Tag Archives: #methotrexate

Patients Taking Methotrexate Respond Less Well to COVID-19 Vaccine (Medicine)

One-quarter of people who take the drug methotrexate for common immune system disorders—from rheumatoid arthritis to multiple sclerosis—mount a weaker immune response to a coronavirus disease (COVID-19) vaccine, a new study shows.

Published recently in Annals of the Rheumatic Diseases, the study addressed disorders that result when the immune system, meant to fight disease and drive healing, is triggered abnormally. This in turn causes inflammation, the pain and swelling that come as immune cells rush into damaged or infected tissue, but often in the wrong amount or context. Called immune-mediated inflammatory disorders, they are typically treated with drugs that reduce inflammation, including methotrexate.

Led by researchers at NYU Grossman School of Medicine, the new study looked specifically at patients’ responses to the Pfizer–BioNTech mRNA COVID-19 vaccine, which they measured by looking at the antibodies produced in each patient by the vaccine. Once injected into the body, vaccine ingredients are meant to trigger the production of antibodies, immune proteins that specifically glom onto this viral target protein, disabling it and tagging it for removal from the body.

The lower antibody response in patients who take methotrexate does not necessarily mean that these patients are not protected against COVID-19, cautions co-first study author Rebecca Haberman, MD, clinical instructor in the Department of Medicine at NYU Langone Health.

“It is most important to state that patients should not be concerned about our study findings as the majority of patients with immune system disorders are responding well to the mRNA vaccines,” Dr. Haberman says. “It is also possible that methotrexate is delaying, rather than preventing, an adequate immune response against COVID-19.”

Researchers have known that patients with rheumatoid arthritis who take methotrexate have a reduced response to seasonal flu vaccines. Because mRNA vaccines use a new mechanism of action that patients with these common immune disorders have not seen before, the researchers wanted to determine how well these patients are protected.

The research was conducted at NYU Langone and at Friedrich-Alexander University Erlangen Nuremberg in Germany and enrolled healthy people and patients treated for common immune-mediated disorders, including rheumatoid arthritis, psoriatic arthritis, and psoriasis. Study participants received two doses of Pfizer–BioNTech mRNA COVID-19 vaccine. The researchers analyzed blood samples to determine the amount of antibodies patients produced after receiving the vaccine and measured the activation of key immune system cells, including CD8 killer T cells, which are generated as part of the body’s immune response.

The researchers found that more than 90 percent of healthy subjects and patients taking drugs other than methotrexate to control inflammation in both the New York and German study groups mounted strong antibody responses. Patients with immune-mediated inflammatory disorders who were taking methotrexate achieved an adequate response in only 62 percent of cases. Similarly, while healthy patients and those with common immune disorders who were taking anti-inflammatory drugs other than methotrexate produced CD8 T cells, patients taking methotrexate did not show an increase in CD8 T cell activation after vaccination.

“More research is needed to understand why such a significant proportion of people with common immune disorders who take methotrexate have deficiencies in mounting an antibody and cellular response,” says study co-senior author Jose U. Scher, MD, an associate professor in the Department of Medicine at NYU Langone. “This may not necessarily mean that the vaccine is not efficacious, but that alternate vaccine strategies need to be investigated.”

These alternate vaccine strategies include potentially discontinuing methotrexate during the time these patients receive the vaccine, changing the dosage of methotrexate, or possibly administering a booster shot to the vaccine, says Dr. Scher, who is also director of the Psoriatic Arthritis Center at NYU Langone. The research team is currently leading studies to determine the best course of action for these patients.

This work was supported by National Institutes of Health grants R01 AR074500, T32 AR069515, and UM1 AI148574; a Rheumatology Research Foundation Scientist Development Award; the Bloomberg Philanthropies COVID-19 Initiative; the Pfizer COVID-19 Competitive Grant Program; The Beatrice Snyder Foundation; and The Riley Family Foundation.

Dr. Scher has served as a consultant for Janssen, Novartis, Pfizer, Bristol Myers Squibb, Sanofi and UCB, and Abbvie, and he has received funding for investigator-initiated studies from Novartis, Sanofi, Pfizer, and Janssen. Dr. Haberman has received consulting fees from Janssen. Study co-investigators Peter M. Izmirly, MD, has received consulting fees from GSK and Momenta/Janssen; and Steven B. Abramson, MD, has received grants from Johnson and Johnson. Study co-corresponding author Mark J. Mulligan, MD, has received grants from Eli Lilly, Pfizer, and Sanofi and personal fees from Meissa Vaccines. All of these relationships are being managed in accordance with the policies and procedures of NYU Langone.

In addition to Dr. Scher, Dr. Haberman, Dr. Izmirly, Dr. Abramson, and Dr. Mulligan, other NYU Langone investigators are co-first authors Ramin Herati, MD, and Marie Samanovic-Golden, MD; and study co-investigators Rebecca B. Blank, MD, PhD; Michael Tuen, PhD; Sergei B. Koralov, PhD; Joseph R. Allen; Rochelle L. Castillo, MD; Amber R. Cornelius; Paula J. Rackoff, MDGary E. Solomon, MDSamrachana Adhikari, PhDNatalie E. Azar, MDPamela Rosenthal, MDJonathan Samuels, MDBrian D. Golden, MD; and Soumya M. Reddy, MD. Other researchers involved in the study are co-corresponding author Georg Schett, MD, PhD; co-first author David Simon, MD; and study co-investigators Raja Atreya, MD; Koray Tascilar, MD; and Markus Neurath, MD, at Friedrich-Alexander University Erlangen Nuremberg.

Featured image: MANUSAPON KASOSOD/GETTY


Reference: Haberman RH, Herati R, Simon D, et alMethotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory diseaseAnnals of the Rheumatic Diseases Published Online First: 25 May 2021. doi: 10.1136/annrheumdis-2021-220597


Provided by NYU Langone

Methotrexate Users Have A Reduced Immune Response to mRNA COVID-19 Vaccine (Medicine)

Methotrexate is commonly taken by patients with rheumatoid arthritis, psoriasis and other autoimmune diseases

Up to a third of patients taking methotrexate – a common treatment for immune mediated inflammatory conditions such as rheumatoid arthritis and psoriasis/psoriatic arthritis – failed to achieve an adequate immune response to mRNA COVID-19 vaccines in a small study accepted for publication in the journal Annals of Rheumatic Diseases.

While mRNA COVID-19 vaccines have been shown to produce an effective immune response in over 90% of healthy adults in clinical trials, it is unknown whether the immune response is as robust in patients with immune-mediated inflammatory diseases (IMID) who may also be taking immunomodulatory medications.

The authors assessed the immune response to the mRNA Pfizer-BioNTech COVID-19 vaccine in 82 patients with immune-mediated inflammatory diseases (mainly psoriasis/psoriatic arthritis and rheumatoid arthritis) receiving methotrexate or an alternative immunomodulator (mainly TNF inhibitors and other biologics) at two centres – New York University Langone Health (New York, USA) and FAU Erlangen-Nuremberg and Universitatsklinikum Erlangen (Erlangen, Germany).

The study found that the Pfizer-BioNTech vaccine induced adequate antibody levels in up to a third fewer patients on methotrexate, when compared with healthy participants and patients with IMIDs on the other immunomodulatory drugs.

Adequate antibody levels were produced in over 90% of the 208 healthy participants and 37 patients on biologic or non-methotrexate oral treatments, but in only 62% of the 45 patients taking methotrexate.

Furthermore, while the vaccination induced activated CD8+ T cell responses in healthy participants and patients with immune-mediated inflammatory diseases not on methotrexate, this same induction was not seen in those patients on methotrexate. T cells are another part of the body’s immune defence system.

This is an observational study, and as such, can’t establish causality. The authors also acknowledge that the study had a small sample size, only assessed one type of mRNA COVID-19 vaccine, and could have included patients with previously asymptomatic COVID-19 infections.

They also point out that IMID patients on methotrexate were generally older than the comparison group (average age 63 vs 49) which may potentially explain some differences in immunogenicity.

Additionally, the authors emphasize that “it is not yet clear what level of immunogenicity is representative of vaccine efficacy.”

They go on to note that “although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with immune-mediated inflammatory diseases taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.”

Methotrexate, for example, has previously been shown to reduce the immune response to the influenza vaccine.

The authors add: “Our results suggest that the optimal protection of patients with IMID against COVID-19 will require further studies to determine whether additional doses of vaccine, dose modification of methotrexate, or even temporary discontinuation of this drug can boost immune response as has been demonstrated for other viral vaccines in this patient population.”


Reference: Haberman RH, Herati R, Simon D, et al. Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory diseaseAnnals of the Rheumatic Diseases Published Online First: 25 May 2021. doi: 10.1136/annrheumdis-2021-220597


Provided by BMJ

Schizophrenia May be Similar to Immune Disorders, Show Scientists (Psychiatry)

A study by clinical scientists at the University of Manchester has shown that schizophrenia may—in some part—be caused by disordered functioning of the immune system.

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The first ever trial in schizophrenia of the powerful immune suppressant drug, Methotrexate, produced what the team described as ‘promising’ effects on what are known as positive symptoms, such as hearing voices.

Though the team stress the sample size was too small to show if Methotrexate could work as an add-on treatment for schizophrenia, they found a ‘puzzling’ therapeutic effect on symptoms of early schizophrenia.

And that, they argue, warrants further investigation.

The findings published in the Journal of Translational Psychiatry shed new light on the devastating and difficult to treat condition, which causes distress and disability worldwide.

Schizophrenia is categorized by so called ‘positive symptoms’ such as hearing voices (hallucinations) and ‘negative symptoms’ (disordered thinking, poor motivation, poor social function).

Negative symptoms, which contribute significantly to the disability associated with schizophrenia are hard to treat with currently available medication.

The study was funded by the Stanley Medical Research Institute in the United States in collaboration with the Pakistan Institute of Living and Learning.

The trial took place in Pakistan, led by Professor Imran Chaudhry from The University of Manchester who after years of service to the NHS relocated to Pakistan to continue to practice psychiatry.

The lack of available treatments for these symptoms encouraged Professor Chaudhry’s team to investigate new treatment options for schizophrenia.

Methotrexate is often used to treat inflammatory diseases such as rheumatoid arthritis and Crohn’s disease.

Inflammatory and autoimmune conditions are more common in patients with schizophrenia, possibly indicating that there is a shared underlying cause to these diseases.

“Methotrexate is thought to help treat autoimmune disorders by resetting the way T cells—an important part of the immune system—work,” said Professor Chaudhry.

“This action on the central nervous system may account for the improvement in symptoms we found in our study,” he added.

They used a low 10mg dose of the drug, which was given alongside the patients’ routine psychiatric medication.

No significant side-effects were reported by the patients taking Methotrexate, suggesting it was relatively well tolerated.

Nusrat Husain, Professor of Psychiatry and Director of Research in Global Mental Health at The University of Manchester added: “We used the lowest clinically effective dose in autoimmune disorders which often needs to be increased so higher doses could produce a more powerful effect in schizophrenia.

“However, the health risks of methotrexate are substantial and require careful monitoring which is why we would rule out large unfocussed trials.”

Psychiatrist Dr. Omair Husain, who is an honorary researcher at The University of Manchester and an Assistant Professor based at The University of Toronto said: “Immune systems could be involved in schizophrenia and that raises fascinating questions.

“Perhaps one day we might be able to identify subsets of people with schizophrenia who may respond to treatments that act on the immune system.

“The small, unexpected effect we found in our study warrants further investigation which we now believe is feasible.

“Future work needs to focus on identifying these subgroups possibly through studies that use advanced brain imaging techniques and state of the art immune profiling techniques.”

Reference: I. B. Chaudhry et al. A randomized clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis, Translational Psychiatry (2020). DOI: 10.1038/s41398-020-01095-8 https://www.nature.com/articles/s41398-020-01095-8

Provided by University of Manchester