Dupilumab Shows Promise as Bullous Pemphigoid Treatment

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A recent study found that patients with bullous pemphigoid (BP), an autoimmune blistering disease typically affecting elderly individuals, may find itch relief in dupilumab (Dupixent; Sanofi). Researchers stated this could avoid the need for additional immunosuppressive treatments associated with increased morbidity and mortality.¹

Demographics and Treatment Background

All patients in the study (n = 12) had serological and histological confirmation of BP diagnosis prior to treatment initiation. Of those included in the study, 33% were women, the mean age was 76 (± 15 years), and the mean disease duration was 31.5 months (± 19.2 months). Eight of the 12 patients had moderate (Bullous Pemphigoid Disease Area Index (BPDAI) ≥20 to <57) and 4 had mild (BPDAI <20) severity.

Researchers stated that prior treatments included:

The study noted that half of the patients (n = 6) had only received TCS and doxycycline as previous therapy.

Study Methods

Researchers stated that dupilumab was given according to the label in atopic dermatitis, starting with 600 mg subcutaneously (SC) followed by 300 mg SC every 2 weeks. At last follow-up, the study reported that 92% (11/12) of the patients had stopped using TCS and were not on any systemic treatments. Half of the patients (6/12) did not require additional systemic therapy, while researchers stated others used various systemic treatments like PDN and doxycycline. The average duration of TCS use during the study was 1 week, and only one patient used TCS intermittently. Patients were on dupilumab for an average of 4.5 months, and 92% continued the treatment at the final visit.

The study reported that 67% of patients (8/12) achieved complete remission (CR) and 33% (4/12) achieved partial remission (PR) with dupilumab treatment for BP. The mean BPDAI improved “significantly” from baseline to the last follow-up, with a decrease from 24 at baseline to 0 at the final visit. Itch severity, measured by the Worst Itch Numeric Rating Scale (WI-NRS), showed substantial reductions starting from day 1 and continuing through the follow-up period.

Researchers stated that most patients (92%) discontinued all additional systemic and topical treatments and were maintained solely on dupilumab. A strong correlation was observed between reductions in BPDAI and itch severity. No significant differences in itch reduction were found between patients with CR and PR.

Blood tests showed that eosinophil counts normalized in patients with elevated counts at baseline. The study wrote that serum IgE levels remained stable, and variations in autoantibodies against BP180 and BP230 were noted, with some patients showing changes while others remained stable.

Clinically notable cases included:

- Patient 2, who had BP associated with pembrolizumab and was successfully tapered to less frequent dupilumab dosing without relapse.

- Patient 6, who had concurrent psoriasis and achieved remission for both conditions with combined dupilumab and risankizumab treatment.

- Patient 9, who experienced significant improvement in BP and additional symptoms of atopic rhinitis and anosmia with dupilumab.

- Patient 10, who had concurrent atopic dermatitis and saw improvement during dupilumab treatment.

- Patient 12, who initially on dupilumab developed features of epidermolysis bullosa acquisita (EBA), experienced an overlap of BP and EBA, but achieved full remission with an increased dupilumab dose and discontinuation of systemic steroids.

The study reported no significant adverse events.

Conclusion

In this study of dupilumab for treating BP, researchers observed a CR rate of 67% and a PR rate of 33%. A rapid reduction in pruritus was strongly associated with disease improvement as measured by the BPDAI, suggesting that early pruritus reduction could be a predictor of treatment response.

The study suggested that assessing pruritus can provide early insights into treatment efficacy, potentially guiding clinical decisions. Although the study’s findings align with the known effects of dupilumab on pruritus, they underscore the value of early itch reduction in predicting treatment success.² While no significant correlation was observed on days 1 or 3, researchers found a significant correlation was found by day 14.

The study results also highlighted the potential of using early pruritus reduction to identify responders to dupilumab, which could influence treatment strategies, especially in high-risk patients. Given the small sample size and retrospective nature of the study, researchers stated that further research is needed to validate these findings in larger cohorts. Overall, the study found that dupilumab shows promise as a non-immunosuppressive treatment option for BP, potentially improving patient outcomes by enabling earlier identification of effective responders and allowing for the discontinuation of concomitant corticosteroids.

References

1. Thevan J, Schmauch E, Nilsson J, et al. Fast itch relief during dupilumab predicts clinical efficacy in bullous pemphigoid, a retrospective cohort study. Dermatology. Published online July 29, 2024. doi:10.1159/000540590
2. Moghadam P, Tancrede E, Bouaziz JD, et al. Efficacy and safety of dupilumab in bullous pemphigoid: a retrospective multicentric study of 36 patients. Br J Dermatol. 2023;189(2):244-246. doi:10.1093/bjd/ljad136