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Anti-TNF Exposure during Pregnancy in Crohn's Disease Patients.

ABSTRACT: Inflammatory bowel disease (IBD) affects young people of reproductive age. Therefore, a broad discussion is needed about the possible disease effects in pregnancy, as well as the risks of fetal exposure to the medications used, especially biological therapy. This study aimed to describe the management of 4 Crohn's disease patients who received anti-TNF therapy during pregnancy and present a literature review. We reported 4 cases composed of young women who became pregnant while receiving anti-TNF agents. The patients presented a satisfactory response to the clinical treatment and the pregnancies progressed without complications. We did not observe maternal or embryonic toxicity, or unfavorable outcomes. The available data point to inflammatory activity as the main risk factor for unfavorable gestational evolution to date, and showed anti-TNF therapy to be safe during pregnancy and breastfeeding. However, the benefits and risks must be discussed with the patient and management decisions should be taken on an individual basis.

SUBMITTER: Silva EFC

PROVIDER: S-EPMC6244106 | biostudies-other | 2018 Sep-Dec

REPOSITORIES: biostudies-other

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Anti-TNF Exposure during Pregnancy in Crohn's Disease Patients.

Silva Elen Farinelli de Campos EFC Baima Júlio Pinheiro JP de Barros Jaqueline Ribeiro JR Renosto Fernanda Lofiego FL de Sibia Carina de Fatima CF Saad-Hossne Rogério R Sassaki Ligia Yukie LY

Case reports in gastroenterology 20180901 3

Inflammatory bowel disease (IBD) affects young people of reproductive age. Therefore, a broad discussion is needed about the possible disease effects in pregnancy, as well as the risks of fetal exposure to the medications used, especially biological therapy. This study aimed to describe the management of 4 Crohn's disease patients who received anti-TNF therapy during pregnancy and present a literature review. We reported 4 cases composed of young women who became pregnant while receiving anti-TN ...[more]

PMID: 30483038

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Project description:BackgroundAnti-TNF medications are the first-line treatment for Crohn's Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.MethodsGSE16879, GSE111761, and GSE52746 retrieved from the GEO database. Unbiased differentially expressed genes (DEGs) were discovered utilizing the limma and RobustRankAggreg (RRA) tools. Then, we used weighted gene co-expression network analysis (WGCNA) to identify the module most strongly associated with non responders and subjected this module to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis with overlapping genes of the DEGs. GSEA analysis applied to check the results of GO and KEGG. Using the Cytoscape program, the protein-protein interaction (PPI) network was constructed. The software's MCODE addon and CytoHubba addon was used to find the most important modules and the hub genes. Subsequently, we employed reverse transcription-polymerase chain reaction (RT-PCR) to confirm hub gene expression from mucosal biopsy specimens.ResultsThere were a total of 142 genes co-upregulated and 65 genes co-downregulated. According to the WGCNA analysis, 42 genes were duplicated inside the light cyan module. GO and KEGG enrichment analyses of overlapped genes in nonresponders demonstrated an increase in the expression of genes associated with inflammation and immune response, consistent with GSEA results. The PPI network was constructed using 41 protein nodes and 177 edges. After validation, 8 of the top 10 genes were verified to be differentially expressed.ConclusionOur investigation is the first to integrate three CD databases after the anti-TNF medication treatment. We identified IL1B, CCL4, CXCL1, CXCL10, CCL3, CSF3, TREM1, and IL1RN as potential therapeutic targets for patients whose anti-TNF treatment failed.

Project description:BackgroundUstekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi).MethodsPatients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort.FindingsA total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423).InterpretationUstekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients.FundingNational Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

Project description:Abstract Background and Aim TL1A (TNFSF15) is a major Crohn's disease (CD) susceptibility gene, especially in the East Asian population, and is also known to be associated with some clinical phenotypes, such as stricturing and penetrating behavior. This study aims to investigate the association between TL1A genotype and the long?term therapeutic outcomes of infliximab and adalimumab in Japanese CD patients. Methods We investigated 119 biologic?naïve CD patients treated with infliximab or adalimumab. TL1A ?358C/T (rs6478109) was genotyped as a tag single nucleotide polymorphism (SNP) for CD risk or nonrisk haplotype of TL1A (the ?358C allele is a risk allele for CD development). We compared the long?term therapeutic outcomes of anti?tumor necrosis factor (TNF) antibodies between the TL1A ?358C/C group and the C/T+T/T group. Results Sixty?nine cases (58.0%) were homozygous for the risk allele (TL1A ?358C/C group), and 50 cases (42.0%) were heterozygous for the risk allele or homozygous for the protective allele (TL1A ?358C/T+T/T group). No significant differences were found in the cumulative retention rates and the relapse?free survival between the TL1A genotypes. However, the surgery?free survival was significantly lower in the TL1A ?358C/C group than in the C/T+T/T group (log?rank test, P?<?0.05). Multivariate analysis showed that TL1A ?358C/C was identified as an independent risk factor for surgery (hazard ratio, 4.67; 95% confidence interval, 1.39–22.1; P = 0.025). Conclusion An association was found between the TL1A genotype and the therapeutic outcomes of anti?TNF therapy. Our data indicate that the design of customized therapy with anti?TNF antibodies using TL1A genomic information could be effective in the future. In this study, we investigated the association between TL1A genotype and the long?term therapeutic outcomes of infliximab and adalimumab in Crohn's disease (CD) patients. We investigated 119 biologic?naïve CD patients treated with infliximab or adalimumab and found an association between the TL1A genotype and surgery?free survival during anti?tumor necrosis factor (TNF) therapy. The patients whose genotypes are homozygous for the TL1A ?358C (risk allele of CD development) show lower surgery?free survival with anti?TNF treatment.

Project description:Background and aimsAnti-tumour necrosis factor [TNF] treatment failure in patients with inflammatory bowel disease [IBD] is common and frequently related to low drug concentrations. In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14.MethodsDNA methylation from 1104 whole blood samples from 385 patients in the Personalised Anti-TNF Therapy in Crohn's disease [PANTS] study were assessed using the Illumina EPIC Beadchip [v1.0] at baseline and weeks 14, 30, and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 if they were assessed at subsequent time points and were not in remission at week 30 or 54 [infliximab n = 99, adalimumab n = 94], with patients who responded at week 14 and when assessed at subsequent time points were in remission at week 30 or 54 [infliximab n = 99, adalimumab n = 93].ResultsOverall, between baseline and week 14, we observed 4999 differentially methylated positions [DMPs] annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses. Epigenome-wide association [EWAS] analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at Week 14. Of these, 125 DMPs demonstrated shared associations with other common traits [proportion of shared CpGs compared with DMPs] including body mass index [23.2%], followed by C-reactive protein [CRP] [11.5%], smoking [7.4%], alcohol consumption per day [7.1%], and IBD type [6.8%]. EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients [Spearman's rho = -0.94, p <0.001].ConclusionBaseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy.

Dataset Information

Anti-TNF Exposure during Pregnancy in Crohn's Disease Patients.

Publications

Anti-TNF Exposure during Pregnancy in Crohn's Disease Patients.

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