Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Connolly, Cynthia; Paik, Julie J

doi:10.1016/s2665-9913(21)00217-4

Cited by 6 publications

(10 citation statements)

References 10 publications

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“…The immunosuppressants used to treat mice have been associated with altering counts and percentages of key immune cell populations in numerous previous research studies (22)(23)(24)(25)(26)(27)(28)(29)(30). These suppressants, but most notably in cyclophosphamide, a drug that is known to dysregulate immune cell populations and, as our research reinforces, greatly depletes B cell populations.…”

Section: Immune Suppression Alters the Immune Landscape Of Spike Protein-immunized Micesupporting

confidence: 52%

“…In this study, we investigated the effects of five widely used immunosuppressant drugs that target different pathways of the immune responses, and if these effects could be modulated following changes to immunosuppressant regimens in mouse models (Table 1). Specifically, we investigated: cyclophosphamide (CYC, a potent drug known to deplete immune cells, which has been shown to impair vaccine responses(25)); leflunomide (LEF, a disease-modifying antirheumatic drug, or DMARD, that interferes with immune cell replication and has been shown to inhibit IgE antibody response (26, 27)); methotrexate (MTX, a potent drug used in multiple disease models which inhibits the activities of multiple enzymes critical for immune cell function and has been shown to interfere in multiple vaccination models (22-24, 28, 29)); methylprednisolone (MP, a commonly used corticosteroid that may alter opsonophagocytic killing of pathogens by immune cells(23)); and mycophenolate mofetil (MM, an inhibitor of purine biosynthesis shown to inhibit antibody responses (30)). We determined that all drugs significantly reduced antibody response to SARS-CoV-2 spike protein vaccination in mice when administered in doses and routes of administration based on established mouse models (22-30) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…to inhibit IgE antibody response (26,27)); methotrexate (MTX, a potent drug used in multiple disease models which inhibits the activities of multiple enzymes critical for immune cell function and has been shown to interfere in multiple vaccination models (22-24, 28, 29)); methylprednisolone (MP, a commonly used corticosteroid that may alter opsonophagocytic killing of pathogens by immune cells( 23)); and mycophenolate mofetil (MM, an inhibitor of purine biosynthesis shown to inhibit antibody responses (30)). We determined that all drugs significantly reduced antibody response to SARS-CoV-2 spike protein vaccination in mice when administered in doses and routes of administration based on established mouse models (22)(23)(24)(25)(26)(27)(28)(29)(30) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice

Ozdilek

et al. 2021

Preprint

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The COVID-19 pandemic dramatically demonstrated the need for improved vaccination strategies and therapeutic responses to combat infectious diseases. However, the efficacy of vaccines has not yet been demonstrated in combination with commonly used immunosuppressive drug regimens. We sought to determine how common pharmaceutical drugs used in autoimmune disorders can alter immune responses to the SARS-CoV-2 spike protein vaccination. We treated mice with five immunosuppressant drugs (cyclophosphamide, leflunomide, methotrexate, methylprednisolone, and mycophenolate mofetil), each with various mechanisms of action prior to and following immunization with SARS-CoV-2 spike protein. We assessed the functionality of antibody responses to spike protein and compared immune cell populations in mice that received no treatment with those that received continuous or temporarily suspended immune suppressive therapy. All tested immunosuppressants significantly reduced the antibody titers in serum and functional antibody response against SARS-CoV-2 spike protein in immunized mice. Temporarily halting selected immunosuppressants (methylprednisolone and methotrexate, but not cyclophosphamide) improved antibody responses significantly. Through proof-of-principle experiments utilizing a mouse model, we demonstrated that immune suppression in autoimmune disorders through pharmaceutical treatments may impair vaccine response to SARS-CoV-2, and temporary suspension of immunosuppressant treatment may be necessary to mount an effective antibody vaccine response. This work provides feasibility for future clinical assessment of the impact of immunosuppressants on vaccine efficacy in humans.

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Section: Immune Suppression Alters the Immune Landscape Of Spike Protein-immunized Micesupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice

Ozdilek

et al. 2021

Preprint

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“…The different available vaccines should also be tested to verify their usefulness in the case of people with autoimmune diseases and on individual immunomodulatory medications [25]. Patients who receive immunosuppressive treatment should receive the vaccine using the regular, not prolonged interval, vaccination schedule [26]. Additionally, considering a diminished humoral response and the possibility of a diminished cellular response to vaccination, especially in light of the emergence of new variants of concern of SARS-CoV-2 [23,24], along with other authors [6] we also stress the need to consider alternate vaccination strategies, such as additional vaccine doses, for MTX patients.…”

Section: Discussionmentioning

confidence: 99%

Humoral Response to SARS-CoV-2 Vaccine of a Patient Receiving Methotrexate Treatment and Implications for the Need of Monitoring

et al. 2021

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We report a case of monitoring the antibody response to the BioNTech–Pfizer vaccine of a 50-year-old female diagnosed with rheumatoid arthritis undergoing treatment with methotrexate (MTX). Antibody levels were measured 21 days after dose 1 (i.e., on the day of dose 2) and then 8, 14 and 30 days after dose 2 with Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics). Patient showed a negative result after dose 1 and had the serum sample retested using a LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin), which showed a positive result. Subsequent samples were tested using both assays. Antibody levels kept increasing but at a much slower rate than in patients not receiving any immunomodulatory therapies. Other research indicates that among patients with autoimmune diseases, those receiving disease-modifying antirheumatic drugs (DMARDs) have higher COVID-19 mortality than those treated with tumor necrosis factor inhibitors (TNFis). These results indicate the need for people with autoimmune diseases to be carefully observed following vaccinations, including testing of antibody levels, and treated as potentially at risk until the effect of vaccination is confirmed. The different available vaccines should also be tested to verify their usefulness in the case of people with autoimmune diseases and those who take different immunomodulatory medications.

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“…Тем не менее в исследовании S. K. Mahil и соавт. проводилась оценка гуморального и клеточного иммунного ответа на вакцину BNT162b2 (Pfizer-BioNTech) против COVID-19 у пациентов, принимающих метотрексат и препараты таргетной иммунотерапии, в сравнении со здоровыми добровольцами из контрольной группы [19,20]…”

Section: вакцинопрофилактика Covid-19 на фоне применения иммуносупрессоровunclassified

Induction of anti-SARS-CoV-2 immune reactions in immune compromised patients

Pogodina

Lobov

Ivanova

et al. 2021

Rossijskij bioterapevtičeskij žurnal

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The aim of the review is studying the immune response to the new coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus in different populations, including those with immunosuppression due to concomitant diseases or immunosuppressive therapy.The role of T cells in building up the anti-COVID-19 immunity is of special interest, particularly, when comparing T cell and antibody based immunity. A number of studies are focused on the effectiveness of T-cell immunity against SARS-CoV-2 infection, as well as on the resistance to re-infection. The decreased immunity associated with such illnesses as autoimmune diseases, non-autoimmune inflammations, and the effect of immunosuppressive drugs and obviously, different cancers increase the susceptibility to SARS-CoV-2 and COVID-19 development, and exacerbate the course of the disease.Several studies showed that patients with cancer are at risk of impaired immune response associated with a malignant neoplasm. The inefficient immune response was also shown in cancer patients receiving immunomodulatory therapy. However, some studies registered the specific immunogenicity after vaccination in patients with concomitant immunosuppression.Methotrexate is a folate antimetabolite. The drug can be used both in high doses as an antimetabolite in the antitumor therapy, and in low doses as an immunosuppressive agent in patients with autoimmune diseases. Therefore, the review also discusses a study that evaluated the humoral and cellular immune response to the BNT162b2 (PfizerBioNTech) anti-COVID-19 vaccine in patients receiving methotrexate. The rate of antibody production was lower in patients receiving methotrexate, though the level of T-cell response was similar in all groups studied.The review discussed immune compromised patients with cancer and hematological malignancies and patients living with HIV who had COVID-19. Most studies reported no significant differences of COVID-19 outcomes between major population and the patients with suppressed immune system.Hereby, the cell and humoral immune response in immune compromised patients is possible, however, additional studies are required to confirm these data.

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Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Cited by 6 publications

References 10 publications

Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice

Modulation of immunosuppressant drug treatment to improve SARS-CoV-2 vaccine efficacy in mice

Humoral Response to SARS-CoV-2 Vaccine of a Patient Receiving Methotrexate Treatment and Implications for the Need of Monitoring

Induction of anti-SARS-CoV-2 immune reactions in immune compromised patients

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