Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease

Orfanoudaki, Eleni; Foteinogiannopoulou, Kalliopi; Theodoraki, Eirini; Koutroubakis, Ioannis Ε.

doi:10.3390/jcm12072452

Cited by 3 publications

(1 citation statement)

References 158 publications

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“… 74 87 88 In steroid-refractory immune-related colitis, anti-Tumor Necrosis Factor (TNF)-α treatment with infliximab is often initiated, especially when the inflammation is severe (correlation TNF-α and inflammation), according to studies in IBD. 89 90 In contrast to the unspecific action of infliximab, vedolizumab has a specific effect in the intestinal tract by blocking the alpha4-beta7-integrin which is involved in homing of T cells to the intestinal tract. 60 75 91 92 In addition to modulating the immune system pathways, another approach for treating immune-related colitis is targeting the microbiome.…”

Section: Management Of Steroid-resistant Situations By Organ Site (Li...mentioning

confidence: 99%

Corticosteroid-resistant immune-related adverse events: a systematic review

Daetwyler,

Wallrabenstein,

König

et al. 2024

J Immunother Cancer

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Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient’s immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend—as first line treatment—(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.

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Section: Management Of Steroid-resistant Situations By Organ Site (Li...mentioning

confidence: 99%

Corticosteroid-resistant immune-related adverse events: a systematic review

Daetwyler,

Wallrabenstein,

König

et al. 2024

J Immunother Cancer

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Infliximab monitoring in Crohn’s disease: a neural network approach for evaluating disease activity and immunogenicity

Gomes,

Genaro,

Castro

et al. 2024

Therap Adv Gastroenterol

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Background: The treatment for Crohn’s disease (CD) has increasingly required the use of biological agents. Safe and affordable tests have led to the active implementation of therapeutic drug monitoring (TDM) in clinical practice, which, although not yet widely available across all health services, has been proven effective. Objective: To analyze serum infliximab (IFX) and antidrug antibody (ADA) levels in CD patients, compare two tests, as well as construct a prediction of neural network using a combination of clinical, epidemiological, and laboratory variables. Design: Cross-sectional observational study. Method: A cross-sectional observational study was conducted on 75 CD patients in the maintenance phase of IFX treatment. The participants were allocated into two groups: CD in activity (CDA) and in remission (CDR). Disease activity was defined by endoscopic or radiological criteria. Serum IFX levels were measured by enzyme-linked immunosorbent assay (ELISA) and rapid lateral flow assay; ADA levels were measured by ELISA. A nonparametric test was used for statistical analysis; p value of ⩽0.05 was considered significant. Differences between ELISA and rapid lateral flow results within the measurement range were assessed by the Wilcoxon test, Passing–Bablok regression, and Bland–Altman method. Prediction models were created using four neural network sets. Neural networks and performance receiver operating characteristic curves were created using the Keras package in Python software. Results: Most participants exhibited supratherapeutic IFX levels (>7 mg/mL). Both tests showed no difference in IFX levels between the CDA and CDR groups ( p > 0.05). The use of immunosuppressive therapy did not affect IFX levels ( p > 0.05). Only 14.66% of patients had ADA levels >5 AU/mL, and all ADA-positive participants exhibited subtherapeutic IFX levels in both tests. The median results of both tests showed significant differences and moderate agreement ( r = −0.6758, p < 0.001). Of the four neural networks developed, two showed excellent performance, with area under the curve (AUCs) of 82–92% and 100%. Conclusion: Most participants exhibited supratherapeutic IFX levels, with no significant serum level difference between the groups. There was moderate agreement between tests. Two neural network sets showed disease activity and the presence of ADA, noninvasively determined in patients using IFX by presenting an AUC of >80%.

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Establishment and Characterization of Patient-Derived Intestinal Organoids from Pediatric Crohn’s Disease Patients

An,

Huh,

et al. 2024

Pediatr Gastroenterol Hepatol Nutr

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Purpose This study aimed to establish and characterize patient-derived intestinal organoids (PDOs) from children with Crohn’s disease (CD). Methods To generate PDOs, endoscopic biopsy specimens were obtained from non-inflamed duodenal bulbs of normal controls and CD patients. To verify the presence of PDOs, histological staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses were performed. Results PDOs were successfully established in normal controls (n=2) and CD patients (n=2). Hematoxylin and eosin staining of formalin-fixed, paraffin-embedded PDO sections revealed crypt and villus structures, whereas immunofluorescence staining with EpCAM and DAPI confirmed the epithelial-specific architecture of the PDOs. RT-qPCR results revealed a significant increase in Lgr5 , Si , and Chga gene expression and a decrease in Olfm4 and Muc2 expression in CD patients compared to normal controls, suggesting altered stem cell activity and mucosal barrier function ( p <0.05). Conclusion We successfully established and characterized PDOs in children with CD, providing a valuable tool for understanding the pathophysiology of the disease and evaluating potential therapeutic approaches. The differential gene expression of PDOs in CD patients might be caused by the complex interplay between epithelial adaptation and inflammation in the intestinal epithelium.

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Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease

Cited by 3 publications

References 158 publications

Corticosteroid-resistant immune-related adverse events: a systematic review

Corticosteroid-resistant immune-related adverse events: a systematic review

Infliximab monitoring in Crohn’s disease: a neural network approach for evaluating disease activity and immunogenicity

Establishment and Characterization of Patient-Derived Intestinal Organoids from Pediatric Crohn’s Disease Patients

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