Efficacy and Safety of Dupilumab in Immune Checkpoint Inhibitor Induced Bullous Pemphigoid: A Spanish Multicentric Case Series

Authors

  • Cecilia Tejero-García Department of Dermatology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Translational Research Group in Dermatologic Diseases, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain https://orcid.org/0009-0004-6625-5599
  • Francesc Alamon Reig Department of Dermatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain https://orcid.org/0000-0002-6018-9680
  • Xavier Bosch-Amate Department of Dermatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain https://orcid.org/0000-0002-4809-8866
  • Cristina Carrera Department of Dermatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras CIBERER, Instituto de Salud Carlos III, Madrid, Spain https://orcid.org/0000-0003-1608-8820
  • Priscila Giavedoni Department of Dermatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain https://orcid.org/0000-0002-1474-9261
  • Inmaculada Gil Faure Department of Dermatology, Hospital Universitari Sant Joan de Reus, Tarragona, Spain https://orcid.org/0009-0008-7733-3539
  • Alicia Jiménez Antón Department of Dermatology, Hospital Universitario Puerta del Mar, Cádiz, Spain https://orcid.org/0000-0002-0623-8744
  • Ander Mayor Ibarguren Department of Dermatology, Hospital Universitario La Paz, Madrid, Spain https://orcid.org/0000-0003-1585-5995
  • Teresa Usero Bárcena Department of Dermatology, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain https://orcid.org/0009-0004-5124-0570
  • Marcial Álvarez-Salafranca Department of Dermatology, Hospital Universitario Miguel Servet, Zaragoza, Spain; University of Zaragoza, Zaragoza, Spain https://orcid.org/0000-0002-1691-3280
  • Marta Gamissans Cañada Department of Dermatology, Hospital Universitario Bellvitge, Barcelona, Spain https://orcid.org/0000-0002-7562-9458
  • Joaquín López Robles Department of Dermatology, Hospital General Universitario Morales Meseguer, Murcia, Spain https://orcid.org/0000-0003-0995-6802
  • Sandra Martínez-Fernández Department of Dermatology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain; DIPO Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Pontevedra, Spain https://orcid.org/0000-0003-4534-7828
  • Sonia Segura Department of Dermatology, Hospital del Mar, Barcelona, Spain https://orcid.org/0000-0003-0653-1382
  • Dolores Sánchez-Aguilar Rojas Department of Dermatology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Translational Research Group in Dermatologic Diseases, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; University of Santiago de Compostela, Santiago de Compostela, Spain https://orcid.org/0009-0003-1930-2666
  • Ángeles Flórez Department of Dermatology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Translational Research Group in Dermatologic Diseases, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; University of Santiago de Compostela, Santiago de Compostela, Spain https://orcid.org/0000-0001-9373-7826

DOI:

https://doi.org/10.2340/actadv.v106.adv-2026-0588

Keywords:

Dupilumab, Immune Checkpoint Inhibitors, Immunotherapy, Pemphigoid, Bullous, Safety, Treatment Outcome

Abstract

Immune checkpoint inhibitors (ICIs) have signifi-cantly improved oncologiconcological outcomes. However, ICIs can elicit immune-mediated adverse effects that may require treatment discontinuation and potentially affect cancer prognosis. Bullous pemphigoid (BP) can be induced by ICIs in up to 1 % of treated patients. Conventional treatments for BP (topical and systemic glucocorticoids as well as other classical immunosuppressants) associate substantial toxicities and may impair antitumour responses. Dupilumab, a monoclonal antibody that blocks IL-4/IL-13 signalling, represents a promising alternative, offering effective disease control with an improved safety profile. In this study, we assessed the efficacy and safety of dupilumab for the treatment of ICI-induced BP (ICI-BP) in a real-world multicentre case series of 19 patients, an underreported clinical setting. The median time to ICI-BP development from ICI initiation was 390 days (IQR 295). Overall, 18 patients (94.74%) achieved a clinical response, of whom 16 (84.21%) attained complete remission. Disease stabilization was observed in one1 patient. Among 17 patients receiving systemic corticosteroids prior to dupilumab, 14 (82.35%) discontinued them afterwards. Additionally, 11 patients (61.11 %; n=18) were able to continue or reintroduce ICI after dupilumab initiation. Dupilumab was well tolerated, with 18 patients (94.74%) experiencing no significant adverse events and only one case of suspected psoriasiform toxicity.

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References

Huang L, Zhu H, Shi Y. Immune checkpoint inhibitors for the treatment of solid tumors and lymphoma in the past 26 years (2000-2025). J Hematol Oncol 2025; 18: 107. DOI: https://doi.org/10.1186/s13045-025-01734-x

Sokołowski M, Sokołowska A, Chrząszcz M, Butrym A. Immune Checkpoint Inhibitors (ICI) in urological cancers: a new modern era, but not generally applied. Int J Mol Sci 2025; 26: 7194. DOI: https://doi.org/10.3390/ijms26157194

Jayathilaka B, Mian F, Franchini F, Au-Yeung G, IJzerman M. Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review. Br J Cancer 2025; 132: 51–57. DOI: https://doi.org/10.1038/s41416-024-02887-1

Watanabe T, Yamaguchi Y. Cutaneous manifestations associated with immune checkpoint inhibitors. Front Immunol 2023; 14: 1071983. DOI: https://doi.org/10.3389/fimmu.2023.1071983

Fattore D, Lauletta G, Pages C, Theret V, Sibaud V. Update on dermatological toxicities of immune checkpoint inhibitors. Presse Med 2025; 55: 104330. DOI: https://doi.org/10.1016/j.lpm.2025.104330

de Nicolas-Ruanes B, Ballester-Martinez A, Garcia-Mouronte E, Berna-Rico E, Azcarraga-Llobet C, Fernandez-Guarino M. From molecular insights to clinical perspectives in drug-associated bullous pemphigoid. Int J Mol Sci 2023; 24: 16786. DOI: https://doi.org/10.3390/ijms242316786

Apalla Z, Nikolaou V, Fattore D, Fabbrocini G, Freites-Martinez A, Sollena P, et al. European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force “Dermatology for cancer patients” position statement. J Eur Acad Dermatol Venereol 2022; 36: 332–350. DOI: https://doi.org/10.1111/jdv.17855

Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol 2021; 39: 4073–4126. DOI: https://doi.org/10.1200/JCO.21.01440

Borradori L, Van Beek N, Feliciani C, Tedbirt B, Antiga E, Bergman R, et al. Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol 2022; 36: 1689–1704. DOI: https://doi.org/10.1111/jdv.18220

Regeneron Pharmaceuticals Inc. DUPIXENT (dupilumab) injection, for subcutaneous use [prescribing information]. Tarrytown (NY): Regeneron Pharmaceuticals Inc; 2017.

Lambert RA, Block BR, Hu BD, Thakker S, Powers CM, Rabinowitz G, et al. Immune checkpoint inhibitor-induced bullous pemphigoid: a clinical review. JAAD Rev 2026; 7: 42–51. DOI: https://doi.org/10.1016/j.jdrv.2025.11.002

Wang Y, Yang LYY, Zuo YG. Refined pharmacovigilance assessment of immune checkpoint inhibitors-related bullous pemphigoid: a multi-methodological approach utilizing FAERS database. J Pharm Pharm Sci 2025; 28: 15597. DOI: https://doi.org/10.3389/jpps.2025.15597

Nykaza I, Moy A, Dusza SW, Moskowitz A, Iyer G, Iqbal A, et al. Dupilumab for bullous pemphigoid related to immune checkpoint inhibitors: a retrospective case series. Oncologist 2025; 30: oyaf208. DOI: https://doi.org/10.1093/oncolo/oyaf208

Tsiogka A, Bauer JW, Patsatsi A. Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: a review of the literature. Acta Derm Venereol 2021; 101: adv00377. DOI: https://doi.org/10.2340/00015555-3740

Pruessmann JN, Pruessmann W, Sadik CD. Research in practice: immune checkpoint inhibitor related autoimmune bullous dermatosis. J Dtsch Dermatol Ges 2025; 23: 441–445. DOI: https://doi.org/10.1111/ddg.15638

Rossi A, Brancorsini D, Gioacchini H, Campanati A. A case of pembrolizumab-induced bullous pemphigoid treated with dupilumab. Skin Health Dis 2025; 5: 70–74. DOI: https://doi.org/10.1093/skinhd/vzae023

Triantafillou V, Leahy K. Pembrolizumab-associated bullous pemphigoid with laryngeal involvement. Laryngoscope 2025; 135: 243–246. DOI: https://doi.org/10.1002/lary.31743

Florea CM, Parmentier L, Abdou M, Berthod G. Immune checkpoint inhibitor-induced bullous pemphigoid: successful treatment with dupilumab while maintaining immunotherapy. Case Rep Oncol 2025; 18: 1171–1177. DOI: https://doi.org/10.1159/000547431

Pop SR, Strock D, Smith RJ. Dupilumab for the treatment of pembrolizumab-induced bullous pemphigoid: a case report. Dermatol Ther 2022; 35: e15623. DOI: https://doi.org/10.1111/dth.15623

Grüninger J, Lehr S, Meiss F, Rafei D, Schauer F. Case report: dupilumab therapy for immune checkpoint inhibitor-induced bullous pemphigoid enables dual immunotherapy initiation in progressive malignant melanoma. Front Oncol 2025; 15: 1613552. DOI: https://doi.org/10.3389/fonc.2025.1613552

Hansen I, Gebhardt C, Booken N, Schneider SW. Successful treatment of checkpoint inhibitor-associated bullous pemphigoid with dupilumab in a patient with angiosarcoma. J Dtsch Dermatol Ges 2024; 22: 587–589. DOI: https://doi.org/10.1111/ddg.15340

Bruni M, Moar A, Schena D, Girolomoni G. A case of nivolumab-induced bullous pemphigoid successfully treated with dupilumab. Dermatol Online J 2022; 28. DOI: https://doi.org/10.5070/D328257396

Mihailescu ML, Brockstein BE, Desai N, Waldinger J. Successful reintroduction and continuation of nivolumab in a patient with immune checkpoint inhibitor-induced bullous pemphigoid. Curr Probl Cancer Case Rep 2020; 2: 100031. DOI: https://doi.org/10.1016/j.cpccr.2020.100031

Fournier C, Hirsch I, Spreafico A, Butler MO, Dhani N, Sauder MB. Dupilumab as a treatment for cutaneous immune-related adverse events induced by immune checkpoint inhibitors: a case series and review of the literature. SAGE Open Med Case Rep 2023; 11: 2050313X231195462. DOI: https://doi.org/10.1177/2050313X231195462

Shipman WD, Singh K, Cohen JM, Leventhal J, Damsky W, Tomayko MM. Immune checkpoint inhibitor-induced bullous pemphigoid is characterized by interleukin (IL)-4 and IL-13 expression and responds to dupilumab treatment. Br J Dermatol 2023; 189: 339–341. DOI: https://doi.org/10.1093/bjd/ljad149

Bogdanski E, Viveiros M, Chung C, Dulmage B. Immune checkpoint inhibitor induced bullous pemphigoid treated by dupilumab: a case series. J Am Acad Dermatol 2025; 93: AB222. DOI: https://doi.org/10.1016/j.jaad.2025.05.880

Giacchero D, Sibaud V, Gerard E, Lebbe C, Hirner J, Gaide O, et al. Dupilumab for immune checkpoint inhibitors-induced pruritic dermatoses: a retrospective, multicentric study. J Eur Acad Dermatol Venereol 2026; 40: e360–e363. DOI: https://doi.org/10.1111/jdv.70122

Planella-Fontanillas N, Bosch-Amate X, Jiménez Antón A, Moreno-Vílchez C, Guerrero MG, Blanes Martínez M del M, et al. Real-world evaluation of the effectiveness and safety of dupilumab in bullous pemphigoid: an ambispective multicentre case series. Br J Dermatol 2025; 192: 501–509. DOI: https://doi.org/10.1093/bjd/ljae403

Prasath S, Harsha SP, Swamy AM, Jayalingappa K, Kapoor M, Sundriyal D, et al. Revisiting the use of steroids in oncology. Med Oncol 2025; 43: 97. DOI: https://doi.org/10.1007/s12032-025-03214-1

Zhang S, Chen SD, Chen L, Hong B. Impact of glucocorticoid administration on therapeutic outcomes of immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis. Front Med 2023; 12. DOI: https://doi.org/10.3389/fmed.2025.1649353

Said JT, Liu M, Talia J, Singer SB, Semenov YR, Wei EX, et al. Risk factors for the development of bullous pemphigoid in US patients receiving immune checkpoint inhibitors. JAMA Dermatol 2022; 158: 552–557. DOI: https://doi.org/10.1001/jamadermatol.2022.0354

Chang L, Cui Y, Lu W, Zhao S, Zhuo Z. Immune checkpoint inhibitor-induced bullous pemphigoid: a systematic review of clinical characteristics and outcomes based on case reports. Front Immunol 2026; 17: 1745011. DOI: https://doi.org/10.3389/fimmu.2026.1745011

Pecci F, Thummalapalli R, Alden SL, Ricciuti B, Alessi JV, Elkrief A, et al. Factors associated with disease progression after discontinuation of immune checkpoint inhibitors for immune-related toxicity in patients with advanced non-small cell lung cancer. Clin Cancer Res 2025; 31: 2413–2425. DOI: https://doi.org/10.1158/1078-0432.CCR-24-2990

Yu Y, Zhou Y, Zhang X, Tan K, Zheng J, Li J, et al. Immune checkpoint inhibitors in the treatment of patients with cancer and preexisting psoriasis: a systematic review and meta-analysis of observational studies. Front Oncol 2022; 12: 934093. DOI: https://doi.org/10.3389/fonc.2022.934093

Su Z, Zeng YP. Dupilumab-associated psoriasis and psoriasiform manifestations: a scoping review. Dermatology 2023; 239: 646–657. DOI: https://doi.org/10.1159/000530608

Additional Files

Published

2026-05-21

How to Cite

Tejero-García, C., Alamon Reig, F., Bosch-Amate, X., Carrera, C., Giavedoni, P., Gil Faure, I., … Flórez, Ángeles. (2026). Efficacy and Safety of Dupilumab in Immune Checkpoint Inhibitor Induced Bullous Pemphigoid: A Spanish Multicentric Case Series. Acta Dermato-Venereologica, 106, adv–2026. https://doi.org/10.2340/actadv.v106.adv-2026-0588

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