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 ◽  
...  

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.

2020 ◽  
Vol 21 (8) ◽  
pp. 2940
Author(s):  
Antonelly Cassio Alves de Carvalho ◽  
Gabriela Achete de Souza ◽  
Samylla Vaz de Marqui ◽  
Élen Landgraf Guiguer ◽  
Adriano Cressoni Araújo ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.


2019 ◽  
Vol 20 (19) ◽  
pp. 4851 ◽  
Author(s):  
Ledyane Taynara Marton ◽  
Ricardo de Alvares Goulart ◽  
Antonelly Cassio Alves de Carvalho ◽  
Sandra Maria Barbalho

Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn’s disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes and, for these reasons, we aimed to review the effects of these acids on UC and CD. Databases such as PUMED and EMBASE were searched, and the final selection included fifteen studies that fulfilled the inclusion criteria. The results showed that ω3 fatty acids reduce intestinal inflammation, induce and maintain clinical remission in UC patients, and are related with the reduction of proinflammatory cytokines, decrease disease activity and increase the quality of life of CD patients. Furthermore, the consumption of these fatty acids may be related to a reduced risk of developing IBD. Many studies have shown the beneficial effects of ω3 as adjunctive in the treatment or prevention of UC or CD. Nevertheless, most were performed with a small number of patients and there are many variations in the mode of consumption, the type of food or the type of formulation used. All these factors substantially interfere with the results and do not allow reliable comparisons.


2020 ◽  
Vol 92 (2) ◽  
pp. 67-73
Author(s):  
M. V. Shapina ◽  
B. A. Nanaeva

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.


2020 ◽  
Vol 9 (3) ◽  
pp. 800 ◽  
Author(s):  
Gian Caviglia ◽  
Chiara Rosso ◽  
Francesco Stalla ◽  
Martina Rizzo ◽  
Alessandro Massano ◽  
...  

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.


2020 ◽  
Vol 14 (9) ◽  
pp. 1190-1201 ◽  
Author(s):  
Marina Coletta ◽  
Moira Paroni ◽  
Maria Francesca Alvisi ◽  
Matilde De Luca ◽  
Eliana Rulli ◽  
...  

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.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S259-S260
Author(s):  
G Babayeva-Sadigova ◽  
Z Babayev ◽  
G Asadova ◽  
U Mahmudov ◽  
F Quliyev ◽  
...  

Abstract Background The prevalence of opportunistic infections in individuals with inflammatory bowel disease (IBD) remains relevant. Viral infections are a common cause of systemic inflammation of the digestive tract. Clinically expressed herpes and parvovirus infections are a serious problem, especially for people with prolonged immunosuppression. The aim of the study was t o assess the incidence of certain herpes and parvovirus infections in patients with IBD. Methods In total, 189 patients with IBD, 102 with ulcerative colitis and 87 with Crohn’s disease were examined. Of the number of patients: 98 women, 91man. The age of patients is from 16 to 63 years (mean age 41.4 ± 4.8). In addition to a standard examination, disease activity was assessed by indicators of highly sensitive C-reactive protein, homocysteine, vitamin D in blood serum, albumin in urine, calprotectin and lactoferrin in faeces. All patients underwent serological blood tests by ELISA for specific antibodies to herpes viruses and IgG/IgM antibodies to parvovirus B19, determination of DNA to herpes simplex viruses of types 1-2,6(HSV1-2?HSV6), Epstein–Barr (EBV}, cytomegalovirus (CMV), herpes zoster (HZV) by PCR in blood and mucosal biopsy, and also avidity. Results Among patients with IBD, active infections (herpes and parvoviruses) in the blood occurred in 81 patients (42.8%); of them, 39 patients (20.6%) were diagnosed with monoherpesvirus infections, in 16 patients parvovirus (8.4%), and in 26 (13.8%) cases, active mixed viral infections were detected. In 79 cases (41.7%) of PCR biopsy material was positive for isolated infection: 36 cases (19%) of CMV, 21 cases (11.1%) of EBV, 22 cases (11.6%) of HSV6. Tissue viral infection was found in 34 patients (17.9%). Clinical endoscopic and laboratory indicators of activity in IBD were significantly higher in patients with active viral infections (p ˂ 0.05), which indicates the negative effect of chronic active herpes and parvovirus infections on the course of inflammatory bowel diseases. However, significant differences between patients with ulcerative colitis and Crohn’s disease were not detected. Conclusion The frequency of occurrence of herpes and parvovirus lesions in patients with IBD in the blood is more than 42.8%, isolated infection in the tissue in 41.7%, and mixed infection in 17.9% of the number of patients. The clinical endoscopic picture, as well as laboratory data indicate a more severe course of diseases in the presence of these infections.


2020 ◽  
Vol 14 (11) ◽  
pp. 1512-1523
Author(s):  
Catherine Le Berre ◽  
Mathurin Flamant ◽  
Guillaume Bouguen ◽  
Laurent Siproudhis ◽  
Marie Dewitte ◽  
...  

Abstract Background and Aims Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time. Methods From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits. Results A total of 447 patients [71% Crohn’s disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p &lt;0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach’s α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time. Conclusions This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC.


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