P.14.3 CORRELATION BETWEEN CLINICAL RESPONSE AND ANEMIA RESOLUTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES TREATED WITH ANTI-TNF INHIBITORS

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.

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

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.02.000528 ◽

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.

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Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i35.6385 ◽

2017 ◽

Vol 23 (35) ◽

pp. 6385-6402 ◽

Cited By ~ 16

Author(s):

Abhinav Vasudevan ◽

Peter R Gibson ◽

Daniel R van Langenberg

Keyword(s):

Clinical Response ◽

Inflammatory Bowel Diseases ◽

Bowel Diseases ◽

Inflammatory Bowel

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On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Journal of Clinical Medicine ◽

10.3390/jcm9030800 ◽

2020 ◽

Vol 9 (3) ◽

pp. 800 ◽

Cited By ~ 6

Author(s):

Gian Caviglia ◽

Chiara Rosso ◽

Francesco Stalla ◽

Martina Rizzo ◽

Alessandro Massano ◽

...

Keyword(s):

Clinical Response ◽

Inflammatory Bowel Diseases ◽

Biologic Therapy ◽

Multivariate Logistic Regression Analysis ◽

Response To Treatment ◽

Control Group ◽

Biologic Treatment ◽

Necrosis Factor Alpha ◽

Bowel Diseases ◽

Inflammatory Bowel

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

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Immunological Variables Associated With Clinical and Endoscopic Response to Vedolizumab in Patients With Inflammatory Bowel Diseases

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa035 ◽

2020 ◽

Vol 14 (9) ◽

pp. 1190-1201 ◽

Cited By ~ 2

Author(s):

Marina Coletta ◽

Moira Paroni ◽

Maria Francesca Alvisi ◽

Matilde De Luca ◽

Eliana Rulli ◽

...

Keyword(s):

Clinical Response ◽

Lamina Propria ◽

Inflammatory Bowel Diseases ◽

Peripheral Blood ◽

Clinical Remission ◽

Multivariable Analysis ◽

Response To Treatment ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Baseline Levels

Abstract Background and Aims Vedolizumab [VDZ] is a monoclonal antibody directed against the α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases [IBD]. This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis [UC] and Crohn’s disease [CD]. Methods This is a phase IV explorative prospective interventional trial. IBD patients received open-label VDZ at Weeks 0, 2, 6, and 14. Patients with a clinical response at Week 14 were maintained with VDZ up to Week 54. At Weeks 0 and 14, their peripheral blood was obtained and endoscopy with biopsies was performed. The Week 14 clinical response and remission, Week 54 clinical remission, and Week 14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors, and α4β7 heterodimer in peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators was assessed in sera at baseline and at Week 14 by 45-plex. Results A total of 38 IBD patients [20 UC, 18 CD] were included in the study. At Week 14, the clinical response and remission rates were 87% and 66%, respectively. Higher baseline levels of circulating memory Th1 cells were strongly associated with clinical response at Week 14 [p = 0.0001], whereas reduced baseline levels of lamina propria memory Th17 and Th1/17 cells were associated with endoscopic response. Immunological clusters were found to be independently associated with vedolizumab outcomes at multivariable analysis. A panel of soluble markers, including IL17A, TNF, CXCL1, CCL19 for CD and G-CSF and IL7 for UC, associated with vedolizumab-induced Week 54 clinical remission. Conclusions The results of this exploratory study uncovered a panel of circulating and mucosal immunological variables associated with response to treatment with vedolizumab.

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

Pediatrician (St Petersburg) ◽

10.17816/ped6391-97 ◽

2015 ◽

Vol 6 (3) ◽

pp. 91-97 ◽

Cited By ~ 1

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.

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