcerative; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Drug Liberation
PubMed: 38599548
DOI: 10.1016/j.jconrel.2024.04.016 -
Clinical Case Reports Apr 2024This case report describes the clinical course of a 64-year-old male with intermittent abdominal pain attributed to recurrent ulcers at the appendiceal orifice. Initial...
This case report describes the clinical course of a 64-year-old male with intermittent abdominal pain attributed to recurrent ulcers at the appendiceal orifice. Initial investigations in November 2019 revealed chronic gastritis and ulcers at the appendiceal orifice, prompting consideration of ulcerative colitis (UC). The patient responded well to mesalazine therapy, experiencing relief from symptoms and improved colonoscopy findings in May 2020. Despite discontinuing medication, a recurrence of symptoms in August 2021 led to a repeat colonoscopy showing renewed ulcers. Mesalazine was reinstated, resulting in symptom resolution and improved colonoscopy findings by December 2021. However, in May 2023, a subsequent recurrence of abdominal pain and colonoscopy-confirmed mucosal changes at the appendiceal orifice prompted reintroduction of mesalazine. The patient remains under regular monitoring on mesalazine therapy. This case highlights the challenges in managing recurrent appendiceal ulcers and the importance of long-term therapeutic vigilance in suspected UC cases.
PubMed: 38595965
DOI: 10.1002/ccr3.8573 -
Journal of Gastroenterology Jun 2024This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world...
BACKGROUND
This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.
METHODS
A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.
RESULTS
Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.
CONCLUSIONS
NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Topics: Humans; Pyrophosphatases; Female; Male; Retrospective Studies; Adult; Middle Aged; Mercaptopurine; Genotype; Inflammatory Bowel Diseases; Japan; Azathioprine; Young Adult; Aged; Immunosuppressive Agents; Adolescent; Risk Factors; Codon; Nudix Hydrolases
PubMed: 38589597
DOI: 10.1007/s00535-024-02099-7 -
International Journal of Pharmaceutics Apr 2024
Corrigendum to "The effect of esomeprazole on the upper GI tract release and systemic absorption of mesalazine from colon targeted formulations" [Int. J. Pharm. 619 (2022) 121701].
PubMed: 38584003
DOI: 10.1016/j.ijpharm.2024.124087