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

Abstract

Background: Bullous 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.

Methods: Medical 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).

Results: The 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.

Conclusions: Dupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.

Keywords: IL-4/IL-13; bullous pemphigoid; corticosteroid-spare; dupilumab; pruritus.

Figure 1

Algorithm describing the distribution, the treatments, and taper schedule received by the patients with moderate-to-severe BP.

Figure 2

Primary outcomes in the dupilumab group compared with the conventional group. (A) Time to stop new blister formation (p = 0.028 by Kaplan-Meier analysis). (B) Time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) (p = 0.0053 by Kaplan-Meier analysis). (C) Hospitalization duration (p > 0.05 by Kaplan-Meier analysis). The numbers in green and red represent the median number of days for the dupilumab group and conventional group, respectively. (D) The total amount of methylprednisolone administered to patients in the dupilumab group and conventional group (at the time of reaching the minimal dose) (p = 0.036 by Mann-Whitney U test) (^* p < 0.05; ^** p < 0.01; ns, not significant).

Figure 3

Comparison of NRS score between two treatment groups. NRS score has decreased to varying degrees from weeks 0 to 2 in the dupilumab group (A) (^*** p < 0.001 by Mann-Whitney U test), and the conventional group (B) (^*** p < 0.001 by Mann-Whitney U test). (C) Patients in dupilumab group showed more privileges in relieving itch (p = 0.034 by two-way RM ANOVA).

Figure 4

Comparison of single BPDAI (skin: erosions/blisters) score between two treatment groups. BPDAI score has declined to varying degrees from weeks 0 to 2 in the dupilumab group (A) (^*** p < 0.001 by Mann-Whitney U test) and the conventional group (B) (^*** p < 0.001 by Mann-Whitney U test). (C) BPDAI score decreased more rapidly in patients in the dupilumab group than the conventional group (p= 0.0308 by two-way RM ANOVA).

Figure 5

Comparison of EOS% between two treatment groups. EOS% has decreased to varying degrees from weeks 0 to 2 in the dupilumab group (A) (ns, not significance; p > 0.05 by Mann-Whitney U test) and the conventional group (B) (ns, not significance; p > 0.05 by Mann-Whitney U test). (C) Comparison of improvement in EOS% in both groups (p > 0.05 by two-way RM ANOVA).

Figure 6

Comparison of IgE between two treatment groups. IgE has decreased to varying degrees from weeks 0 to 2 in the dupilumab group (A) (ns, not significant; p > 0.05 by Mann-Whitney U test) and the conventional group (B) (ns, not significant p > 0.05 by Mann-Whitney U test). (C) Comparison of improvement in IgE in both groups (p > 0.05 by two-way RM ANOVA).

Figure 7

Clinical photographs of one patient with BP who received dupilumab in combination with conventional therapy. Admission (A); 2 weeks after dupilumab (600 mg) treatment (B).