{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:31:15Z","timestamp":1793345475305,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Generalized Pustular Psoriasis (GPP) is a rare and severe subtype of psoriasis that significantly impacts patients\u2019 quality of life. Until recently, no specific treatment modalities were available, and treatment for GPP followed the guidelines for the treatment of plaque psoriasis, consisting of conventional treatments, such as retinoids, methotrexate, and even biologics, which although effective in some cases, may be associated with significant side effects, necessitating more effective and safe options. The pathophysiology of Generalized Pustular Psoriasis is complex and not fully understood, but there is some overlap with the pathogenesis of Plaque Psoriasis. In GPP, the innate immune system seems to play a more significant role, with the interleukin (IL)-36 pathway being fundamentally involved. Spesolimab and imsidolimab, two recently developed therapeutic agents, target the IL-36 inflammatory pathway by binding to the IL-36 receptor (IL-36R). Both biologics have already been evaluated in phase 1 and 2 clinical trials and have shown promising results in terms of safety and efficacy. IL-36 receptor inhibitors demonstrated great efficacy and good safety profile in the management of patients with GPP, demonstrating their potential to emerge as a leading treatment option. This review aims to explore and summarize the current scientific literature on the most recently developed treatments for GPP.<\/jats:p>","DOI":"10.3390\/pharmaceutics16070908","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["New and Emerging Treatments for Generalized Pustular Psoriasis: Focus on IL-36 Receptor Inhibitors"],"prefix":"10.3390","volume":"16","author":[{"given":"Jo\u00e3o","family":"Vila\u00e7a","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7764-3229","authenticated-orcid":false,"given":"Orhan","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-0870","authenticated-orcid":false,"given":"Tiago","family":"Torres","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Dermatology, Centro Hospitalar Universit\u00e1rio do Porto, 4099-011 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1080\/1744666X.2019.1648209","article-title":"An update on generalized pustular psoriasis","volume":"15","author":"Gooderham","year":"2019","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3892\/ijmm.2021.4951","article-title":"An update on genetic basis of generalized pustular psoriasis (Review)","volume":"47","author":"Zhou","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/exd.13699","article-title":"Generalized pustular psoriasis\u2014A model disease for specific targeted immunotherapy, systematic review","volume":"27","author":"Boehner","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40257-021-00664-x","article-title":"The Prevalence and Disease Characteristics of Generalized Pustular Psoriasis","volume":"23","author":"Zheng","year":"2022","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s13555-022-00881-0","article-title":"Generalized Pustular Psoriasis: A Review on Clinical Characteristics, Diagnosis, and Treatment","volume":"13","author":"Carrascosa","year":"2023","journal-title":"Dermatol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1111\/jdv.14949","article-title":"Generalized pustular psoriasis: A review and update on treatment","volume":"32","author":"Hoegler","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.25259\/IJDVL_542_2022","article-title":"Pustular psoriasis: A distinct aetiopathogenic and clinical entity","volume":"90","author":"Vasudevan","year":"2023","journal-title":"Indian. J. Dermatol. Venereol. Leprol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1080\/1744666X.2021.1961580","article-title":"Generalized pustular psoriasis: Current management status and unmet medical needs in Japan","volume":"17","author":"Komine","year":"2021","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/1744666X.2022.2116003","article-title":"Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: Evidence and expert opinion","volume":"18","author":"Bachelez","year":"2022","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.12788\/cutis.0579","article-title":"Generalized Pustular Psoriasis: A Review of the Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment","volume":"110","author":"Reynolds","year":"2022","journal-title":"Cutis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1111\/exd.14765","article-title":"Current management of generalized pustular psoriasis","volume":"32","author":"Kodali","year":"2023","journal-title":"Exp. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s40257-021-00655-y","article-title":"Pathophysiology of Generalized Pustular Psoriasis","volume":"23","author":"Marrakchi","year":"2022","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jdermsci.2021.11.009","article-title":"Pustular psoriasis as an autoinflammatory keratinization disease (AiKD): Genetic predisposing factors and promising therapeutic targets","volume":"105","author":"Akiyama","year":"2022","journal-title":"J. Dermatol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1007\/s13555-021-00612-x","article-title":"Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options","volume":"11","author":"Menter","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Genovese, G., Moltrasio, C., Cassano, N., Maronese, C.A., Vena, G.A., and Marzano, A.V. (2021). Pustular Psoriasis: From Pathophysiology to Treatment. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121746"},{"key":"ref_16","first-page":"753","article-title":"Generalized pustular psoriasis: Overview of the status quo and results of a panel discussion","volume":"20","author":"Reich","year":"2022","journal-title":"J. Dtsch. Dermatol. Ges. J. Ger. Soc. Dermatol. JDDG"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1056\/NEJMoa1013068","article-title":"Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis","volume":"365","author":"Makni","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1038\/jid.2014.46","article-title":"CARD14 c.526G>C (p.Asp176His) is a significant risk factor for generalized pustular psoriasis with psoriasis vulgaris in the Japanese cohort","volume":"134","author":"Sugiura","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1111\/bjd.15442","article-title":"Autosomal dominant familial generalized pustular psoriasis caused by a CARD14 mutation","volume":"177","author":"Takeichi","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.ajhg.2014.04.005","article-title":"AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking","volume":"94","author":"Simpson","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.jid.2019.11.024","article-title":"Rare loss-offunction mutation in SERPINA3 in generalized pustular psoriasis","volume":"140","author":"Frey","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ajhg.2020.07.001","article-title":"Myeloperoxidase modulates inflammation in generalized pustular psoriasis and additional rare pustular skin diseases","volume":"107","author":"Haskamp","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.4103\/0366-6999.184470","article-title":"Tumor necrosis factor-alpha induced protein 3 interacting protein 1 gene polymorphisms and pustular psoriasis in Chinese Han population","volume":"129","author":"Han","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40257-021-00658-9","article-title":"Treatment Options and Goals for Patients with Generalized Pustular Psoriasis","volume":"23","author":"Krueger","year":"2022","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1080\/09546634.2019.1682502","article-title":"Review of treatments for generalized pustular psoriasis","volume":"32","author":"Kearns","year":"2021","journal-title":"J. Dermatol. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1177\/1203475418773358","article-title":"Systemic Monotherapy Treatments for Generalized Pustular Psoriasis: A Systematic Review","volume":"22","author":"Zhou","year":"2018","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3892\/etm.2022.11463","article-title":"Use of granulocyte and monocyte adsorption apheresis in dermatology (Review)","volume":"24","author":"Gnesotto","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.2147\/CCID.S407812","article-title":"Use of Biological Therapies for the Management of Pustular Psoriasis: A New Era?","volume":"16","author":"Megna","year":"2023","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/1346-8138.14664","article-title":"Adalimumab treatment in Japanese patients with generalized pustular psoriasis: Results of an open-label phase 3 study","volume":"45","author":"Morita","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1358\/dot.2019.55.9.3020159","article-title":"The role of IL-17 and IL-17 receptor inhibitors in the management of generalized pustular psoriasis","volume":"55","author":"Plachouri","year":"2019","journal-title":"Drugs Today"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/jdv.15287","article-title":"Long-term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: Subgroup analyses of an open-label, phase 3 study (UNCOVER-J)","volume":"33","author":"Okubo","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1080\/14712598.2022.2116978","article-title":"Targeting IL-17A for the treatment of pustular psoriasis: A comprehensive review","volume":"22","author":"Rosi","year":"2022","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s40265-019-01136-7","article-title":"Risankizumab: First Global Approval","volume":"79","author":"McKeage","year":"2019","journal-title":"Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/1346-8138.16667","article-title":"Efficacy and safety of risankizumab in Japanese patients with generalized pustular psoriasis or erythrodermic psoriasis: Primary analysis and 180-week follow-up results from the phase 3, multicenter IMMspire study","volume":"50","author":"Yamanaka","year":"2023","journal-title":"J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s13555-022-00883-y","article-title":"Bimekizumab Efficacy and Safety in Japanese Patients with Plaque Psoriasis in BE VIVID: A Phase 3, Ustekinumab and Placebo-Controlled Study","volume":"13","author":"Asahina","year":"2023","journal-title":"Dermatol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/jdv.18820","article-title":"Spesolimab improves patient-reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study","volume":"37","author":"Navarini","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1007\/s40265-022-01801-4","article-title":"Spesolimab: First Approval","volume":"82","author":"Blair","year":"2022","journal-title":"Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJMc1811317","article-title":"Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis","volume":"380","author":"Bachelez","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s40265-023-01988-0","article-title":"Spesolimab for the Treatment of Generalized Pustular Psoriasis","volume":"84","author":"Bernardo","year":"2024","journal-title":"Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1056\/NEJMoa2111563","article-title":"Trial of Spesolimab for Generalized Pustular Psoriasis","volume":"385","author":"Bachelez","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/S0140-6736(23)01378-8","article-title":"Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): An international, multicentre, randomised, placebo-controlled trial","volume":"402","author":"Morita","year":"2023","journal-title":"Lancet"},{"key":"ref_42","unstructured":"Boehringer Ingelheim (2023, January 01). EffisayilTM ON: An Open-Label, Long Term Extension Study to Assess the Safety and Efficacy of Spesolimab Treatment in Patients with Generalized Pustular Psoriasis (GPP), Available online: https:\/\/clinicaltrials.gov\/study\/NCT03886246."},{"key":"ref_43","unstructured":"Boehringer Ingelheim (2024, January 01). Multi-Centre, Open-Label, Expanded Access Trial of Spesolimab i.v. in Patients with Generalized Pustular Psoriasis (GPP) Presenting with a Flare, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05200247."},{"key":"ref_44","unstructured":"Boehringer Ingelheim (2024, January 01). Multi-Centre, Open-Label, Expanded Access Program of 900 mg Intravenous (i.v.) Spesolimab in Patients with Generalized Pustular Psoriasis (GPP) Presenting with a Flare, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05239039."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1080\/09546634.2022.2067819","article-title":"A review of IL-36: An emerging therapeutic target for inflammatory dermatoses","volume":"33","author":"Hwang","year":"2022","journal-title":"J. Dermatol. Treat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/bjd\/ljad083","article-title":"Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: Results from the phase II GALLOP trial","volume":"189","author":"Warren","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_47","unstructured":"(2024, May 31). Anaptys News. San Diego. Montemarano N. Anaptys  Announces Positive Top-Line Phase 3 Clinical Trial Results of Imsidolimab (IL-36R) in Generalized Pustular Psoriasis (GPP). Available online: https:\/\/ir.anaptysbio.com\/news-releases\/news-release-details\/anaptys-announces-positive-top-line-phase-3-clinical-trial."},{"key":"ref_48","unstructured":"Shanghai Huaota Biopharmaceutical Co., Ltd. (2024, May 31). HB0034 in Patients with Generalized Pustular Psoriasis (GPP), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05512598."},{"key":"ref_49","unstructured":"Yang, B., Chen, J., Zhang, Z., Schwabe, C., Zhou, G., Wang, J., Ruan, W., Situ, X., Zhang, J., and Dai, L. (2023, January 11\u201314). HB0034, a novel anti-IL-36R inhibitor, showed a promising efficacy in controlling acute GPP flare. Proceedings of the 32nd EADV Congress, Berlin, Germany. Available online: https:\/\/s3.eu-central-1.amazonaws.com\/m-anage.com.storage.eadv\/abstracts_congress2023\/35021.pdf."},{"key":"ref_50","unstructured":"Takeda (2024, May 31). A Study of TAK-279 in Adult Participants with Generalized Pustular Psoriasis or Erythrodermic Psoriasis, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06323356."},{"key":"ref_51","unstructured":"Janssen Pharmaceutical, K.K. (2024, May 31). A Study of JNJ-77242113 for the Treatment of Participants with Generalized Pustular Psoriasis or Erythrodermic Psoriasis, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06295692."},{"key":"ref_52","unstructured":"Anaptys (2024, May 31). Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects with GPP (GEMINI1), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05352893."},{"key":"ref_53","unstructured":"Shanghai Huaota Biopharmaceutical Co., Ltd. (2024, May 31). A Study to Evaluate HB0034 in Healthy Adult Participants, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05064345."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/7\/908\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:11:07Z","timestamp":1760109067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/7\/908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,6]]},"references-count":53,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["pharmaceutics16070908"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16070908","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,6]]}}}