Biologic Therapies Targeting Eosinophilic Gastrointestinal Diseases.
Ontology highlight
ABSTRACT:
SUBMITTER: Oshima T
PROVIDER: S-EPMC10749800 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Biologic Therapies Targeting Eosinophilic Gastrointestinal Diseases.
Internal medicine (Tokyo, Japan) 20230421 23
Similar Datasets
Project description:The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.
| S-EPMC6035775 | biostudies-literature
Project description:Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.
| S-EPMC9356173 | biostudies-literature
Project description:Eosinophilic gastrointestinal diseases are a constellation of conditions categorized by the location of eosinophilic infiltration in the gastrointestinal tract. Symptoms vary based on location of eosinophils and age of the patient. There are no approved medications at the current time with individuals using off-label steroids or dietary therapy. Translational research has identified potential pathways to target in the treatment of eosinophilic esophagitis (EoE), gastritis (EoG), and enteritis (EoN), including type 2 pathways, mast cells, and eosinophils. Preliminary studies found cendakimab (anti-interleukin [IL]-13) and dupilumab (anti-IL-4 receptor alpha) to have an effect on eosinophil count and symptoms with dupilumab recently approved. In addition, mepolizumab (anti-IL-5), reslizumab (anti-IL-5), and lirentelimab (anti-Siglec 8) were found to have reduction in eosinophils without reduction of symptoms. For EoG and EoN, both benralizumab (anti-IL-5 receptor) and lirentelimab were found to have histologic and symptom improvement. There are no agents studied for eosinophilic colitis. Results of ongoing phase 3 trials in EoE and EoG/EoN are also anticipated.
| S-EPMC10191215 | biostudies-literature
Project description:Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.
| S-EPMC5506279 | biostudies-literature
Project description:Approximately 20-40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is associated with inferior outcomes in patients with IBD, with lower rates of achieving remission, poor quality of life, and higher burden of unplanned healthcare utilization. Multiple cohort studies in patients with immune-mediated inflammatory diseases, including IBD, treated with biologic agents like tumor necrosis factor-α antagonists have suggested that obesity is associated with inferior response to biologic therapy. This may be related to the negative impact of obesity on the pharmacokinetics of biologic agents. Pharmacokinetic studies of multiple biologic agents have demonstrated that high body weight is associated with more rapid clearance and a higher volume of distribution of biologic agents, which leads to low trough concentrations. Randomized trials in patients with psoriasis and psoriatic arthritis treated with biologic agents suggest that diet- or lifestyle-induced weight loss is associated with improved response to therapy. This provides an opportunity to explore intentional weight loss as adjunctive therapy in obese patients with IBD. However, diet and lifestyle interventions for weight loss are hard to implement in patients with IBD; hence, long-term therapy with weight-loss agents (such as with phentermine-topiramate, naltrexone-bupropion) is attractive as adjunctive therapy in obese patients with IBD.
| S-EPMC8994033 | biostudies-literature
Project description:Biologic therapies have revolutionized the treatment of severe allergic diseases, including asthma, atopic dermatitis (AD), chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic gastrointestinal diseases (EGIDs), and allergic rhinitis (AR). These molecularly targeted agents provide significant benefits for patients unresponsive to conventional treatments by addressing underlying immune mechanisms, particularly type 2 inflammation driven by cytokines such as IL-4, IL-5, and IL-13. Recent advancements include biologics targeting alarmins like thymic stromal lymphopoietin (TSLP) and IL-33, which may address both type 2 and non-type 2 inflammation, broadening their therapeutic scope. Despite their effectiveness, biologics remain expensive, posing socioeconomic challenges, and there are concerns regarding long-term safety and inter-individual variability in responses. Promising innovations such as bispecific antibodies and ultra-long-acting agents are under investigation, alongside digital health tools like remote biomarker monitoring and AI-driven decision support systems, which aim to enhance personalized care. However, disparities in access, particularly for underserved populations, underscore the need for policy reforms and affordable biosimilars. This review synthesizes recent findings and emerging trends, highlighting the evolving role of biologics in transforming allergic disease management and offering insights into future research directions.
| S-EPMC11856668 | biostudies-literature
Project description:The complement cascade is part of the innate immune system whose actions protect hosts from pathogens. Recent research shows complement involvement in a wide spectrum of renal disease pathogenesis including antibody-related glomerulopathies and non-antibody-mediated kidney diseases, such as C3 glomerular disease, atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. A pivotal role in renal pathogenesis makes targeting complement activation an attractive therapeutic strategy. Over the last decade, a growing number of anti-complement agents have been developed; some are approved for clinical use and many others are in the pipeline. Herein, we review the pathways of complement activation and regulation, illustrate its role instigating or amplifying glomerular injury, and discuss the most promising novel complement-targeting therapies.
| S-EPMC6940904 | biostudies-literature
Project description:Gastrointestinal basidiobolomycosis (GIB) is unusual, rare, and emerging fungal infection. It is caused by Basidiobolus ranarum. Unlike other fungal infections, B ranarum affects immunocompetent individuals with potentially grave sequelae if unrecognized. GIB is difficult to be diagnosed due to unspecific clinical presentation. Diagnosis of basidiobolomycosis requires culture of B ranarum from tissue. Optimal management of GIB includes antifungal therapy alongside if necessary early surgery.
| S-EPMC10191557 | biostudies-literature
Project description:Current therapies for eosinophilic disorders are limited. Most treatment approaches remain empirical, are not supported by data from controlled clinical trials, involve the off-label use of agents developed for treatment of other diseases, and tend to rely heavily on the use of glucocorticoids and other agents with significant toxicity. Great progress has been made in the discovery, preclinical development, and clinical testing of a variety of biologics and small molecules that have the potential to directly or indirectly influence eosinophils, eosinophilic inflammation, and the consequences of eosinophil activation.
| S-EPMC4515571 | biostudies-literature
Project description:ObjectivesClinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE.MethodsWe conducted a cross-sectional study of contact registry data collected from 2015 to 2018. Statistical comparisons were made using chi-square (categorical measures) and the Mann-Whitney U test (continuous measures). Multivariable analyses were used to evaluate associations between treatment and feelings of isolation.ResultsOf the 715 reporting an EGID diagnosis (n = 525 EoE; n = 190 non-EoE EGID), a higher proportion of those with a non-EoE EGID reported more frequent specific and nonspecific gastrointestinal symptoms, including nausea, abdominal pain, diarrhea, constipation, and bloating (P < 0.01 for all). Participants with a non-EoE EGID were more likely to report higher frequency of fatigue, isolation, and deep muscle or joint pain (P < 0.01 for all). Specific food elimination and elemental formula treatments were associated with increased odds of more frequent (at least weekly) feelings of isolation for participants with EoE (adjusted odds rtaio [aOR]: 2.4; 95% confidence interval [CI]: 1.5--4.1 for specific food elimination and adjusted OR: 1.9; 95% CI: 1.2--3.3 for elemental formula).ConclusionsSignificant differences exist in the symptoms and comorbidities experienced between those with EoE versus non-EoE EGIDs. Additional investigation is needed to elucidate the factors that may contribute to the high disease burden of these poorly understood conditions.
| S-EPMC7574400 | biostudies-literature