Infectious Disease

NIH Opens Study to Booster COVID-19 in Patients With Autoimmune Disease

September 01, 2021

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Calabrese reports consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Horizon, Janssen, Kiniksa, Eli Lilly & Co., Pfizer, Sanofi-Regeneron and UCB as well as consulting fees from AbbVie, Bristol Myers Squibb, Crescendo Genentech, Horizon, Sanofi and UCB.


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The NIH has started a clinical trial to investigate antibody responses to a COVID-19 vaccine booster dose in patients with autoimmune diseases who did not respond to the initial vaccination schedule.

According to an NIH press release, the Phase 2 study will also investigate whether interrupting immunosuppressive therapy for autoimmune diseases improves the antibody response to an additional dose of COVID-19 vaccine in this population.

“The NIH has started an important study examining the effects of immunosuppressive drugs on amplification and holding time, including mycophenolate mofetil or mycophenolic acid, methotrexate or B-cell-depleting drugs, in order to evaluate the effects on antibody response in a randomized study” , Leonard Calabrese, DO, said Healio Rheumatology. Source: Adobe Stock

“The NIH has started an important study in which the effects of immunosuppressive boosters and stop drugs such as mycophenolate mofetil or mycophenolic acid, methotrexate or B-cell-depleting drugs are being investigated in order to evaluate the effects on the antibody reaction in a randomized study.” Leonard Calabrese, DO, Professor of Medicine at Cleveland Clinic Lerner College of Medicine at Case Western Reserve University and RJ Fasenmyer Chair of Clinical Immunology at Cleveland Clinic versus Healio Rheumatology.

“Unfortunately, this is a real-time problem for patients with immune-mediated inflammatory diseases (IMIDs), including many rheumatic diseases, dermatological diseases, multiple sclerosis and other neuroimmunological diseases, as well as inflammatory bowel disease, among others,” he added.

Big month for the booster shot

August brought an avalanche of news of the possible use of a COVID-19 vaccine booster for certain patients.

On August 12, the FDA announced an update to its emergency approval for the Pfizer-BioNTech and Moderna messenger RNA vaccines, which will add a third dose “to certain immunocompromised individuals, particularly those who have received solid organ transplants or have been diagnosed with disease. they are considered to be equivalent in terms of immunodeficiency. “

Shortly thereafter, an advisory panel to the CDC unanimously voted to recommend a third dose of the COVID-19 vaccine in patients with moderate or severe immunodeficiency. The decision gives patients currently receiving high-dose corticosteroids, alkylants, antimetabolites, TNF inhibitors, and other immunosuppressive biological agents access to a booster dose of the Pfizer BioNTech or Moderna mRNA COVID-19 vaccine.

According to the CDC, the third dose should be given at least 28 days after a second dose of the same vaccine to eligible patients 18 years of age or older for the Moderna vaccine and 12 years or older for the Pfizer BioNTech vaccine.

The American College of Rheumatology followed suit on Aug. 23 with an update to its clinical guidelines for COVID-19 vaccines, recommending a third dose of the mRNA vaccine in patients receiving immunosuppressive or immunomodulatory therapy. These updated ACR recommendations follow CDC guidelines that recommend providers to give the booster at least 28 days after initial treatment.

In particular, the ACR also advises providers to adhere to certain immunomodulatory or immunosuppressive drugs for 1 to 2 weeks after the booster dose, if disease activity permits. Exceptions to this guideline are glucocorticoids and anti-cytokine therapies, including most biological agents. No consensus has been reached on whether to use anti-cytokine drugs such as TNF inhibitors and others, including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists Significantly affect vaccine response to an extent that warrants its temporary interruption.

Operation without data

Several studies have shown that immunocompromised patients do not respond optimally to the COVID-19 vaccination. In an example published by Peter M. Izmirly, MD, from New York University’s Grossman School of Medicine in Arthritis & Rheumatology in early August found that nearly 30% of patients with systemic lupus erythematosus had a low response to the COVID-19 vaccine, with immunosuppressive therapy associated with decreased protection.

Additionally, patients taking certain immunosuppressants such as methotrexate and rituximab (Rituxan, Genentech) have limited response to pneumonia and flu vaccines, according to data.

However, data of any kind on a three-dose vaccine against COVID-19, particularly whether an additional dose would improve a previously lackluster antibody response, is currently limited – although promising.

The results of the first randomized, placebo-controlled study of a third dose of vaccine in transplant recipients – also published in the New England Journal of Medicine in August – showed that an additional dose increased protection.

Data on withholding immunosuppressants when administering a COVID-19 vaccine booster are also limited.

Leonard Calabrese, DO

Leonard Calabrese

“Most clinics are currently recommending boosters that comply with the current guidelines, but whether immunosuppression should be paused is a more controversial topic because – with COVID-19 – there is still no direct data on the effectiveness of such with IMIDs and many societal guidelines differ Provide guidance. ”Kalabrese said. “At our clinic, we recommended that most immunosuppressants be boosted and paused in accordance with updated clinical guidelines from the American College of Rheumatology.”

Take part in the NIH study

About 600 adults from the USA with multiple sclerosis, pemphigus, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis are to take part in the new NIH study entitled “COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders”. Participants must have demonstrated a negative or sub-optimal antibody response to two doses of the Moderna or Pfizer COVID-19 vaccine, or one dose of the Johnson & Johnson vaccine, all received prior to enrollment.

Participants must also receive one of three immunosuppressive therapies: mycophenolate mofetil or mycophenolic acid, methotrexate, or B-cell depleting drugs.

During the study, all participants will receive an additional dose of the same COVID-19 vaccine as they received from their original treatment. However, those taking mycophenolate mofetil, mycophenolic acid, or methotrexate are randomly assigned to either continue their immunosuppressive drugs as they are or to withhold them for a short time before and after the booster.

The primary goal is to determine the proportion of participants who show a significantly better antibody response 4 weeks after the booster vaccination than after the original vaccination.

The study, which is sponsored and funded by the NIH National Institute of Allergy and Infectious Diseases (NIAID), will be followed for 13 months. Preliminary results are expected in November this year, according to the NIH.

Another study, started Aug. 10 by the NIH, will examine antibody responses to a third dose of mRNA vaccine in kidney transplant recipients who failed to respond to two doses of the Moderna or Pfizer series. Preliminary results from this pilot study are expected later this month.

Act now or wait for data?

In response to the start of the new study, Calabrese asked his colleagues a question on Twitter: “Important study evaluating the effects of booster and drug breaks in immunosuppressed people – to ‘answer’ critical questions about the Ab response. Are you going to increase and / or pause your immunosuppressive drugs or wait for the dates? “

In a later conversation with Healio Rheumatology, Calabrese said the current lack of data, combined with the urgent urgency to protect immunocompromised patients from COVID-19, has left rheumatologists a clinical mystery. Should they act now or maybe wait months for the data?

“As this trial starts, will clinicians keep their balance and continue their practice, or will they ‘pause’ and wait for dates to be many months away?” He said. “For my part, I will continue to boost and pause immunosuppressants, as my math is a move to potentially increase vaccine efficacy protection from a wait position where there is no chance for during this critical delta surge that we are an increased immunity. ”Now in. What will you do?”


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COVID-19 and rheumatology

COVID-19 and rheumatology

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