Prediction of clinical effects of infliximab administered for inflammatory bowel disease based on pharmacokinetic and pharmacodynamic modeling

Exclusive Enteral Nutrition (EEN) is the first-line treatment in children with Crohn’s disease (CD) for induction of remission. However, the mode of action remains conjectural. The aim of this study was to investigate whether the effect of EEN is paralleled by changes in the mucosal cytokine profiles (MCP). Twelve children with new onset inflammatory bowel disease (IBD) received induction treatment with a polymeric EEN. We assessed clinical, endoscopic and histologic scoring before and after EEN. Twelve colonic cytokines were analyzed by Polymerase Chain Reaction (PCR) in six of the IBD patients at onset and after EEN as well as in six non-IBD control children at the diagnostic colonoscopy. Twelve children completed 6 weeks of EEN, except from one child who completed 4 weeks. At the control colonoscopy, 83% were in complete clinical remission. Changes were found in the MCPs of individual patients after EEN. In particular, children with IBD showed significantly higher values of Interleukin (IL)-12β (p = 0.008) and IL-23α (p = 0.02) compared to non-IBD controls at the diagnostic colonoscopy. Furthermore, an overall change in proinflammatory cytokines was noted in the IBD-group after treatment. Further studies are warranted to understand the role of EEN in MCP.

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Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis

European Journal of Nutrition ◽

10.1007/s00394-021-02503-5 ◽

2021 ◽

Author(s):

Xiao-Feng Zhang ◽

Xiao-Xian Guan ◽

Yu-Jun Tang ◽

Jin-Feng Sun ◽

Xiao-Kai Wang ◽

...

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Meta Analysis ◽

Clinical Effects ◽

Inflammatory Bowel

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Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants

Genes ◽

10.3390/genes10040277 ◽

2019 ◽

Vol 10 (4) ◽

pp. 277 ◽

Cited By ~ 1

Author(s):

Marianna Lucafò ◽

Gabriele Stocco ◽

Stefano Martelossi ◽

Diego Favretto ◽

Raffaella Franca ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Efficacy ◽

Bowel Disease ◽

Genetic Variants ◽

Young Patients ◽

Linear Mixed Effect Model ◽

Clinical Effects ◽

Dose Ratio ◽

Mixed Effect ◽

Inflammatory Bowel

The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Candidate genetic variants (TPMT rs1142345, rs1800460, rs1800462, GSTA1 rs3957357, GSTM1, and GSTT1 deletion) were determined by polymerase chain reaction (PCR) assays and pyrosequencing. Statistical analysis was performed using linear mixed effects models for the association between the candidate variants and the pharmacological variables (azathioprine doses and metabolites). Azathioprine metabolites were measured in 257 samples (median 2 per patient, inter-quartile range IQR 1-3). Clinical efficacy at the first evaluation available resulted better in ulcerative colitis than in Crohn’s disease patients (88.0% versus 52.5% responders, p = 0.0003, linear mixed effect model, LME). TGN concentration and the ratio TGN/dose at the first evaluation were significantly higher in responder. TPMT rs1142345 variant (4.8% of patients) was associated with increased TGN (LME p = 0.0042), TGN/dose ratio (LME p < 0.0001), decreased azathioprine dose (LME p = 0.0087), and MMPN (LME p = 0.0011). GSTM1 deletion (58.1% of patients) was associated with a 18.5% decrease in TGN/dose ratio and 30% decrease in clinical efficacy. GSTA1 variant (12.8% of patients) showed a trend (p = 0.049, LME) for an association with decreased clinical efficacy; however, no significant effect on azathioprine pharmacokinetics could be detected. In conclusion, GSTs variants are associated with azathioprine efficacy and pharmacokinetics.

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Clinical Effects of Short-Term Oral Budesonide on the Hypothalamic-Pituitary-Adrenal Axis in Dogs With Inflammatory Bowel Disease

Journal of the American Animal Hospital Association ◽

10.5326/0400120 ◽

2004 ◽

Vol 40 (2) ◽

pp. 120-123 ◽

Cited By ~ 18

Author(s):

Joshua W. Tumulty ◽

John D. Broussard ◽

Jörg M. Steiner ◽

Mark E. Peterson ◽

David A. Williams

Keyword(s):

Inflammatory Bowel Disease ◽

Specific Gravity ◽

Hpa Axis ◽

Bowel Disease ◽

Serum Alkaline Phosphatase ◽

Urine Specific Gravity ◽

Clinical Effects ◽

Hypothalamic Pituitary Adrenal ◽

Oral Preparation ◽

Inflammatory Bowel

Six dogs were entered into a 30-day, prospective, nonrandomized, uncontrolled clinical trial evaluating the effects of an oral preparation of budesonide on the hypothalamic-pituitary-adrenal (HPA) axis during therapeutic management of active inflammatory bowel disease. Oral budesonide, at a dose of 3 mg/m2, was administered once daily. Upon entry and completion of the trial, serum basal cortisol, adrenocorticotropic (ACTH)-stimulated cortisol, endogenous ACTH concentration, serum alkaline phosphatase (SAP) activity, and urine specific gravity were evaluated, as well as owner assessment of glucocorticoid-associated side effects. Significant suppression of the HPA axis occurred. No significant differences in SAP activity, urine specific gravity, or owner-subjective assessments were detected.

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Lifestyle Issues in Inflammatory Bowel Disease – Smoking

Canadian Journal of Gastroenterology ◽

10.1155/1994/369127 ◽

1994 ◽

Vol 8 (7) ◽

pp. 422-427 ◽

Cited By ~ 2

Author(s):

Cecilia Benoni

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Protective Effect ◽

Bowel Disease ◽

Clinical Course ◽

Clinical Effects ◽

Increased Risk ◽

Inflammatory Bowel

During the pa t decade, smoking habit has been identified as a major exogenous factor in inflammatory bowel disease (IBD). It is associated not only with the development of the disease but al o with the clinical course in established disease. IBD combines absolute opposites as smoking is associated with Crohn’s disease and nonsmoking or former smoking with ulcerative colitis. The first reports of a negative association between smoking and ulcerative colitis were based on independent, clinical observations; from those studies a positive association was found between smoking and Crohn’s disease. Epidemiological studies that followed consistently showed that smokers have a reduced risk of ulcerative colitis and an increased risk of Crohn’s disease and that exsmokers have an increased risk of ulcerative colitis. In ulcerative colitis, but not in Crohn’s disease, a dose-response pattern has been demonstrated. Changes in clinical course, in disease severity and extension, and in recurrence rate indicate substantial clinical effects of smoking with a protective effect of smoking in ulcerative colitis and an aggravating effect in Crohn’s disease. There are also indications of smoking’s effects on changes in IBD epidemiology and sex distribution. The biological explanation to the finding is unknown. Smoking may aggravate Crohn’s disease by vascular effects. Theories on the protective effect in ulcerative colitis include effects on immune and inflammatory response, on mucus and on intestinal permeability. Possibly, beneficial effects in ulcerative colitis are exerted by nicotine but further studies are needed. Due to overall negative effects of smoking, IBD patients should not smoke. It seems, however, reasonable to give individual advice in patients with ulcerative colitis who have experienced a beneficial effect of ·making considering both current health status and life situation.

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Evaluation of the Clinical Effects and Frequency of MEFV Gene Mutation in Patients with Inflammatory Bowel Disease

Gastroenterology Research and Practice ◽

10.1155/2021/5538150 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

S. Sahin ◽

D. Gulec ◽

S. Günay ◽

C. Cekic

Keyword(s):

Inflammatory Bowel Disease ◽

Gene Mutation ◽

Bowel Disease ◽

Mefv Gene ◽

Gene Mutations ◽

Clinical Effects ◽

Mediterranean Fever ◽

Inflammatory Bowel ◽

The Relationship ◽

Mefv Gene Mutation

Background. The clinical and pathological features of inflammatory bowel disease (IBD) and Familial Mediterranean Fever (FMF) are similar. Objective. Here, the frequency of Mediterranean Fever (MEFV) gene mutation and its effect on the outcome of IBD were evaluated. Methods. DNA sequence analysis detected the variants on the MEFV gene in patients with IBD. The relationship between mutations and the need for steroids, immunomodulators, biologics, and surgery was assessed. Results. We evaluated 100 patients with IBD (55 with ulcerative colitis (UC) and 45 with Crohn’s disease (CD)) and 60 healthy individuals as controls. The frequency of MEFV gene mutation was 26.7% ( n = 12 ) and 14.5% ( n = 8 ) for UC and CD, respectively. No relationship was found between MEFV gene mutation and the need for steroids, immunomodulators, and biologics ( p = 0.446 ; p = 0.708 ; p > 0.999 , resp.); however, in UC, the need for surgery in those with mutation ( p = 0.018 ) and E148Q mutation alone was significant ( p = 0.037 ). Conclusion. The rate of MEFV gene mutations was high in patients with UC who required surgery. These patients have frequent and severe attacks, indicating that the mutations are related to disease severity. MEFV mutation as a modifier factor of IBD should be considered.

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