Dupilumab confers benefit in bullous pemphigoid

The monoclonal antibody dupilumab, alone or in combination with conventional agents, appeared to effectively control bullous pemphigoid (BP), a study from China has shown.

“Dupilumab effectively and rapidly treated BP by inhibiting activities of multiple cell types,” reported Tianmeng Yan from The University of Hong Kong Shenzhen Hospital, Shenzhen, Guangdong, China, at WCD 2023.

At week 4, similar proportions of participants in both study groups achieved complete response (CR*) and partial response (PR*). In the dupilumab group, 12 patients had a CR and eight had a PR. Of note, half (n=6 and 4 [CR and PR]) of these patients were on dupilumab monotherapy. The corresponding numbers in the corticosteroid group were 10 for both CR and PR. A between-group comparison did not yield a significant difference (p=0.75). [WCD 2023, session LB02; Front Immunol 2023;doi.org/10.3389/fimmu.2023.1194088]

Safety-wise, there was an obvious difference in the cumulative dose between the dupilumab and conventional groups during the first 4 weeks (200 vs 800 mg; p<0.001). A total of 26 adverse events (AEs) were reported with conventional treatment at week 24, whereas with dupilumab, there were only six. Moreover, most AEs with dupilumab were grade 1–2, while a number of AEs in the conventional group were grade 3 in severity (eg, ophthalmopathy, electrolyte disturbance, hepatic impairment, diabetes).

Dupilumab treatment also led to a reduction in the percentage of eosinophils (p<0.01), but not anti-BP180 IgG (p=0.66). “[This implies that] BP180 antibody may not reflect the disease activity of BP patients treated with dupilumab,” Yan explained.

Plasma samples were collected from three dupilumab recipients pre- and post-treatment. In the plasma proteomic analysis, 879 proteins were discovered. Paired T test revealed upregulation of four proteins and downregulation of 26 proteins.

Among the differentially expressed, downregulated proteins following dupilumab use were immune system proteins – CR2 (p=0.03), S100A12 (p=0.01), PRG2 (p=0.013), and ICOSL** (p=0.025). These proteins are involved in the activation of complement (CR2), mast cells (S100A12), and eosinophils (PRG2), Yan said.

The ICOSL reduction post-dupilumab treatment was further validated by ELISA test (p=0.034). “ICOSL is important in the interaction between T and B cells,” Yan said. TARC*** also decreased after dupilumab treatment (p=0.016).

Pharmacological option for BP

BP is a chronic autoimmune disease characterized by erythema, skin blisters, and severe itching, as well as subepidermal blister formation with eosinophil infiltration. Moderate-to-severe BP are usually treated with corticosteroids and immunosuppresants, but their use is limited by severe AEs.

Yan and colleagues retrospectively evaluated 40 patients who have received dupilumab or conventional agents (n=20 in each group). More than half were male and mean age overall was 70.55 years. Disease duration was 10.10 months. In 22 patients, eosinophils were not within normal range. Eighteen participants were treated for recurrence; the rest were on initial treatment.

Half of the dupilumab cohort also received corticosteroids (prednisolone 2.5–100 mg). Following a loading dose of 600 mg, dupilumab was given at a dose of 300 mg every 1–4 weeks on four to 10 occasions. In the conventional group, prednisolone was initially given at a dose of 0.2–1 mg/kg; this was reduced 1 or 8 weeks after disease control.

“Overall, dupilumab rapidly treats BP as do conventional drugs by inhibiting the activities of many types of immune cells, regulating the interactions between T and B cells, and inhibiting eosinophil, mast cell, and complement activation,” Yan said. “Dupilumab may be a new option for BP.”

Yan added that ICOSL and TARC could be new clinical biomarkers for BP. Further investigation in larger cohorts are warranted to validate these data.