Corticosteroid-Sparing Control of Bullous Pemphigoid with Dupilumab and Tripterygium Glycosides: A Real-World Cohort with Longitudinal Transcriptomics.

BACKGROUND

Bullous pemphigoid (BP) often requires long-term corticosteroids with substantial adverse effects. Effective corticosteroid-sparing treatments could improve safety and quality of life for patients with BP.

OBJECTIVE

To evaluate the clinical efficacy, safety, and transcriptomic correlates of dupilumab combined with tripterygium glycoside (TG) in moderate-to-severe BP.

MATERIALS AND

METHODS

We conducted a clinical cohort study at Peking Union Medical College Hospital. Twelve consecutive BP patients (bullous pemphigoid disease area index [BPDAI] ≥20) who had received dupilumab combined with oral TG were retrospectively identified. Systemic corticosteroids were avoided whenever feasible; rescue initiation or dose escalation was permitted for relapse or inadequate control. Outcomes included BPDAI, pruritus Numeric Rating Scale (NRS), serum anti-BP180 antibody levels, and eosinophil percentage from baseline to week 12. Safety was monitored throughout follow-up. Longitudinal peripheral blood samples were collected before and after treatment for transcriptomic profiling.

RESULTS

Among 12 patients, 10 (83%) achieved complete remission within 3 months, including 9 (75%) without initiating systemic corticosteroids or dose escalation. Median time to disease control was 8 days (IQR, 7-9.75). Significant improvements were observed in BPDAI (-37.50; 95% CI, -62.65 to -30.65; p = 0.003), pruritus NRS (-7.58; 95% CI, -9.00 to -6.00; p = 0.002), anti-BP180 antibody (-33.00 U/mL; 95% CI, -62.00 to -7.00; p = 0.006), and eosinophil percentage (mean difference, -8.73%; 95% CI, -12.88% to -4.58%; p < 0.001). One patient reported transient cognitive symptom worsening. Transcriptomic analysis showed downregulation of C-X-C motif chemokine receptor 4 (CXCR4) and matrix metallopeptidase 9 (MMP-9), and reduced interleukin-8- and type I interferon-related inflammation.

CONCLUSION

Dupilumab combined with TG is a promising corticosteroid-sparing treatment strategy for moderate-to-severe BP. Dupilumab likely contributed substantially to disease control, while TG may have provided adjunctive immunomodulatory effects. Transcriptomic findings point to CXCR4 and MMP-9 as candidate markers distinguishing pre- versus post-treatment samples, warranting external validation.