Biomarkers for Optimization and Personalization of Anti-TNFs in Pediatric Inflammatory Bowel Disease.
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ABSTRACT:
SUBMITTER: Salvador-Martin S
PROVIDER: S-EPMC8617733 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tumor necrosis factor (TNF) alpha is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathway.
| S-EPMC4783957 | biostudies-literature
Project description:OBJECTIVES:In patients with inflammatory bowel disease (IBD) using biological therapy, non-adherence leads to anti-drug antibody formation and reduced effectiveness. Little is known about the optimal level of adherence in IBD patients on biologic therapy. We aimed to identify the association between adherence and disease flare and determine an optimal level of adherence. METHODS:We analyzed claims data for IBD patients prescribed adalimumab (ADA) and certolizumab (CZP) from the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. Adherence was calculated using the medication possession ratio (MPR) from initiation until flare occurrence. A disease flare was defined as any hospitalization or new steroid prescription>90-days after drug initiation. The optimal MPR was determined using log-rank testing. The association between the optimal MPR and flare was assessed using multivariable Cox-Proportional hazards ratio. RESULTS:There were 6,048 patients who were prescribed ADA (n=5,325) or CZP (n=723) for IBD. The average age was 41 years (±15) and 54% were female. The optimal MPR identified was 0.86 for ADA and 0.87 for CZP; 24% of the patients were below this level. Adjusting for age, gender, and concomitant medications at initiation, patients who were adherent above these levels had a 25% lower risk of flare for ADA (HR: 0.75, 95%CI: 0.67-0.83, P<0.01) and 41% lower risk for CZP (HR: 0.59, 95%CI: 0.46-0.76, P<0.01). CONCLUSIONS:Patients who delay refills >2 days on average every 2 weeks of their subcutaneous biologics have significantly increased risk of flare. Further studies to improve adherence among those patients who consistently delay medication use are necessary.
| S-EPMC5931803 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is characterized as chronic inflammation in the gastrointestinal tract, which includes two main subtypes, Crohn's disease and ulcerative colitis. Endoscopy combined with biopsy is the most effective way to establish IBD diagnosis and disease management. Imaging techniques have also been developed to monitor IBD. Although effective, the methods are expensive and invasive, which leads to pain and discomfort. Alternative noninvasive biomarkers are being explored as tools for IBD prognosis and disease management. This review focuses on novel biomarkers that have emerged in recent years. These serological biomarkers and microRNAs could potentially be used for disease management in IBD, thereby decreasing patient discomfort and morbidity.
| S-EPMC10321231 | biostudies-literature
Project description:Purpose of the reviewThis review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD).Recent findingsSeveral real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.
| S-EPMC10865142 | biostudies-literature
Project description:BackgroundA growing body of evidence underscores the beneficial impact of therapeutic drug monitoring (TDM) on the efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD).ObjectivesWe surveyed clinician attitudes, perceptions and barriers related to TDM in IBD in the Middle East.DesignA 15-question survey was distributed through national gastroenterological societies in five Middle Eastern countries (UAE, Saudi Arabia, Kuwait, Lebanon and Egypt).MethodsData on clinician characteristics, demographics, utilization patterns and obstacles related to the adoption of TDM with anti-TNFs were gathered. Logistic regression analysis was used to predict factors influencing the utilization of TDM.ResultsAmong 211 respondents (82% male), 82% were consultants, 8% were physicians with an interest in gastroenterology (GI), and 6% were GI trainees. Of these, 152 met inclusion criteria, treating >5 IBD patients per month and ⩾1 with an anti-TNF per month. TDM was used in clinical practice by 78% (95% CI: 71-85) of respondents. TDM was utilized following the loss of response (LOR) in 93%, for primary non-response (PNR) in 40% and before restarting anti-TNF therapy after a drug holiday in 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to results (71%) and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%) or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday, and 54% would use TDM proactively.ConclusionMost gastroenterologists use TDM for LOR, with cost, time lag and insurance reimbursement being significant barriers. Addressing these barriers would increase the judicious use of reactive and proactive TDM to optimize anti-TNF therapy in IBD.
| S-EPMC10894550 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease.
| S-EPMC4055235 | biostudies-literature
Project description:Shared decision making (SDM) is central to patient-centered medicine and has the potential to improve outcomes for pediatric patients with inflammatory bowel diseases. We surveyed specialists about their use of SDM in the decision to start a tumor necrosis factor-α inhibitor in pediatric patients. Results were compared between those who reported using SDM and those who did not. Of 209 respondents, 157 (75%) reported using SDM. Physician/practice characteristics were similar between users and nonusers. There were no statistically significant differences between groups in the components deemed important to the decision-making process nor the number of barriers or facilitators to SDM. Exploratory analyses suggested that physicians using SDM were more accepting of adolescent involvement in the decision-making process. Our results question the effectiveness of using reported barriers and facilitators to guide interventions to improve use of SDM, and suggest further work is needed to understand the adolescent role in decision making.
| S-EPMC7055652 | biostudies-literature
Project description:UnlabelledIn adult inflammatory bowel disease (IBD) patients, there is a strong discrepancy between symptoms and biomarkers of inflammation. Data on pediatric IBD patients are conflicting. Therefore, we aimed to investigate the relationship between clinical symptoms and biomarkers of inflammation in pediatric IBD. Patients aged <18 years with previously diagnosed Crohn's disease (CD) or ulcerative colitis (UC) were included. Clinical disease activity was determined using the abbreviated Pediatric CD Activity Index (aPCDAI) or Pediatric UC Activity Index (PUCAI). Biochemical disease activity was assessed using fecal calprotectin (FC) and C-reactive protein (CRP). In total, 127 patients (62 male; median age 14.9 years) were included (82 CD, 45 UC). FC correlated weakly with total aPCDAI score (r s = 0.32; 95 % CI 0.12-0.51; p = 0.003) and total PUCAI score (r s = 0.36; 95 % CI 0.07-0.62; p = 0.015). Only aPCDAI components abdominal examination and perirectal disease and PUCAI component activity level had a significant correlation with levels of FC. CRP correlated weakly with total aPCDAI score (r s = 0.28; 95 % CI 0.05-0.46; p = 0.012) and aPCDAI components abdominal examination and activity level. No significant correlation was observed between CRP and total PUCAI score (r s = 0.01; 95 % CI -0.34-0.29; p = 0.961) or individual PUCAI components.ConclusionThere is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.What is known• A substantial proportion of asymptomatic pediatric inflammatory bowel disease (IBD) patients have elevated biomarkers of inflammation. • There is a strong discrepancy between symptoms and biomarkers of inflammation in adults with IBD. What is New: • Clinical symptoms are only weakly associated with levels of fecal calprotectin and serum C-reactive protein in children and adolescents with previously diagnosed IBD. • Similarly to adult IBD patients, there is a strong discrepancy between clinical symptoms and biomarkers of inflammation in children with IBD.
| S-EPMC5031739 | biostudies-literature
Project description:Background: In pediatric inflammatory bowel disease (IBD) up to 30% of patients do not respond to anti-TNF therapy. The aim was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: The study population included 29 responders and 9 non-responders to anti-TNF therapy patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Whole gene expression profiles from total RNA isolated from whole-blood samples of 6 responders and 6 non-responders taken before biologic administration and after 2 weeks were analyzed by RNA next-generation sequencing. The expression of 6 selected genes was measured for validation in all of 38 patients recruited using qPCR; Results: Differentially expressed genes in non-responders versus responders to anti-TNF treatment were identified, 32 prior treatment initiation and 44 after 2 weeks (Log2FC (Fold change)>0.6 o <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B and GBP1 were overexpressed in non-responders after 2 weeks of anti-TNF treatment (Log2FC 1.05, 1.21 and 1.08, respectively, p value <0.05,); Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
2021-01-14 | GSE159034 | GEO
Project description:Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids.Aims: To review the available data on serological biomarkers for IBD.Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD.Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management.Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
| S-EPMC7188783 | biostudies-literature