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Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

ABSTRACT: Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

SUBMITTER: Rabinowitz KM

PROVIDER: S-EPMC9330864 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Rabinowitz Keren Masha KM Navon Michal M Edelman-Klapper Hadar H Zittan Eran E Bar-Gil Shitrit Ariella A Goren Idan I Avni-Biron Irit I Ollech Jacob E JE Lichtenstein Lev L Banai-Eran Hagar H Yanai Henit H Snir Yifat Y Pauker Maor H MH Friedenberg Adi A Levy-Barda Adva A Segal Arie A Broitman Yelena Y Maoz Eran E Ovadia Baruch B Aharoni Golan Maya M Shachar Eyal E Ben-Horin Shomron S Maharshak Nitsan N Mor Michal M Ben Zvi Haim H Eliakim Rami R Barkan Revital R Sharar-Fischler Tali T Goren Sophy S Krugliak Noy N Pichinuk Edward E Mor Michael M Werbner Michal M Alter Joel J Abu-Taha Hanan H Kaboub Kawsar K Dessau Moshe M Gal-Tanamy Meital M Cohen Dani D Freund Natalia T NT Dotan Iris I On Behalf Of The Responses To Covid-Vaccine Israeli Ibd

Vaccines 20220726 8

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patient ...[more]

PMID: 35893835

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Project description:Anti-TNF-alpha (anti-TNFα) therapies have transformed the care and management of inflammatory bowel disease (IBD). However, they are expensive and ineffective in greater than 50% of patients, and they increase the risk of infections, liver issues, arthritis, and lymphoma. With 1.6 million Americans suffering from IBD and global prevalence on the rise, there is a critical unmet need in the use of anti-TNFα therapies: a test for the likelihood of therapy response. Here, as a proof-of-concept, we present a multi-mRNA signature for predicting response to anti-TNFα treatment to improve the efficacy and cost-to-benefit ratio of these biologics. We surveyed public data repositories and curated four transcriptomic datasets (n = 136) from colonic and ileal mucosal biopsies of IBD patients (pretreatment) who were subjected to anti-TNFα therapy and subsequently adjudicated for response. We applied a multicohort analysis with a leave-one-study-out (LOSO) approach, MetaIntegrator, to identify significant differentially expressed (DE) genes between responders and non-responders and then used a greedy forward search to identify a parsimonious gene signature. We then calculated an anti-TNFα response (ATR) score based on this parsimonious gene signature to predict responder status and assessed discriminatory performance via an area-under-receiver operating-characteristic curve (AUROC). We identified 324 significant DE genes between responders and non-responders. The greedy forward search yielded seven genes that robustly distinguish anti-TNFα responders from non-responders, with an AUROC of 0.88 (95% CI: 0.70-1). The Youden index yielded a mean sensitivity of 91%, mean specificity of 76%, and mean accuracy of 86%. Our findings suggest that there is a robust transcriptomic signature for predicting anti-TNFα response in mucosal biopsies from IBD patients prior to treatment initiation. This seven-gene signature should be further investigated for its potential to be translated into a predictive test for clinical use.

Dataset Information

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Publications

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Similar Datasets

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