Efficacy and safety of dupilumab in Chinese patients aged over 60 years with bullous pemphigoid and comorbidities

Dear Editor,

Bullous pemphigoid (BP) is a prevalent autoimmune blistering disorder mediated by autoantibodies, which primarily affects the elderly. Its hallmark clinical manifestations include tense blisters and pruritus.¹ Evidence indicates that Th2 cells play a central role in BP pathogenesis.² Comorbidities often render the elderly, who constitute the majority of BP cases, intolerant to corticosteroids or susceptible to severe side effects, significantly limiting their utility in first-line therapy.^3,4 Dupilumab, an inhibitor targeting IL-4 and IL-13 receptors, key mediators of Th2-driven immune responses, offers a compelling therapeutic alternative.⁵ However, data on the efficacy and safety of dupilumab in elderly Chinese patients with BP remain scarce.

We conducted a single-centre retrospective study at a tertiary hospital in Hangzhou, enrolling patients aged ≥60 years with moderate-to-severe BP and at least one comorbidity. Eligible patients had received systemic corticosteroids for ≥4 weeks but discontinued due to intolerance or severe adverse effects. All patients had ceased corticosteroids for at least two weeks before starting dupilumab and remained off corticosteroids or other biologics during treatment. From January 2023 to January 2024, 77 patients were screened, 48 (62.3%) met the criteria, and all completed ≥32 weeks of follow-up. Baseline characteristics have been summarised in Table 1.

The primary endpoints were bullous pemphigoid disease area index (BPDAI) and numerical rating scale (NRS) score changes at weeks 16 and 32, respectively. Dupilumab significantly reduced both scores, with median BPDAI decreasing from 67 (60.3-73.5) at baseline to 3 (2-5) at 16 weeks and 1 (0-3) at 32 weeks (both P<0.01), demonstrating strong efficacy [Figure 1]. Pruritus severity, linked to baseline comorbidities, improved significantly post-treatment. Median NRS dropped from 8 (7-9) to 0 (0-0) at 16 weeks (P<0.01), highlighting symptom relief, accompanied by visible clinical resolution of lesions [Figure 2 a-d]. Concurrently, median serum levels of anti-BP180 and anti-BP230 antibodies had declined significantly by week 16, from 222.0 (92.5–366.8) and 11.5 (3.0–96.0) RU/mL at baseline to 49 (11.3–111.8) and 4 (2.0–18.3) RU/mL, respectively (P<0.01), further supporting the therapeutic effectiveness of dupilumab [Figure 1]. Remarkably, no patients experienced disease recurrence after corticosteroid withdrawal, affirming the ability of dupilumab to sustain disease control independently.

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Figure 1:

Changes in clinical indicators after administration of dupilumab. (BPDAI: Bullous pemphigoid disease area index, NRS: Numerical rating scale)

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Figure 2a:

Extensive blisters and erythema on the trunk before treatment in patient 1.

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Figure 2b:

Resolution of blisters and erythema with dupilumab at week 4 in patient 1.

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Figure 2c:

Patient 2: Multiple blisters and erythematous plaques on the lower limbs before treatment in patient 2.

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Figure 2d:

Significant regression of blisters and erythema with dupilumab treatment at week 4.

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In the safety analysis of the 48 elderly Chinese patients, five experienced transient, asymptomatic eosinophilia, which resolved spontaneously. Some reported adverse events included injection site reactions (6.3%), arthralgia (4.2%), and skin erythema (8.3%). Notably, no ocular complications, including conjunctivitis, were observed. No serious adverse events occurred throughout treatment or follow-up, underscoring the favourable safety profile of dupilumab in this cohort.

Our study included 10 (20.8%) patients with diabetes, 16 (33.3%) with hypertension, 7 (14.6%) with malignant tumours, and 8 (16.7%) with cardiovascular or cerebrovascular diseases. No significant changes were observed in these pre-existing conditions during treatment, nor did any of them progress or metastasise. These findings indicate that dupilumab is an effective and appropriate treatment option for elderly BP patients with comorbidities.

In conclusion, our study demonstrates that dupilumab is both safe and effective for BP patients aged 60 and older with comorbidities. The presence of comorbid conditions neither compromises efficacy nor the safety of the drug. Moreover, its use minimises the intolerance and adverse effects commonly associated with high-dose corticosteroids in this population. Thus, dupilumab emerges as a promising first-line therapy for elderly patients with comorbidities. Nevertheless, further studies are needed to establish its long-term efficacy and safety.