scholarly journals RAID Prediction: Pilot Study of Fecal Microbial Signature With Capacity to Predict Response to Anti-TNF Treatment

2021 ◽  
Vol 27 (Supplement_2) ◽  
pp. S63-S66 ◽  
Author(s):  
David Busquets ◽  
Lia Oliver ◽  
Joan Amoedo ◽  
Sara Ramió-Pujol ◽  
Marta Malagón ◽  
...  
Keyword(s):  
Predictive Value ◽  
High Capacity ◽  
Predictive Ability ◽  
High Sensitivity ◽  
Biologic Treatment ◽  
Life Saving ◽  
Variable Duration ◽  
Inflammatory Bowel ◽  
Stool Samples

Abstract Background and Aims Crohn’s disease and ulcerative colitis evolve with alternate outbreaks and remissions of variable duration in both cases. Despite the advances, about 10-30% of patients do not respond to the treatment after the induction period. Besides, between 20% to 50% further patients need an optimization of the dose to respond the treatment. Recent studies have pointed gut microbiota can play a role in the anti-TNF treatment response. This study aimed to define a bacterial signature that could be used to predict the response of patients to anti-TNF treatment. Methods There were obtained 38 stool samples from 38 IBD patients before starting anti-TNF treatments: Adalimumab, Golimumab or Infliximab. Patients were differentiated in 2 groups: responders and non-responders to biological treatment. From each sample, DNA was purified and used in a qPCR for the quantification of the 8 microbial markers. Results In this proof of concept, the predictive ability to identify anti-TNF treatment responders was analyzed. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and non- responders. The algorithm proved high sensitivity and specificity reporting values of 93.33% and 100% respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment. Conclusions A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effectiveness of an anti-TNF treatment, leading to a personalized therapy, improving the patients’ quality of life, saving costs and gaining time in patient improvement.

scholarly journals P674 Definition of a microbial signature as a predictor of anti-TNFα treatment response

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S595-S595
Author(s):  
L Oliver ◽  
D Busquets ◽  
J Amoedo ◽  
S Ramió-Pujol ◽  
M Malagón ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Treatment Response ◽  
Sensitivity And Specificity ◽  
Predictive Value ◽  
Bacterial Load ◽  
High Sensitivity ◽  
Response To Treatment ◽  
Biologic Treatment ◽  
Faecal Calprotectin

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) evolve with alternate outbreaks and remissions of variable duration. Tumour necrosis factor α antagonists (anti-TNFα) have enhanced the treatment of patients with inflammatory bowel disease (IBD), improving the patient’s quality of life by reducing the number of surgeries and hospitalizations. Despite these advances, about 10–30% of patients do not respond to the treatment after the induction period. Recent studies have pointed, on one hand, gut microbiota can play a role in the anti-TNFα treatment response as gram-positive bacteria can modulate the response of NOD proteins and, on the other hand, gram-negative bacteria can stimulate TLR4 receptors causing activation of NFkß. This study aimed to define a microbial signature that could be used to predict the response of patients with CD and UC to anti-TNFα treatment. Methods This observational study consisted of obtaining a stool sample from 38 IBD patients before starting an anti-TNFα treatment. Patients were recruited at Hospital Universitari Dr. Josep Trueta (Girona) and Hospital Universitari de Bellvitge (l’Hospitalet de Llobregat). During the one-year follow-up period, disease activity levels, faecal calprotectin evolution, and anti-TNFα antibody levels were analysed to assess response to treatment, differentiating 2 groups: responders and non-responders. From each sample, DNA was purified and used in a qPCR for the quantification of the following markers: F. prausnitzii (Fpra) and its phylogroups (PHG-I and PHG-II), E. coli (Eco), A. muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac), M. smithii (Msm), and the total bacterial load (Eub). Results In this proof of concept, the predictive ability to identify anti-TNFα treatment responders was analysed. Individually, none of biomarkers demonstrated the ability to differentiate between groups with high sensitivity and specificity. However, an algorithm consisting of the combination of 5 microbial markers (Msm, Fpra, PHGII, Rum, and Eub) showed a high capacity to discriminate between responders and non-responders. The algorithm proved high sensitivity and specificity reporting values ​​of 93.33% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment. Conclusion A specific microbial signature could beneficiate patients with IBD by predicting the therapeutic effectiveness of an anti-TNFα treatment, which could lead to a personalized therapy, improving the patients’ quality of life, saving costs, and gaining time in patient recovery.A larger prospective study will be needed to validate these results.

scholarly journals Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maria Sakalaki ◽  
Per-Olof Hansson ◽  
Annika Rosengren ◽  
Erik Thunström ◽  
Aldina Pivodic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
General Population ◽  
Predictive Value ◽  
Population Sample ◽  
Predictive Ability ◽  
High Sensitivity ◽  
Hs Crp

Abstract Background Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied. Purpose To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age. Method “The Study of Men Born in 1943” is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups. Results Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model’s discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up. Conclusion In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population. Trial registration: The study is registered at Clinical Trials.gov Identifier number: NCT03138122

scholarly journals P634 Predictors of response and course in patients with inflammatory bowel disease treated with biological therapy: The Danish IBD-Biobank project

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S526-S527
Author(s):  
M Zhao ◽  
F Bendtsen ◽  
A M Petersen ◽  
L Larsen ◽  
T Jess ◽  
...  
Keyword(s):  
Protein Expression ◽  
Treatment Response ◽  
Prospective Cohort ◽  
Biological Therapy ◽  
First Line ◽  
Intestinal Tissue ◽  
Biologic Treatment ◽  
Inflammatory Bowel ◽  
Stool Samples ◽  
One Year

Abstract Background Biologic treatment has revolutionised the treatment of inflammatory bowel diseases (IBD) and has been shown to reduce surgery and hospitalisation rates in patients with severe disease. Up to one-third of patients do not respond to first-line biologic drugs and another third loses response with time. This highlights an unmet need for optimising the use of biologics and for predicting treatment response to biologics. We present the initial recruitment stages and experimental pipeline for The Danish IBD Biobank which aims to identify predictive biomarkers of response and disease course in patients with IBD who receive biologics. Methods The Danish IBD Biobank constitutes a multicenter prospective cohort study aiming to include 840 biological-naïve adult patients with IBD who initiate biologic therapy in a three-year period from May 2019 and onwards. Primary outcomes are the occurrence of primary non-response (PNR) evaluated at week 14–16 and loss of response (LOR) evaluated during the entire follow-up. Patients will be followed with clinical data for at least one year or until May 2022 and sampled for blood, stool and intestinal tissue during the first year of treatment. Blood and stool samples are collected at each visit for biologic treatment and upon change in drug type, dosing or discontinuation. Intestinal tissue is sampled whenever an endoscopy is performed and after one year of treatment (Figure 1). Results As of 15 November 2019, 132 patients have been recruited to the cohort. Biologic treatment was indicated due to acute severe ulcerative colitis (UC) or chronic active UC in 13% and 43% of patients, respectively, while 38% and 6% received treatment for luminal Crohn’s disease (CD) and perianal CD. In accordance with national guidelines issued by the Danish Medicines Council, infliximab was the most commonly used first-line drug (98%), followed by vedolizumab (2%) and adalimumab (0.8%). Among 68 patients who have completed induction therapy so far, PNR occurred in 35% (62% UC, 38% CD). Among those with PNR, 50% switched class, 21% discontinued treatment and 29% underwent surgery. Blood and stool samples and intestinal biopsies are stored in a biobank awaiting characterisation of RNA and protein expression using multiplex immunoassay, 16S and Illumina sequencing, and characterisation of mucosal gene and protein expression (Figure 2). Conclusion The Danish IBD Biobank project aiming to identify predictive transcriptomic, microbial and proteomic biomarkers associated with treatment response and outcomes to biological therapy in a prospective cohort of biological-naïve IBD patients has been successfully launched. Funding This study is funded by an unrestricted grant from Takeda A/S and public fund hosted by Hvidovre Hospital.

Psychosocial Aspects of Quality of Life for Inflammatory Bowel Disease

2006 ◽  
Author(s):  
Carmen E. Curtis ◽  
Gary W. Harper ◽  
Leonard A. Jason ◽  
Brigida Hernandez
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Psychosocial Aspects ◽  
Inflammatory Bowel

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.

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