Genetic factors modifying response to glucocorticoid treatment in chronic pediatric inflammatory bowel diseases

2015 ◽  
Vol 6 (3) ◽  
pp. 91-97 ◽  
Author(s):  
Nadezhda Konstantinovna Zaletova ◽  
Lubov Pavlovna Vostokova ◽  
Alexey Borisovich Chukhlovin ◽  
Elena Alexandrovna Kornienko ◽  
Anna Timofeevna Tretjak
Keyword(s):  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Genetic Factors ◽  
Receptor Expression ◽  
High Dose ◽  
Clinical Effects ◽  
Gene Variants ◽  
Cell Functions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The article concerns genetic factors that determine efficiency of steroid treatment for chronic inflammatory bowel diseases (IBD) in children, focused, mostly, on Crohn disease and nonspecific ulcerative colitis. Their incidence comprises 5 to 15 per 100 000 children and adolescents. In acute phase, therapy of these diseases is based on salicylates and glucocorticoids which regulate cytokine network and immune cell functions. Application of high-dose glucocorticoids (GCs) exerts а sufficient immunosuppressive action. These effects are performed via specific GC receptors in the target cell populations. Hence, numbers and functionality of GC receptors are important for clinical response to GC treatment. The aim of this review is discern major genetic effects upon functioning of glucocorticoid receptors. Here we discuss effects of N363S, ER22/23EK, and NR3C1 variants, the most known GC functional gene polymorphisms. These gene variants are often associated with altered GC gene expression in individual cases of IBD. Moreover, some other gene variants are able to modulate the GC receptor expression, thus making it difficult to assess genetic predisposition to altered clinical response to glucocorticoids. Hence, the regulatory effects of single gene variants upon GC receptors may not show direct correlations with clinical effects of the drug. Therefore, we propose an immediate way to assess the gene activity, i. e., quantitative analysis of the gene transcription (mRNA detection) in the patients’ cells before and during glucocorticoid therapy, presuming further application of this parameter as a predictive marker for evaluation of optimal therapeutic response in the individual IBD patients.

scholarly journals Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases

2020 ◽  
Vol 9 (5) ◽  
pp. 1323 ◽  
Author(s):  
Lorenzo Bertani ◽  
Gian Paolo Caviglia ◽  
Luca Antonioli ◽  
Rinaldo Pellicano ◽  
Sharmila Fagoonee ◽  
...  
Keyword(s):  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Area Under The Curve ◽  
Clinical Role ◽  
Faecal Calprotectin ◽  
Prediction Ability ◽  
Prospective Multicentre Study ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Vedolizumab, a monoclonal antibody directed against integrin α4β7, is an effective treatment for inflammatory bowel diseases. However, a significant number of patients do not achieve steroid-free clinical remission in the first year of treatment. An early identification of these patients is one of the most important challenges for clinicians and offers the possibility of therapeutic optimization in order to personalize biological therapy. The aim of our study was to test the prediction ability of interleukin (IL)-6 and -8 of clinical response after 12 months of therapy with vedolizumab (T2). We performed a prospective, multicentre study in patients affected by inflammatory bowel disease by analysing cytokines level before starting vedolizumab (T0) and after 10 weeks of therapy (T1). In the overall cohort (n = 54), IL-8 decrease > 2.6 pg/mL in the first 10 weeks of therapy was able to predict clinical response (area under the curve (AUC) = 0.70, sensitivity = 66%, specificity = 75%, p = 0.010), negative C-reactive protein (CRP) (AUC = 0.71, sensitivity = 64%, specificity = 80%, p = 0.009) and calprotectin < 250 mg/kg (AUC = 0.69, sensitivity = 64%, specificity = 78%, p = 0.030) after 44 weeks of therapy. In patients with ulcerative colitis (n = 40), baseline IL-8 values > 8.6 pg/mL and a decrease of IL-6 values > 0.4 pg/mL from T0 to T1 were significant and independent predictors of clinical response after 12 months of vedolizumab therapy (odds ratio (OR) = 6.96, 95% CI 1.27–38.22, p = 0.026 and OR = 7.29, 95% CI 1.42–37.50, p = 0.017, respectively). In patients with Crohn’s disease (n = 14), baseline IL-8 values > 8.6 pg/mL and baseline IL-6 values > 1.6 pg/mL allowed the identification of patients achieving negative CRP at T2 (AUC = 0.75, sensitivity = 74%, specificity = 76%, p < 0.001) and patients with faecal calprotectin values < 250 mg/kg at T2 (AUC = 0.71, sensitivity = 78%, specificity = 63%, p = 0.004). In conclusion, our study highlights a potential clinical role of serum cytokine levels for the prediction of clinical and biochemical steroid-free response in patients treated with vedolizumab.

P058 LOW DOSE METHOTREXATE HAS SIMILAR OUTCOMES AS HIGH-DOSE METHOTREXATE IN COMBINATION WITH ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASES

2019 ◽  
Vol 25 (Supplement_1) ◽  
pp. S28-S28
Author(s):  
Nynke Z Borren ◽  
Jay Luther ◽  
Francis P Colizzo ◽  
John J Garber ◽  
Hamed Khalili ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Low Dose ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Genetic factors in pathogenesis, course and treatment of inflammatory bowel diseases

2015 ◽  
Vol 69 ◽  
pp. 335-344 ◽  
Author(s):  
Hubert Zatorski ◽  
Maciej Sałaga ◽  
Marta Zielińska ◽  
Jakub Fichna
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Genetic Factors ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice

2020 ◽  
Vol 92 (2) ◽  
pp. 67-73
Author(s):  
M. V. Shapina ◽  
B. A. Nanaeva
Keyword(s):  
Clinical Practice ◽  
Clinical Response ◽  
Inflammatory Bowel Diseases ◽  
Clinical Remission ◽  
Line Therapy ◽  
Steroid Dependent ◽  
Endoscopic Remission ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Real Clinical Practice

Vedolizumab is currently the only selective biological drug for the treatment of inflammatory bowel diseases (IBD). Its effectiveness and safety has been shown in clinical trials. This article presents the experience of using vedolizumab in real clinical practice in patients with various forms of ulcerative colitis (UC) and Crohns disease (CD). Materials and methods.96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated). Results.After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months 62.5%, endoscopic remission 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%). Conclusions.Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

The role of STAT4 gene variants on the susceptibility and phenotype of inflammatory bowel diseases

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
J Glas ◽  
J Seiderer ◽  
M Nagy ◽  
B Göke ◽  
T Ochsenkühn ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Gene Variants ◽  
Bowel Diseases ◽  
Inflammatory Bowel
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