Review

.2023 Aug:79:101858.

doi: 10.1016/j.trim.2023.101858. Epub 2023 May 24.

The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence

Maysoon T Al-Haideri¹, Reza Mannani², Roghayyeh Kaboli³, Farshad Gharebakhshi⁴, Shahram Darvishzadehdeldari⁵, Safa Tahmasebi⁶, Fatemeh Faramarzi⁷, Juan Carlos Cotrina-Aliaga⁸, Sahar Khorasani⁹, Mina Alimohammadi¹⁰, Mohammad Darvishi¹¹, Reza Akhavan-Sigari¹²

Affiliations

¹ Department of Physiotherapy, Cihan University, Erbil, Kurdistan Region, Iraq.
² Vascular Surgeon, Department of Surgery, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
³ Pathologist, Mother Laboratory, Zanjan, Iran.
⁴ Department of Radiology, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Department of Health Sciences, University of York, Heslington, York YO10 5DD, United Kingdom.
⁶ Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁸ Faculty of Human Medicine, Universidad Privada San Juan Bautista, Chincha, Peru.
⁹ Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mina.alimohammadi11@gmail.com.
¹¹ Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran. Electronic address: darvishi1349@gmail.com.
¹² Department of Neurosurgery, University Medical Center Tuebingen, Germany; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Poland.

PMID:37236514
PMCID: PMC10205646
DOI: 10.1016/j.trim.2023.101858

Review

The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence

Maysoon T Al-Haideri et al. Transpl Immunol.2023 Aug.

.2023 Aug:79:101858.

doi: 10.1016/j.trim.2023.101858. Epub 2023 May 24.

Authors

Affiliations

¹ Department of Physiotherapy, Cihan University, Erbil, Kurdistan Region, Iraq.
² Vascular Surgeon, Department of Surgery, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
³ Pathologist, Mother Laboratory, Zanjan, Iran.
⁴ Department of Radiology, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Department of Health Sciences, University of York, Heslington, York YO10 5DD, United Kingdom.
⁶ Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁸ Faculty of Human Medicine, Universidad Privada San Juan Bautista, Chincha, Peru.
⁹ Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: mina.alimohammadi11@gmail.com.
¹¹ Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran. Electronic address: darvishi1349@gmail.com.
¹² Department of Neurosurgery, University Medical Center Tuebingen, Germany; Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Poland.

PMID:37236514
PMCID: PMC10205646
DOI: 10.1016/j.trim.2023.101858

Abstract

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.

Keywords: Antibody level; COVID-19; Immune-mediated inflammatory diseases (IMIDs); Methotrexate (MTX); T cell response.

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Conflict of interest statement

Declaration of Competing Interest The authors declared that they have no competing interests.

Figures

**Fig. 1**
The diagram of study identification and selection.

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The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence

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The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence

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