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

Si-Hang Wang,1 Si-Zhe Li,1 Yi-Ran Li,2 Jie Zhang,1 Yan Wang,1 Ya-Gang Zuo1 1Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Bioinformatics Facility, National Infrastructure for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Ya-Gang Zuo, Department of Dermatology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Hutong Dongcheng District, Beijing, 100730, People’s Republic of China, Email [email protected]: 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.Keywords: bullous pemphigoid, dupilumab, tripterygium glycoside, clinical efficacy, transcriptome sequencing