Dupilumab for the Treatment of Recalcitrant Bullous Pemphigoid

Kaye, Alex; Gordon, Samantha; Deverapalli, Sandhya; Her, Min Ji; Rosmarin, David

doi:10.1001/jamadermatol.2018.2526

Cited by 81 publications

(76 citation statements)

References 6 publications

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“…Dupilumab may be considered as a prospective treatment option for IL-4 and IL-13-related allergic diseases, such as asthma. Furthermore, some curative effects were reported for bullous pemphigoid and alopecia areata (6,7). To the best of our knowledge, this is the first case of MF becoming apparent in a patient with AD who was treated with dupilumab.…”

Section: Discussionmentioning

confidence: 77%

Diagnosis of Mycosis Fungoides Following Administration of Dupilumab for Misdiagnosed Atopic Dermatitis

Chiba¹,

Nagai²,

Osada³

et al. 2019

Acta Derm Venerol

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The effect of anti-interleukin (IL)-4/-13 treatment, dupilumab, on allergic diseases and the resulting various unexpected phenomena have been reported in the literature. The clinical features of mycosis fungoides (MF) with multiple erythematous lesions are similar to those of atopic dermatitis (AD). Thus, anti-IL-4/-13 therapy may be erroneously administered to patients with MF with features similar to those of AD. This report is the first to describe a case of MF diagnosed after administration of dupilumab for AD. CASE REPORTA 58-year-old man had had AD since early childhood. Although remission had occurred in adolescence, eczema had appeared on his trunk and limbs at the age of 47 years. He presented to a dermatologist and was administered topical corticosteroid ointment, betamethasone butyrate propionate, based on the diagnosis of recurrent AD. In 2013 the patient was referred to our university for treatment of a carcinoma of the maxillary sinus using chemoradiotherapy. Treatment was successful. Subsequently, the patient continued treatment for AD in our department. The cutaneous eruption was somewhat controlled by topical treatments; however, at times he experienced intense itching ( Fig. 1). He reported a history of allergic rhinitis, conjunctivitis and asthma. Given the severity of his AD, treatment with dupilumab 600 mg, subcutaneously was initiated on the first day, followed by 300 mg every 2 weeks in 2018. Serum examination prior to administration revealed elevated levels of thymus-and activation-regulated chemokine (TARC, 4,634 pg/ ml; normal range: < 450 pg/ml), IgE (1,280 IU/ml; normal range: < 250 IU/ml), and lactate dehydrogenase (LDH, 269 U/l; normal range: 124-224 U/l). The eosinophil count was within normal limits. The Eczema Area and Severity Index (EASI) was 34.4, while the Dermatology Life Quality Index (DLQI) was 8. During treatment with dupilumab, the faint erythematous lesions on the face and trunk became more obvious, despite continuous application of the topical steroid (Fig. 2). After 1 month, the EASI and DLQI were slightly decreased (29 and 6, respectively); however, there was no improvement in pruritic symptoms. Laboratory tests revealed that TARC, IgE, and LDH levels were 3,948 pg/ml, 924 IU/ml, and 287 U/l, respectively. Owing to exacerbation of the erythematous lesions, skin biopsy of the erythematous macule on the trunk was performed. Histopathology showed band-like atypical lymphocytic infiltration into the dermis. Atypical epidermotropic lymphocytes without spongiosis were observed in the epidermis, which formed Pautrier's microabscess (Fig. 3). Fig. 1. (a) Erythematous lesions on the face. (b) Poikiloderma lesions accompanied by papules and nodules on the back. Written permission from the patient is given to publish these photos. Fig. 2. (a) Face and (b) back after 1 month of treatment with dupilumab.Written permission from the patient is given to publish these photos. Fig. 3. Histopathology of the biopsy specimen from the erythematous lesion on the chest shows lymphocytic infi...

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Section: Discussionmentioning

confidence: 77%

Diagnosis of Mycosis Fungoides Following Administration of Dupilumab for Misdiagnosed Atopic Dermatitis

Chiba¹,

Nagai²,

Osada³

et al. 2019

Acta Derm Venerol

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“…After 3 months of therapy, the patient had clinical and serological resolution, and no lesions were detected at 10 months while on dupilumab monotherapy (Kaye et al, 2018). Actually, a successful treatment of a single patient with severe BP and treatment limitation using dupilumab has already been reported.…”

Section: Bullous Pemphigoidmentioning

confidence: 96%

“…Actually, a successful treatment of a single patient with severe BP and treatment limitation using dupilumab has already been reported. After 3 months of therapy, the patient had clinical and serological resolution, and no lesions were detected at 10 months while on dupilumab monotherapy (Kaye et al, 2018).…”

Section: Bullous Pemphigoidmentioning

confidence: 97%

“…In fact, BP patients show a predominant type-2 response, suggesting that Th2 cells are primary involved in the loss of tolerance against BP180 (Cozzani et al, 2018;Maglie & Hertl, 2019). Eosinophils may be involved in the maintenance of a Th2-type response, via the production of IL-4, IL-5, and IL-13 (Cozzani et al, 2018;Giomi, Caproni, Calzolari, Bianchi, & Fabbri, 2002;Gounni Abdelilah et al, 2006;Kaye, Gordon, Deverapalli, Her, & Rosmarin, 2018;Maglie & Hertl, 2019). Autoreactive Th2 cells are thought to exert a dual role in BP: they stimulate proliferation and autoantibody production by B-cells via CD40-CD40L interaction and contribute to eosinophil recruitment and activation.…”

Section: Bullous Pemphigoidmentioning

confidence: 99%

“…Autoreactive Th2 cells are thought to exert a dual role in BP: they stimulate proliferation and autoantibody production by B-cells via CD40-CD40L interaction and contribute to eosinophil recruitment and activation. Eosinophils may be involved in the maintenance of a Th2-type response, via the production of IL-4, IL-5, and IL-13 (Cozzani et al, 2018;Giomi, Caproni, Calzolari, Bianchi, & Fabbri, 2002;Gounni Abdelilah et al, 2006;Kaye, Gordon, Deverapalli, Her, & Rosmarin, 2018;Maglie & Hertl, 2019). Furthermore, Büdinger et al (1998) demonstrated a type-2 response to BP180 in BP patients, in opposition to MHCII restricted controls who mounted a type-1 response without disease.…”

Section: Bullous Pemphigoidmentioning

confidence: 99%

See 2 more Smart Citations

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Russo

Cozzani

Gasparini

et al. 2020

Dermatologic Therapy

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Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases. K E Y W O R D Sblistering diseases, bullous pemphigoid, dupilumab, mucous membrane pemphigoid, pemphigus vulgaris

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Evaluation of Dupilumab in Patients With Bullous Pemphigoid

Zhao,

Wang,

Liang

et al. 2023

JAMA Dermatol

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ImportanceDupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study.ObjectiveTo assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes.Design, Setting, and ParticipantsA retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded.Main Outcomes and MeasuresThe primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed.ResultsAmong 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02).Conclusions and RelevanceIn this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

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Dupilumab for the Treatment of Recalcitrant Bullous Pemphigoid

Cited by 81 publications

References 6 publications

Diagnosis of Mycosis Fungoides Following Administration of Dupilumab for Misdiagnosed Atopic Dermatitis

Diagnosis of Mycosis Fungoides Following Administration of Dupilumab for Misdiagnosed Atopic Dermatitis

Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases?

Evaluation of Dupilumab in Patients With Bullous Pemphigoid

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