{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:12:19Z","timestamp":1788455539731,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening auto-inflammatory disease. Currently, there are no consensus-based guidelines or universally accepted treatments. Biologics represent a potential therapeutic option. This study systematically assessed the efficacy and safety of biologics in GPP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Relevant studies from three databases were systematically searched until June 28, 2024. Statistical information, including the single-arm proportion rate of the outcomes and 95% confidence intervals (CIs), was analyzed to determine treatment effects. Heterogeneity was assessed using I\u00b2 values, and subgroup analyses were performed based on drug targets and treatment durations. Data were quantitatively synthesized using a random-effects meta-analysis. Analyses were performed using R statistical software version 4.4.0.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 329 patients from 16 studies were included. The proportion of responders treated with IL-36 inhibitors and IL-17 inhibitors is higher than those treated with TNF-\u03b1 inhibitors and IL-23 inhibitors. IL-36 inhibitors appear to achieve the highest response rates between 4 and 8 weeks, while IL-17 inhibitors, TNF-alpha inhibitors, and IL-23 inhibitors show a gradual increase in response rates up to 12 weeks. IL-36 inhibitors achieve a 40% (95% CI: 27%-54%) GPPASI75 response rate and a 55% (95% CI: 41%-68%) GPPGA (0,1) response rate within 2 weeks, significantly outperforming other biologics. The recurrence rates of GPP within 52 weeks, ranked from highest to lowest, are: IL-36 inhibitors (21% [95% CI: 9%-28%]), TNF-alpha inhibitors (20% [95% CI: 2%-46%]), IL-17 inhibitors (15% [95% CI: 1%-37%]), and IL-23 inhibitors (5% [95% CI: 0%-29%]). Additionally, 6% (95% CI: 1%-11%) of patients experienced severe adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This meta-analysis highlights the efficacy and safety of biologics in patients with GPP, offering valuable evidence to guide future clinical practice. IL-36 inhibitors show a faster and more substantial clinical response in GPP compared to other biologics. Further research is necessary to assess their role in specific subpopulations and to evaluate their potential long-term effects on flare prevention.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1462158","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:50:59Z","timestamp":1728881459000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Biologics for generalized pustular psoriasis: a systematic review and single-arm meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Bai-lin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-wan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-ping","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.2014.53.issue-6","article-title":"Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia","volume":"53","author":"Choon","year":"2014","journal-title":"Int J Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-021-00654-z","article-title":"Clinical course and characteristics of generalized pustular psoriasis","volume":"23","author":"Choon","year":"2022","journal-title":"Am J Clin Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2019.1708193","article-title":"The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review","volume":"16","author":"Kharawala","year":"2020","journal-title":"Expert Rev Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.06.008","article-title":"Treatments and outcomes of generalized pustular psoriasis: A cohort of 1516 patients in a nationwide inpatient database in Japan","volume":"86","author":"Miyachi","year":"2022","journal-title":"J Am Acad Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/exd.2018.27.issue-10","article-title":"Generalized pustular psoriasis - a model disease for specific targeted immunotherapy, systematic review","volume":"27","author":"Boehner","year":"2018","journal-title":"Exp Dermatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.2018.32.issue-10","article-title":"Generalized pustular psoriasis: a review and update on treatment","volume":"32","author":"Hoegler","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.11.057","article-title":"Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics","volume":"80","author":"Menter","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2020.1785427","article-title":"Biologics in the treatment of pustular psoriasis","volume":"19","author":"Wang","year":"2020","journal-title":"Expert Opin Drug Saf"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","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 (london england)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1359481","article-title":"Spesolimab for generalized pustular psoriasis: a review of two key clinical trials supporting initial US regulatory approval","volume":"15","author":"Gwillim","year":"2024","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj"},{"key":"B15","article-title":"Japanese dermatological guidelines for general pustular psoriasis","author":"Association","year":"2015"},{"key":"B16","article-title":"Practice guidelines 2014 for generalized pustular psoriasis (GPP)","volume":"125","author":"Terui","year":"2015","journal-title":"Jpn J Dermatol"},{"key":"B17","first-page":"815","article-title":"Practice guidelines 2010 for generalized pustular psoriasis (GPP): treatment guidelines incorporating TNF-\u03b1 inhibitor","volume":"120","author":"Iwatsuki","year":"2010","journal-title":"Jpn J Dermatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"Bmj"},{"key":"B19","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"Bmj"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.ED000142","article-title":"Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions","volume":"10","author":"Cumpston","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041662","article-title":"Interleukin-17 vs. Interleukin-23 inhibitors in pustular and erythrodermic psoriasis: A retrospective, multicentre cohort study","volume":"12","author":"Avallone","year":"2023","journal-title":"J Clin Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/jde.2016.43.issue-9","article-title":"Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: a 52-week analysis from phase III open-label multicenter Japanese study","volume":"43","author":"Imafuku","year":"2016","journal-title":"J Dermatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"109899","DOI":"10.1016\/j.clim.2024.109899","article-title":"Better efficacy, lower recurrence rate and decreased CD8(+)T(RM) with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China","volume":"259","author":"Lu","year":"2024","journal-title":"Clin Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/jde.2018.45.issue-12","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":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-021-00666-x","article-title":"Ixekizumab 80 mg every 2 weeks treatment beyond week 12 for Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis","volume":"12","author":"Morita","year":"2022","journal-title":"Dermatol Ther (Heidelb)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.09.040","article-title":"Real-world single-center experience with 10 cases of generalized pustular psoriasis successfully treated with ixekizumab","volume":"82","author":"Nagata","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.2019.33.issue-2","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"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-022-00741-x","article-title":"Efficacy and safety of certolizumab pegol in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: 52-week results","volume":"12","author":"Okubo","year":"2022","journal-title":"Dermatol Ther (Heidelb)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.2015.29.issue-6","article-title":"Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis","volume":"29","author":"Saeki","year":"2015","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/jde.2018.45.issue-5","article-title":"Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52-week, phase 3, multicenter, open-label study","volume":"45","author":"Sano","year":"2018","journal-title":"J Dermatol"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14702","article-title":"Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study","volume":"176","author":"Yamasaki","year":"2017","journal-title":"Br J Dermatol"},{"key":"B33","doi-asserted-by":"publisher","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":"B34","doi-asserted-by":"publisher","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":"B35","doi-asserted-by":"publisher","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":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222969","article-title":"Interleukin (IL)-17\/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses","volume":"15","author":"Mercurio","year":"2020","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.727956","article-title":"The role of IL-36 in the pathophysiological processes of autoimmune diseases","volume":"12","author":"Chen","year":"2021","journal-title":"Front Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2021.1951192","article-title":"Characteristics of hospitalizations and emergency department visits due to generalized pustular psoriasis in the United States","volume":"37","author":"Hanna","year":"2021","journal-title":"Curr Med Res Opin"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20305","article-title":"High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract","volume":"40","author":"Viguier","year":"2004","journal-title":"Hepatology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-022-00881-0","article-title":"Generalized pustular psoriasis: A review on clinical characteristics, diagnosis, and treatment","volume":"13","author":"Rivera-D\u00edaz","year":"2023","journal-title":"Dermatol Ther (Heidelb)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.04.031","article-title":"Management of adult generalized pustular psoriasis using biologics: A systematic review","volume":"89","author":"Abduelmula","year":"2023","journal-title":"J Am Acad Dermatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1462158\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:51:01Z","timestamp":1728881461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1462158\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2024.1462158"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1462158","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"article-number":"1462158"}}