Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

REsponses to COVid-19 vaccinE IsRaeli IBD group (RECOVER); Michal Werbner; Moshe Dessau; Meital Gal-Tanamy

doi:10.1053/j.gastro.2021.10.029

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

REsponses to COVid-19 vaccinE IsRaeli IBD group (RECOVER), Michal Werbner, Moshe Dessau, Meital Gal-Tanamy

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti–tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA–Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non–anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

Original language	English
Pages (from-to)	454-467
Number of pages	14
Journal	Gastroenterology
Volume	162
Issue number	2
DOIs	https://doi.org/10.1053/j.gastro.2021.10.029
State	Published - Feb 2022

Bibliographical note

Publisher Copyright:
© 2022 AGA Institute

Funding

Conflicts of interest Iris Dotan: Consultation/advisory board: Abbvie, Arena, Cambridge Healthcare, Celltrion, Celgene/BMS, Ferring, Janssen, MSD, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, and Takeda; and Speaking/teaching: Abbvie, Celltrion, Celgene/BMS, Ferring, Falk Pharma, Janssen, MSD, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sandoz, and Takeda. Ariella Bar-Gil Shitrit: Grant support from Takeda and Janssen, consultancy and lectures fees from Takeda, Janssen, Abbvie, Pfizer, Neopharm, and BMS. Eran Zittan has received research support and consulting fees from Janssen, Abbvie, Takeda, Neopharm, Celgene, and Pfizer. The remaining authors disclose no conflicts. We thank study participants for their effort and time. The Israeli IBD Society and Israeli GI Association are thanked for their support, and Dr Naim Abu-Freha for specific efforts to promote the study. The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust. The Crohn's and Colitis Foundation of Israel, the European Federation of Crohn's and Colitis Associations, and the AMICI group are thanked for partially funding the study and supporting recruitment efforts. We thank Kawsar Kaboub and Hanan Abu Taha from the Mucosal Immunology Laboratory at the Felsenstein Medical Research Center for their scientific contribution. This study was performed in collaboration with the Israeli Ministry of Health. Natalia T. Freund acknowledges the kind support of L. Cohen and the Milner Foundation. We thank study participants for their effort and time. The Israeli IBD Society and Israeli GI Association are thanked for their support, and Dr Naim Abu-Freha for specific efforts to promote the study. The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust. The Crohn's and Colitis Foundation of Israel, the European Federation of Crohn's and Colitis Associations, and the AMICI group are thanked for partially funding the study and supporting recruitment efforts. We thank Kawsar Kaboub and Hanan Abu Taha from the Mucosal Immunology Laboratory at the Felsenstein Medical Research Center for their scientific contribution. This study was performed in collaboration with the Israeli Ministry of Health. Natalia T. Freund acknowledges the kind support of L. Cohen and the Milner Foundation. Hadar Edelman-Klapper, MD, PhD (Data curation: Lead; Formal analysis: Supporting; Methodology: Supporting; Writing ? original draft: Lead), Eran Zittan, MD (Data curation: Lead), Ariella Bar-Gil Shitrit, MD (Data curation: Lead), Keren Masha Rabinowitz, PhD (Conceptualization: Supporting; Formal analysis: Lead; Methodology: Supporting; Writing ? review & editing: Supporting), Idan Goren, MD (Data curation: Supporting), Irit Avni-Biron, MD (Data curation: Supporting), Jacob E. Ollech, MD (Data curation: Supporting), Lev Lichtenstein, MD (Data curation: Supporting), Hagar Banai-Eran, MD (Data curation: Supporting), Henit Yanai, MD (Data curation: Supporting), Yifat Snir, MD (Data curation: Supporting), Maor H. Pauker, PhD (Conceptualization: Supporting; Data curation: Supporting;, Methodology: Supporting; Project administration: Lead), Adi Friedenberg, BPT (Conceptualization: Supporting; Data curation: Equal; Project administration: Equal), Adva Levy-Barda, PhD (Data curation: Supporting), Arie Segal, MD (Data curation: Supporting), Yelena Broitman, MD (Data curation: Supporting), Eran Maoz, MD (Data curation: Supporting), Baruch Ovadia, MD (Data curation: Supporting), Maya Aharoni Golan, MD (Data curation: Supporting), Eyal Shachar, MD (Data curation: Supporting), Shomron Ben-Horin, MD (Data curation: Supporting), Tsachi-Tsadok Perets, PhD (Data curation: Supporting), Haim Ben Zvi, PhD (Data curation: Supporting), Rami Eliakim, MD (Data curation: Supporting), Sophy Goren, BSc (Data curation: Equal; Formal analysis: Supporting), Michal Navon, BMs (Data curation: Supporting; Formal analysis: Supporting), Noy Krugliak, BSc (Data curation: Supporting; Formal analysis: Supporting), Michal Werbner, PhD (Data curation: Supporting; Formal analysis: Supporting), Joel Alter, PhD (Data curation: Supporting; Formal analysis: Supporting), Moshe Dessau, PhD (Data curation: Supporting; Formal analysis: Supporting), Meital Gal-Tanamy, PhD (Data curation: Supporting; Formal analysis: Equal; Funding acquisition: Supporting; Methodology: Equal; Writing ? review & editing: Supporting), Natalia T. Freund, PhD (Data curation: Supporting; Formal analysis: Equal; Funding acquisition: Supporting; Methodology: Equal; Writing ? review & editing: Supporting), Dani Cohen, PhD (Data curation: Supporting; Formal analysis: Lead; Writing ? review & editing: Supporting), Iris Dotan, MD (Conceptualization: Lead; Funding acquisition: Lead; Methodology: Lead; Supervision: Lead; Writing ? review & editing: Lead) Conflicts of interest Iris Dotan: Consultation/advisory board: Abbvie, Arena, Cambridge Healthcare, Celltrion, Celgene/BMS, Ferring, Janssen, MSD, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, and Takeda; and Speaking/teaching: Abbvie, Celltrion, Celgene/BMS, Ferring, Falk Pharma, Janssen, MSD, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sandoz, and Takeda. Ariella Bar-Gil Shitrit: Grant support from Takeda and Janssen, consultancy and lectures fees from Takeda, Janssen, Abbvie, Pfizer, Neopharm, and BMS. Eran Zittan has received research support and consulting fees from Janssen, Abbvie, Takeda, Neopharm, Celgene, and Pfizer. The remaining authors disclose no conflicts. Funding The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust # G-2101-04950 (Iris Dotan). The Crohn's and Colitis Foundation of Israel and the European Federation of Crohn's and Colitis Associations partially supported the study. Natalia T. Freund and Meital Gal-Tanamy are funded by Israel Science Foundation (ISF) Coronavirus grant #3711/20. Natalia T. Freund is funded by ISF grant #1422/18. Meital Gal-Tanamy is funded by ISF grant #2475/19. Moshe Dessau is funded by ISF grant #401/18. Funding The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust # G-2101-04950 (Iris Dotan). The Crohn's and Colitis Foundation of Israel and the European Federation of Crohn's and Colitis Associations partially supported the study. Natalia T. Freund and Meital Gal-Tanamy are funded by Israel Science Foundation (ISF) Coronavirus grant #3711/20. Natalia T. Freund is funded by ISF grant #1422/18. Meital Gal-Tanamy is funded by ISF grant #2475/19. Moshe Dessau is funded by ISF grant #401/18.

Funders	Funder number
Adva Levy-Barda
Baruch Ovadia
Crohn's and Colitis Foundation of Israel
European Federation of Crohn's and Colitis Associations
Falk Pharma
Hagar Banai-Eran
Haim Ben Zvi
IBD Society
Irit Avni-Biron
Israeli GI Association
Keren Masha Rabinowitz
Meital Gal-Tanamy
Michal Navon
Milner Foundation
Moshe Dessau
Mucosal Immunology Laboratory
Shomron Ben-Horin
Sophy Goren
Bristol-Myers Squibb
Pfizer	G-2101-04950
AbbVie
Leona M. and Harry B. Helmsley Charitable Trust
Takeda Pharmaceutical Company
Milner Foundation
Israel Science Foundation	2475/19, 1422/18, 401/18, 3711/20
Ferring Pharmaceuticals
Ministry of Health, State of Israel

Keywords

COVID-19
Serologic Response
Vaccine
mRNA-BNT162b2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1053/j.gastro.2021.10.029

Cite this

@article{c625d457833b40f096fa7397baeb2eb3,

title = "Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα",

abstract = "Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti–tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA–Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non–anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.",

keywords = "COVID-19, Serologic Response, Vaccine, mRNA-BNT162b2",

author = "{REsponses to COVid-19 vaccinE IsRaeli IBD group (RECOVER)} and Hadar Edelman-Klapper and Eran Zittan and {Bar-Gil Shitrit}, Ariella and Rabinowitz, {Keren Masha} and Idan Goren and Irit Avni-Biron and Ollech, {Jacob E.} and Lev Lichtenstein and Hagar Banai-Eran and Henit Yanai and Yifat Snir and Pauker, {Maor H.} and Adi Friedenberg and Adva Levy-Barda and Arie Segal and Yelena Broitman and Eran Maoz and Baruch Ovadia and Golan, {Maya Aharoni} and Eyal Shachar and Shomron Ben-Horin and Perets, {Tsachi Tsadok} and {Ben Zvi}, Haim and Rami Eliakim and Revital Barkan and Sophy Goren and Michal Navon and Noy Krugliak and Michal Werbner and Joel Alter and Moshe Dessau and Meital Gal-Tanamy and Freund, {Natalia T.} and Dani Cohen and Iris Dotan",

note = "Publisher Copyright: {\textcopyright} 2022 AGA Institute",

year = "2022",

month = feb,

doi = "10.1053/j.gastro.2021.10.029",

language = "אנגלית",

volume = "162",

pages = "454--467",

journal = "Gastroenterology",

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T1 - Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

AU - REsponses to COVid-19 vaccinE IsRaeli IBD group (RECOVER)

AU - Edelman-Klapper, Hadar

AU - Zittan, Eran

AU - Bar-Gil Shitrit, Ariella

AU - Rabinowitz, Keren Masha

AU - Goren, Idan

AU - Avni-Biron, Irit

AU - Ollech, Jacob E.

AU - Lichtenstein, Lev

AU - Banai-Eran, Hagar

AU - Yanai, Henit

AU - Snir, Yifat

AU - Pauker, Maor H.

AU - Friedenberg, Adi

AU - Levy-Barda, Adva

AU - Segal, Arie

AU - Broitman, Yelena

AU - Maoz, Eran

AU - Ovadia, Baruch

AU - Golan, Maya Aharoni

AU - Shachar, Eyal

AU - Ben-Horin, Shomron

AU - Perets, Tsachi Tsadok

AU - Ben Zvi, Haim

AU - Eliakim, Rami

AU - Barkan, Revital

AU - Goren, Sophy

AU - Navon, Michal

AU - Krugliak, Noy

AU - Werbner, Michal

AU - Alter, Joel

AU - Dessau, Moshe

AU - Gal-Tanamy, Meital

AU - Freund, Natalia T.

AU - Cohen, Dani

AU - Dotan, Iris

PY - 2022/2

Y1 - 2022/2

N2 - Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti–tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA–Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non–anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

AB - Background & Aim: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti–tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA–Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). Methods: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. Results: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non–anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non–anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

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KW - Serologic Response

KW - Vaccine

KW - mRNA-BNT162b2

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Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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