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.

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.

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 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.

IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases

2020 ◽  
Author(s):  
Yonghong Yang ◽  
Cui Zhang ◽  
Dehuai Jing ◽  
Heng He ◽  
Xiaoyu Li ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Activity ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Orphan Receptor ◽  
Peripheral Blood Mononuclear ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory disorders. As is well known, interferon regulatory factor (IRF) 5 is closely associated with the pathogenesis of various inflammatory diseases. But the exact role of IRF5 in IBD remains unclear. Methods In this study, we detected IRF5 expression in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction. Peripheral blood CD4+ T cells were stimulated with inflammatory cytokines and transfected by lentivirus. Results In active IBD patients, the expression of IRF5 in PBMCs and inflamed colonic tissues was obviously increased and significantly associated with disease activity. Ectopic overexpression of IRF5 could promote the differentiation of IBD CD4+ T cells into Th1 and Th17 cells by regulating T-bet and RAR related orphan receptor C, whereas knockdown of IRF5 had the opposite effects. Tumor necrosis factor (TNF)-α upregulated expression of IRF5 in CD4+ T cells, but anti-TNF treatment with infliximab could markedly reduce IRF5 expression in CD4+ T cells and intestinal mucosa of CD patients. Conclusion Our study reveals a novel mechanism that IRF5 levels are correlated with disease activity in IBD and might function as a possible marker for the management of IBD via regulating Th1 and Th17 immune responses and cytokine production.

scholarly journals P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S342-S342
Author(s):  
S Mazza ◽  
A Fascì ◽  
V Casini ◽  
C Ricci ◽  
F Munari ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inflammatory Bowel Diseases ◽  
Clinical Remission ◽  
Comparable Efficacy ◽  
Potential Cost ◽  
Safety And Efficacy ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Double Switch

Abstract Background Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking. Methods This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13. Results Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13-&gt;SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes. Conclusion The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.

scholarly journals Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases

2012 ◽  
Vol 18 (12) ◽  
pp. 2334-2341 ◽  
Author(s):  
Alan R. Harris ◽  
Dorottya Nagy-Szakal ◽  
Natalia Pedersen ◽  
Antone Opekun ◽  
Jiri Bronsky ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Diseases ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocyte ◽  
Genome Wide ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Blood Leukocyte

scholarly journals P266 Atopic diseases are associated with the development of inflammatory bowel diseases: A nationwide population-based study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S282-S283
Author(s):  
S W Hong ◽  
H Soh ◽  
H J Lee ◽  
K Han ◽  
S Park ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Multivariable Analysis ◽  
Atopic Disease ◽  
Population Based ◽  
Atopic Diseases ◽  
Population Based Study ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background The association between atopic diseases and inflammatory bowel diseases (IBD) still remains unclear. We conducted a nationwide population-based study to investigate the effect of atopic diseases on the development of IBD. Methods A total of 9,950,548 subjects who received medical check-up between 2009 and 2012 were included and followed up until 2017. The presence of any atopic disease including atopic dermatitis (AD), allergic rhinitis (AR), and asthma were evaluated. Patients who developed IBD including Crohn’s disease (CD) and ulcerative colitis (UC) were identified using the claims data from National Health Insurance. Results During a mean follow up of 7.3 years, 1,426 (0.014%) subjects developed CD and 5,916 (0.059%) subjects developed UC. The incidences of CD (per 100,000 person-years) were 4.088, 2.255, and 2.344 in patients with AD, AR, and asthma,, respectively. The incidences of UC were 11.926, 9.857, and 9.377 in patients with AD, AR, and asthma, respectively. Multivariable analysis revealed that the adjusted hazard ratios (aHR) for incident CD in patients with AD, AR, and asthma were 2.21, 1.33, and 1.59 (95% confidence interval (CI) 1.251–3.896, 1.152–1.532, and 1.186–2.123, respectively) compared with controls. The risk for incident UC in patients in AD, AR, and asthma were 1.51, 1.32, and 1.28 (95% CI 1.081–2.101, 1.235–1.416, and 1.110–1.484, respectively) compared with controls. Moreover, increase in the number of atopic diseases gradually increased the risk for CD and UC; CD showed aHR of 1.36 and 1.65 (95% CI 1.180–1.571 and 1.143–2.370), and UC showed aHR of 1.30 and 1.49 (95% CI 1.216–1.398 and 1.247-1.170) in one, and two or more atopic diseases, respectively. Conclusion Patients with any atopic diseases showed an increased risk for IBD, while an increase in the number of atopic diseases gradually increased the risk for IBD.

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