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

2020 ◽  
Vol 9 (3) ◽  
pp. 800 ◽  
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.

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

2020 ◽  
Vol 14 (9) ◽  
pp. 1190-1201 ◽  
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.

Does Infliximab Short Infusion have a Beneficial Impact on the Quality of Life in Patients with Inflammatory Bowel Diseases? A Single Centre Prospective Evaluation

2015 ◽  
Vol 24 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Mariabeatrice Principi ◽  
Giuseppe Losurdo ◽  
Rosa Federica La Fortezza ◽  
Pasquale Lopolito ◽  
Rosa Lovero ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Diseases ◽  
Adverse Reactions ◽  
Severe Disease ◽  
Sexual Life ◽  
Necrosis Factor Alpha ◽  
Short Infusion ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background & Aims: Infliximab (IFX) is an anti-tumor necrosis factor alpha agent used in inflammatory bowel diseases (IBD) therapy. Usually, it is administered over a 2-hour intravenous infusion. However, shortening the infusion duration to 1 hour has proved to be feasible and safe. In the present study we evaluated whether shortening the IFX infusion could affect the patients' quality of life (QoL) compared to the standard protocol.Methods: Subjects affected by IBD receiving IFX were prospectively recruited. The main criterion to shorten the infusion was the absence of IFX-related adverse reactions during the previous three 2-h infusions. For each patient, demographic, clinical and anthropometric data were collected. A questionnaire investigating their overall/job/social/sexual QoL was administered. Ordinal regression was performed with odds ratios (OR) for significant independent variables.Results: Eighty-one patients were included (46 with ulcerative colitis - UC, 35 with Crohn's disease - CD). Sixteen received the 2-h infusion due to previous adverse reactions, and the remaining 65 underwent the 1-h schedule. Shortening the infusion to 1 hour determined a better QoL (OR=0.626). However, the QoL was negatively influenced by age (OR=1.023), female sex (OR=2.04) and severe disease activity (OR=7.242). One-hour IFX infusion induced a better outcome on work (OR=0.588) and social (OR=0.643) QoL. Long-standing disease was correlated with a slightly better sexual QoL (OR=0.93). Conversely, older age (OR=1.046), severe clinical score (OR=15.579), use of other immunomodulators (OR=3.693) and perianal CD (OR=3.265) were related to an unsatisfactory sexual life. The total number of infusions (OR=0.891), proctitis (OR=0.062) or pancolitis (OR=0.1) minimized the perception of infusion-related side effects.Conclusion: The 1-h short infusion improves overall, social and job QoL, so that, when indicated, it should be recommended.

Phase I, II and III Trials in Inflammatory Bowel Diseases: A Practical Guide for the Non-specialist

2020 ◽  
Vol 14 (5) ◽  
pp. 710-718 ◽  
Author(s):  
Ferdinando D’Amico ◽  
Cedric Baumann ◽  
Hélène Rousseau ◽  
Silvio Danese ◽  
Laurent Peyrin-Biroulet
Keyword(s):  
Clinical Trial ◽  
Data Analysis ◽  
Inflammatory Bowel Diseases ◽  
Control Group ◽  
Patient Stratification ◽  
Clinical Phase ◽  
New Drug ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Design Type

Abstract In the last few decades several new molecules have been developed in the field of inflammatory bowel diseases. However, the process that leads to the approval and use of a new drug is very long, expensive and complex, consisting of various phases. There is a pre-clinical phase that is performed on animals and a clinical phase that is directed to humans. Each research phase aims to evaluate different aspects of the drug and involves a specific target group of subjects. In addition, many aspects must be considered in the evaluation of a clinical trial: randomization, presence of a control group, blind design, type of data analysis performed, and patient stratification. The objective of this review is to provide an overview of the clinical trial phases of a new drug in order to better understand and interpret their results.

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.

scholarly journals Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases

2017 ◽  
Vol 21 (5) ◽  
pp. 603-610.e3 ◽  
Author(s):  
Ashwin N. Ananthakrishnan ◽  
Chengwei Luo ◽  
Vijay Yajnik ◽  
Hamed Khalili ◽  
John J. Garber ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Gut Microbiome ◽  
Biologic Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals The Prevalence of Adherent-Invasive Escherichia coli and Its Association With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Razie Kamali Dolatabadi ◽  
Awat Feizi ◽  
Mehrdad Halaji ◽  
Hossein Fazeli ◽  
Peyman Adibi
Keyword(s):  
Escherichia Coli ◽  
Systematic Review ◽  
Inflammatory Bowel Diseases ◽  
Meta Analysis ◽  
Control Group ◽  
Pooled Prevalence ◽  
Bowel Diseases ◽  
Phylogenetic Grouping ◽  
Inflammatory Bowel ◽  
And Control

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are known as chronic gastrointestinal inflammatory disorders. The present systematic review and meta analysis was conducted to estimate the prevalence of adherent-invasive Escherichia coli (AIEC) isolates and their phylogenetic grouping among IBD patients compared with the controls. A systematic literature search was conducted among published papers by international authors until April 30, 2020 in Web of Science, Scopus, EMBASE, and PubMed databases. The pooled prevalence of AIEC isolates and their phylogenetic grouping among IBD patients as well as in controls was estimated using fixed or random effects models. Furthermore, for estimating the association of colonization by AIEC with IBD, odds ratio along with 95% confidence interval was reported. A total of 205 articles retrieved by the initial search of databases, 13 case–control studies met the eligibility criteria for inclusion in the meta analysis. There were 465 IBD cases (348 CD and 117 UC) and 307 controls. The pooled prevalence of AIEC isolates were 28% (95% CI: 18–39%), 29% (95% CI: 20–40%), 13% (95% CI: 1–30%), and 9% (95% CI: 3–19%), respectively among IBD, CD, UC, and control group, respectively. Our results revealed that the most frequent AIEC phylogroup in the IBD, CD, and control groups was B2. Fixed-effects meta analysis showed that colonization of AIEC is significantly associated with IBD (OR: 2.93; 95% CI: 1.90–4.52; P &lt; 0.001) and CD (OR: 3.07; 95% CI: 1.99–4.74; P &lt; 0.001), but not with UC (OR: 2.29; 95% CI: 0.81–6.51; P = 0.11). In summary, this meta analysis revealed that colonization by AIEC is more frequent in IBD and is associated with IBD (CD and UC). Our results suggested that the affects of IBD in patients colonized with the AIEC pathovar is not random, it is in fact a specific disease-related pathovar.

scholarly journals Vedolizumab: Potential Mechanisms of Action for Reducing Pathological Inflammation in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Matthew Luzentales-Simpson ◽  
Yvonne C. F. Pang ◽  
Ada Zhang ◽  
James A. Sousa ◽  
Laura M. Sly
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Bowel Diseases ◽  
Necrosis Factor Alpha ◽  
Cell Recruitment ◽  
Inflammatory Monocytes ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Cytokine Tumor Necrosis Factor ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis (UC), and Crohn’s disease (CD), are a group of disorders characterized by chronic, relapsing, and remitting, or progressive inflammation along the gastrointestinal tract. IBD is accompanied by massive infiltration of circulating leukocytes into the intestinal mucosa. Leukocytes such as neutrophils, monocytes, and T-cells are recruited to the affected site, exacerbating inflammation and causing tissue damage. Current treatments used to block inflammation in IBD include aminosalicylates, corticosteroids, immunosuppressants, and biologics. The first successful biologic, which revolutionized IBD treatment, targeted the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα). Infliximab, adalimumab, and other anti-TNF antibodies neutralize TNFα, preventing interactions with its receptors and reducing the inflammatory response. However, up to 40% of people with IBD become unresponsive to anti-TNFα therapy. Thus, more recent biologics have been designed to block leukocyte trafficking to the inflamed intestine by targeting integrins and adhesins. For example, natalizumab targets the α4 chain of integrin heterodimers, α4β1 and α4β7, on leukocytes. However, binding of α4β1 is associated with increased risk for developing progressive multifocal leukoencephalopathy, an often-fatal disease, and thus, it is not used to treat IBD. To target leukocyte infiltration without this life-threatening complication, vedolizumab was developed. Vedolizumab specifically targets the α4β7 integrin and was approved to treat IBD based on the presumption that it would block T-cell recruitment to the intestine. Though vedolizumab is an effective treatment for IBD, some studies suggest that it may not block T-cell recruitment to the intestine and its mechanism(s) of action remain unclear. Vedolizumab may reduce inflammation by blocking recruitment of T-cells, or pro-inflammatory monocytes and dendritic cells to the intestine, and/or vedolizumab may lead to changes in the programming of innate and acquired immune cells dampening down inflammation.

Sign in / Sign up

Export Citation Format

Share Document