Panel OKs vaccination during dupilumab treatment
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Key takeaways:
- Dupilumab’s package insert advises completion of all vaccinations before beginning treatment.
- A review of nine studies found no associations between dupilumab and decreased antibody response.
Vaccinations can be safe and effective during dupilumab treatment, according to the consensus of a panel published in Annals of Allergy, Asthma & Immunology.
But these vaccinations should proceed only after physicians and patients have shared in the decision-making, Jay A. Lieberman, MD, associate professor, department of pediatrics, University of Tennessee Health Science Center, and colleagues wrote.
Dupilumab (Dupixent; Regeneron, Sanofi) has been approved for treating a variety of inflammatory diseases, the authors wrote, yet patients in its phase 3 trials were not allowed to receive live vaccinations during treatment.
“The truth is that any potential effects were theoretical and not based in any empirical evidence,” Lieberman, who also is a member of Healio’s Allergy and Asthma Peer Perspective Board, told Healio.
“Possible, theoretical effects could be that patients would mount a poor response to the vaccine or that patients would be susceptible to acquiring infection from a live vaccine,” he continued.
This lack of live vaccinations during dupilumab’s trials has led to a lack of efficacy and safety data about the biologic’s effects on vaccination, the authors continued.
Further, the authors said, dupilumab’s current package insert advises patients to complete all age-appropriate vaccinations before beginning treatment since the drug’s impact on vaccines is unknown.
“The main clinical trials of dupilumab did not allow for vaccination. Due to this, the package insert recommended not giving these vaccinations to patients on dupilumab. Thus, no one wanted to take any risk,” Lieberman said.
But once dupilumab was approved for children at age 6 months, this lack of data became a bigger clinical issue, and the need for studies and evidence-based guidance became evident, he continued.
“For example, MMR is an attenuated (weakened) live virus vaccine,” Liberman said.
MMR vaccines are recommended for children aged 12 to 15 months, with a second dose between ages 4 and 6 years.
“Any child on dupilumab treatment would face a clinical question of risks/benefits of dupilumab or getting MMR,” Lieberman said.
Literature review
A search of 10 databases from inception through January 2022 yielded nine studies that described the vaccination of human beings of any age who also were receiving dupilumab.
These studies included five cohort studies, one randomized controlled trial, two retrospective case-control studies and one case series. Half were conducted in the United States, the authors added.
Six included patients with atopic dermatitis, two included patients with asthma and one included patients who had both AD and asthma. Participants ranged from age 8 months to age 64 years.
Also, seven studies assessed how dupilumab impacted COVID-19 vaccination, primarily with mRNA vaccines. One investigated protein and polysaccharide vaccines. Two examined the administration of live vaccines among patients who used dupilumab.
“Probably the most noteworthy finding was that when live vaccines were given accidentally or on purpose to patients who were receiving dupilumab, there were no safety concerns, and no patients developed infection with the virus that they were vaccinated against,” Lieberman said.
Although there were no prospective randomized controlled trials or controlled prospective trials that evaluated these outcomes as primary endpoints, Lieberman called the evidence noteworthy.
“While the numbers are small, this is very reassuring,” Lieberman said. “Dupilumab probably does not make patients susceptible to infection from a live viral vaccine.”
Based on antibody titer increases or overall titers, one randomized controlled study found similar immune responses between dupilumab and placebo groups to tetanus (83.3% vs 83.7%) and meningococcal polysaccharide (86.7% vs 87%) 16 weeks after vaccination.
The patients in the dupilumab group also were less likely to develop Tdap-IgE (34.8%) than the placebo group (62.2%) by week 32, indicating the biologic’s impact on total IgE production, the authors said.
Among studies that examined COVID-19 vaccinations during dupilumab treatment, one found reduced titers after vaccination, but the others did not find differences in titers between patients who were on an anti-IL4 or anti-IL13 therapy and those who were not after vaccination.
In a prospective observational study, patients on biologic therapies had significantly lower antibody levels between 25 and 49 days after receiving either brand of the mRNA COVID-19 vaccines.
These levels totaled approximately 67% of the levels among the patients in the control group, with similar results for other SARS-CoV-2 antigen, the authors said, although the clinical relevance of this decrease is not known.
The other studies in the review did not report any differences in antibody response between patients who were using dupilumab and patients in their control groups.
These overall results indicate that the risk for impaired humoral immune responses among patients on dupilumab who receive non-live vaccines is low, although the authors said the small number of patients studied and the shorter study times may bias these conclusions, with longer study intervals possibly diminishing these responses.
Panel review
The authors sent a narrative summary of this review to a panel of 28 specialists with track records in allergy and health policy as well as expertise in adverse reactions and immune responses to vaccines, along with specialty training in cytokine biology.
These experts also were asked to say whether they agreed with three statements, using a five-point scale with a score of 1 indicating strong disagreement and a score of 5 indicating strong agreement. These statements included:
- It is safe to administer live vaccines to patients receiving dupilumab.
- Patients mount appropriate antibody response to vaccines while on dupilumab.
- I would recommend giving live vaccines to patients on dupilumab after a shared decision-making discussion with the patient and/or their family.
The authors defined consensus for these statements as agreement or disagreement of 75% or higher. Results included 89.3% agreement on the first statement, 92.9% agreement on the second statement, and 89.3% agreement with 3.6% disagreement (n = 1) on the third statement. Lieberman called these results surprising.
“We were hoping for around 80% consensus,” he said. “But I think this goes to show that the vast majority of clinicians who understand how dupilumab works were in agreement that this is safe.”
Members of the panel also could provide free text responses, where they noted the limited data available, a lack of any theoretical reason why treatment would impact vaccination and their own experience in treating patients with dupilumab, among other comments.
“It was noteworthy how many experts were excited to see this project being done, because they felt the same way and were hoping to get this accomplished,” Lieberman said.
These responses indicate that the members of the panel shared a high level of consensus that vaccination during dupilumab treatment is safe, that the immune response would be robust, and that they would recommend this course to patients after engaging in shared decision-making, the authors said.
Specifically, the authors noted the importance of considering the harms of discontinuing dupilumab to commence vaccination, or of delaying vaccination to implement dupilumab treatment, during shared decision-making with patients.
“My hope is that we see increased use of live vaccines in patients receiving dupilumab and hopefully develop some real-world data to prove, one way or another, the response patients have to these vaccines,” Lieberman said.
Reference:
- New ACAAI position paper examines safety of receiving live vaccines while on dupilumab. https://www.eurekalert.org/news-releases/1047915. Published June 11, 2024. Accessed June 11, 2024.
For more information:
Jay A. Lieberman, MD, can be reached at jlieber1@uthsc.edu.
Perspective
Back to Top
Although derived from studies with a small number of subjects, the conclusion by experts that vaccines are effective while on treatment with dupilumab and that live vaccines are likely safe is an important clinical recommendation.
With dupilumab being used in progressively lower age groups for a variety of indications that themselves are associated with high morbidity, no disseminated infections were reported post-vaccination. Dupilumab is not an immunosuppressive agent, and, therefore, this safety signal is important to document and report.
Young children and adolescents are the ones most likely to require live vaccines without alternative options in some cases. This review provides reassurance that doctors can prescribe these vaccines in individuals on dupilumab therapy without a high level of concern for safety and efficacy. There is no need to interrupt biologic therapy for the purpose of immunization.
As biologics continue to be used, periodic retrospective reviews of vaccine efficacy and safety data should be undertaken.
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