Recommendations for Vaccination in Children with Atopic Dermatitis Treated with Dupilumab: A Consensus Meeting, 2020

Abstract

Dupilumab is the only biologic therapy currently approved in Europe and the United States for severe atopic dermatitis in patients 6 years of age or older. Off-label use is rationalized in younger children with severe atopic dermatitis. Decisions about vaccination for children on dupilumab are complex and depend on both the child's current treatment and the type of vaccination required. To achieve consensus on recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab, a review of the literature and a modified-Delphi process was conducted by a working group of 5 panelists with expertise in dermatology, immunology, infectious diseases and vaccination. Here, we provide seven recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab. These recommendations serve to guide physicians' decisions about vaccination in children with atopic dermatitis treated with dupilumab. Furthermore, we highlight an unmet need for research to determine how significantly dupilumab affects cellular and humoral immune responses to vaccination with live attenuated and inactivated vaccines.

Fig. 1

Vaccine response and the potential impact of dupilumab. Dupilumab is a human (IgG4) monoclonal antibody anti-IL-4 receptor that blocks the α-subunit shared by IL‐4R receptor type I and II, decreasing the signal induced by IL-4 and IL-13. a T cell-dependent response vaccines generate humoral and cellular responses with immune memory. After recognition of the antigen, APCs (B cells, macrophages, or DCs) present the processed antigen to naive T cells via peptide-MHC II. Co-stimulation between B7 ligands (CD80/CD86) and CD28 on the T cell is required. The type of pathogen determines the cytokine environment, which dictates the development of a specific T cell phenotype. IL-12, secreted by the DC in response to virus infection or intracellular bacteria, promotes polarization towards the T_H1 pathway, which secretes IFNγ and activates CD8 + CTLs and phagocytic cells and inhibits T_H2 development. In contrast, IL-4 initiates polarization to T_H2 pathways and inhibits T_H1 development. Via activation of STAT6 and GATA3, IL-4 promotes gene expression of IL‐4, IL‐5, and IL‐13. APCs trigger a T_H2 cell response in the presence of thymic stromal lymphopoietin, IL-25, and IL-33 produced by epithelial cells. T_H2 responses drive B cell activation, requiring co‐stimulatory signals through the CD40–CD40L (CD154) from the T_H cell and leading to differentiation into a plasma cell, isotype class switching, antibody secretion and clonal expansion of memory B cells. IL-4 acts as a B cell growth factor, and IL-6 assists in maturation of the antibody response. Theoretically, blocking IL-4 does not impair response to viral infection. b Polysaccharide vaccines elicit a T cell–independent response. The antigen directly interacts with B cells, producing antibodies limited to IgM without immunologic memory. Live bacteria: BCG. Live virus: influenza (intranasal), measles, mumps, oral polio, rotavirus, rubella, varicella zoster, yellow fever. Killed virus: inactivated poliovirus. PS conjugated: Haemophilus influenzae type B, meningococcal and pneumococcal conjugated. Protein: acellular pertussis, diphtheria, hepatitis B, human papillomavirus, influenza, tetanus. Ab antibody, aB cell activated B cell, Ag antigen, APC antigen presentation cell, BCG bacille Calmette-Guerin, BCR B cell receptor, CTL cytotoxic T lymphocytes, DC dendritic cell, IFN interferon, Ig immunoglobulin, IL interleukin, m B cell memory B cell, m CD8 + T cell memory T cell, mDC mature dendritic cell, MHC major histocompatibility complex, PS polysaccharide, T_H T helper, TNF tumor necrosis factor, TCR T cell receptor, TGF transforming growth factor. Created with BioRender.com