Anti-interleukin 4 receptor α antibody for the treatment of Chinese bullous pemphigoid patients with diverse comorbidities and a 1-year follow-up: a monocentric real-world study

Abstract

Background: Bullous pemphigoid (BP) is a common subepidermal bullous disorder that lacks adequate treatment alternatives. Dupilumab, an anti-interleukin (IL) 4 receptor α antibody blocking Th2 molecules IL-4 and 13, has been used off-label and shown to be effective in refractory BP cases.

Methods: BP patients with various disease severities and comorbidities were included in this case series. All patients received dupilumab alone or in combination with immunosuppressants in a real-world setting. Complete remission (CR) was defined as the absence of pruritus symptoms and previous BP eruptions, with only hyperpigmentation patches and without newly occurring lesions for at least 4 weeks. Disease relapse was classified as the appearance of three or more new lesions within 1 month or at least one large urticarial or eczematous lesion that did not resolve within a week.

Findings: Ten individuals were enrolled in this case series. Pruritus symptoms and BP eruptions improved significantly in nine patients (90%). Seven patients (70%) attained CR, including all mild-to-moderate (100%) cases and three of six (50%) severe BP cases. At the dupilumab monotherapy stage, eosinophilia was observed in two severe cases. One patient out of seven (14.3%) relapsed after 1 year of follow-up after CR.

Conclusion: Treatment of BP with diverse comorbidities with anti-IL-4 receptor α antibody provides further credentials to a prospective randomized study. More impressive efficacy and safety profiles were observed in patients with mild-to-moderate disease after 1 year of follow-up. Eosinophilia may occur in patients receiving dupilumab monotherapy.

Keywords: Bullous pemphigoid; biologics; comorbidity; dupilumab; immunosuppressant; real-world study; severity.

Figure 1

Clinical presentation before and after therapy in case 1. Erythematous patches and tense bullae appear on the trunk, extremities, and hands before treatment (A–C). Bullae and crusting disappeared with hyperpigmentation (D–F) after 14 weeks of treatment with dupilumab combined with immunosuppressive therapy.

Figure 2

The pathogenesis and emerging therapeutic strategies in bullous pemphigoid. The existence of IgG antibodies and the complement element C3, which attacks the BMZ, characterizes BP. Immune complex production triggers the activation of complement, which results in the migration of eosinophils, mast cells, and neutrophils, as well as the secretion of proteases and inflammatory markers, thereby inducing dermal-epidermal split. The pattern of distribution of the subsets of T cells is atypical. The Th2, Tfh, and Th17 groupings are elevated, whereas the Treg cell count is diminished. By means of the release of IL-17, aberrant Th17 cell types enhance the pro-inflammatory immune reaction, stimulate neutrophils, magnify the inflammatory process, and promote tissue injury. Th2 cells and Th2 cell-released IL-4 stimulates B cell growth, antibody synthesis, and class-switching of immunoglobulins. The improper functioning of Treg cells promotes the activation of autoreactive CD4+ T lymphocytes and the creation of autoantibodies. Enhanced Tfh proliferation facilitates the production of autoantibodies in BP by B cells. Possible targets range from CD20+ lymphocytes with rituximab to the Th2 axis with dupilumab, and omalizumab or the IL-17/IL-23 axis, as well as the inhibition of particular complement or inflammatory mediators.