Efficacy and Safety of Dupilumab in Moderate-to-Severe Bullous Pemphigoid

Abstract

BackgroundBullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.MethodsMedical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).ResultsThe median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22–90 years) and 64.50 years (range: 17–86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1–240 months) and 2.5 months (range: 1–60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1–13 days) and 12 days (range: 5–21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624–2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708–4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100–10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900–14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded.ConclusionsDupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.

Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms

“…Dupilumab, a human IgG4 monoclonal antibody binding the IL4-Rα inhibits IL-4 and IL-13. It is approved in atopic dermatitis and is being studied in BP, and has several reports of treatment success ( 7 , 143 – 145 ). While a phase 2 study of mepolizumab, a humanized IgG1 monoclonal antibody targeting IL-5, was unsuccessful in BP ( 146 ), benralizumab, a human IgG1 monoclonal antibody targeting IL5-Rα that leads to apoptosis of eosinophils and basophils, is being studied.…”

Case Report: Omalizumab Successfully Treated Recalcitrant Bullous Pemphigoid in an Elderly Patient with Multiple Comorbidities

“…In recent years, biologics such as rituximab, omalizumab, and dupilumab have been shown to be effective in BP treatments with a favorable safety profile. [13][14][15] Our patient was recalcitrant to traditional systemic glucocorticoid therapy and had exceedingly high blood glucose levels after treatment. His renal function may have been further impaired if traditional immunosuppressive drugs, such as MTX and cyclosporine A, were used.…”

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

“…In one review, BP from ICB required discontinuation of ICB in 76% of cases ( 46 ). In lieu of continued systemic steroid use or for steroid-refractory cases, rituximab, intravenous immune globulin (IVIg), omalizumab, dapsone, dupilumab, or methotrexate can be considered ( 28 , 47 , 48 ).…”