Dupilumab Associated With Improved Outcomes in Bullous Pemphigoid

Patients with bullous pemphigoid treated with dupilumab saw symptom improvement at 4 weeks after treatment initiation, according to study results published in JAMA Dermatology.

A known factor in the pathogenesis of bullous pemphigoid is inflammation of T_H2. Dupilumab blocks IL-4Rα to downregulate a T_H2-related signal pathway, making it a potential novel therapy for bullous pemphigoid.

Researchers conducted a retrospective cohort study at 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China from January 2021 to July 2022. They evaluated the efficacy, safety, and prognostic risk factors of dupilumab for adult patients with bullous pemphigoid.

Eligible patients had been diagnosed with bullous pemphigoid based on guideline indicators and were followed for 4 weeks or longer after dupilumab initiation. Dupilumab was administered at an initial dose of 600 mg followed by a300-mg dose every 2 weeks. The primary outcome was the proportion of patients who achieved disease control within 4 weeks, with disease control defined as cessation of new lesions or pruritus and healing of existing lesions.

The analysis included 146 patients with bullous pemphigoid. Median age of patients was 73 years (interquartile range [IQR], 64-85 years) and 58.9% were men. The median duration of follow-up was 24.6 weeks (IQR, 11.5-38.4 weeks).

Disease control was achieved by 127 (87.0%) patients within 4 weeks of treatment initiation, and in 109 patients (74.7%) within 2 weeks of treatment initiation. Median time to disease control was 14 days (IQR, 7-14).

A total of 52 patients (35.6%) achieved complete remission during the observation period. Rates of complete remission rates at weeks 16, 32, 48, and 64 were 41.5% (39 of 94 patients), 52.6% (30 of 57 patients), 57.9% (11 of 19 patients), and 62.5% (5 of 8 patients), respectively. Among the 52 patients achieving complete remission, 21 (40.4%) received treatment with oral steroids.

Relapse occurred in 13 of 146 (8.9%) patients at a median of 14.0 weeks (IQR, 5.0-28.7). Cumulative relapse rates at weeks 16, 32, 48, and 64 were 6.6%, 9.5%, 17.1%, and 30.9%, respectively.

During the observation period, dupilumab was discontinued by 78 patients (53.4%), of whom 50 (64.1%) discontinued due to well-controlled symptoms. The researchers noted that relapse rates were lowest among patients who maintained the initial treatment regimen after 16 weeks and highest among those who had discontinued dupilumab by 16 weeks. They suggested that treatment maintenance or interval-prolonged treatment may be a better option than discontinuation.

Median bullous pemphigoid Disease Area Index and itching Numerical Rating Scale scores were reduced rapidly — from 85 (IQR, 48-120) and 7 (IQR, 5-8), respectively, at baseline to 18 (IQR, 9-32) and 0 (IQR, 0-2), respectively, during the second week of therapy — and remained low throughout the study (both P <.001). By week 16, median levels of serum anti-BP180 and anti-BP230 antibodies had decreased significantly.

Adverse events (AEs) were reported in 39 patients (26.7%); most AEs were mild and did not lead to treatment discontinuation. Skin and soft tissue infections were the most common AEs (9.6%), especially in patients taking concomitant oral steroids. Eosinophilia was also common, occurring in 9 (6.2%) patients.

In multivariate logistic regression analysis, a serum anti-BP180 antibody level greater than 50 RU/mL was the only positive factor associated with 4-week disease control (odds ratio, 3.63; 95% CI, 0.97-12.61; P =.045). Among the patients, men were more likely to experience relapse (hazard ratio, 10.97; 95% CI, 1.42-84.92; P =.02).

Limitations of this study include the lack of restrictions on concomitant medications and relatively small numbers of patients assigned to each treatment regimen, which could have led to bias.

“In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP,” the researchers concluded. They cautioned that, while the safety profile was favorable, “concurrent infection and eosinophilia might pose potential concerns.”