Dupilumab effectively and rapidly treats bullous pemphigoid by inhibiting the activities of multiple cell types

Tianmeng Yan; Yinghan Xie; Yuhua Liu; Ying Shan; Xiaoyan Wu; Jing Wang; Ya-Gang Zuo; Zhenying Zhang

doi:10.3389/fimmu.2023.1194088

Dupilumab effectively and rapidly treats bullous pemphigoid by inhibiting the activities of multiple cell types

Front Immunol. 2023 Jul 27:14:1194088. doi: 10.3389/fimmu.2023.1194088. eCollection 2023.

Authors

Tianmeng Yan^{1

2}, Yinghan Xie³, Yuhua Liu², Ying Shan³, Xiaoyan Wu², Jing Wang⁴, Ya-Gang Zuo³, Zhenying Zhang^{1

4}

Affiliations

¹ Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² Department of Dermatology, The University of Hong Kong Shenzhen Hospital, Shenzhen, China.
³ Department of Dermatology, Peking Union Medical College Hospital, Beijing, China.
⁴ Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.

Abstract

Background: Bullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients.

Objective: We evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth.

Methods and results: A multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment.

Conclusion: Dupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.

Keywords: ICOSL; TARC; bullous pemphigoid; dupilumab; eosinophil.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Autoimmune Diseases*
Humans
Pemphigoid, Bullous*
Proteomics
Retrospective Studies

Substances

dupilumab
Adrenal Cortex Hormones

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant number 81972944), National High Level Hospital Clinical Research Funding (2022-PUMCH-B-092) and Beijing Municipal Natural Science Foundation (7232118).