{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:41:14Z","timestamp":1788352874571,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development Institute (KHIDI)","award":["HP23C0146"],"award-info":[{"award-number":["HP23C0146"]}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["HP23C0146"],"award-info":[{"award-number":["HP23C0146"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-12\/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-\u03b1 inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12\/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-\u03b1, IL-23, and IL-12\/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis.<\/jats:p>","DOI":"10.3390\/jcm12247653","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:55:16Z","timestamp":1702457716000},"page":"7653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Incidence of New-Onset Inflammatory Bowel Disease, Oral and Gastrointestinal Candidiasis, Herpes Zoster, Pulmonary Tuberculosis, and Major Cardiovascular Events in Patients with Moderate-to-Severe Psoriasis Exposed to Biologics"],"prefix":"10.3390","volume":"12","author":[{"given":"Da-Hyun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bark-Lynn","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-5725","authenticated-orcid":false,"given":"Soon-Hyo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/jdv.12106","article-title":"Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): The correlation between disease severity and psychological burden in patients treated with biological therapies","volume":"28","author":"Mattei","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1111\/j.1365-2133.2005.06688.x","article-title":"A global phase III randomized controlled trial of etanercept in psoriasis: Safety, efficacy, and effect of dose reduction","volume":"152","author":"Papp","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/S0140-6736(08)60725-4","article-title":"Efficacy and safety of ustekinumab, a human interleukin-12\/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)","volume":"371","author":"Leonardi","year":"2008","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/S0140-6736(08)60726-6","article-title":"Efficacy and safety of ustekinumab, a human interleukin-12\/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)","volume":"371","author":"Papp","year":"2008","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJMoa1314258","article-title":"Secukinumab in plaque psoriasis\u2014Results of two phase 3 trials","volume":"371","author":"Langley","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jaad.2016.11.041","article-title":"Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial","volume":"76","author":"Blauvelt","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1029","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":"ref_8","doi-asserted-by":"crossref","unstructured":"Eshwar, V., Kamath, A., Shastry, R., Shenoy, A.K., and Kamath, P. (2022). A Review of the Safety of Interleukin-17A Inhibitor Secukinumab. Pharmaceuticals, 15.","DOI":"10.3390\/ph15111365"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.jid.2018.10.042","article-title":"Impact of Secukinumab on Endothelial Dysfunction and Other Cardiovascular Disease Parameters in Psoriasis Patients over 52 Weeks","volume":"139","author":"Reich","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12933-022-01524-6","article-title":"Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: A distributed network analysis of 10 real-world databases","volume":"21","author":"Seo","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2011.10.001","article-title":"Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review","volume":"142","author":"Molodecky","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/ijdvl.IJDVL_875_17","article-title":"Psoriasis increases the risk of concurrent inflammatory bowel disease: A population-based nationwide study in Korea","volume":"85","author":"Lee","year":"2019","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1136\/gutjnl-2011-301668","article-title":"Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn\u2019s disease: Unexpected results of a randomised, double-blind placebo-controlled trial","volume":"61","author":"Hueber","year":"2012","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13075-019-1882-2","article-title":"Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: Integrated pooled clinical trial and post-marketing surveillance data","volume":"21","author":"Deodhar","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1080\/14740338.2016.1221923","article-title":"Safety of secukinumab in the treatment of psoriasis","volume":"15","author":"Blauvelt","year":"2016","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1038\/jid.2015.144","article-title":"IL-23\/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL-17A Therapies","volume":"135","author":"Blauvelt","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.4049\/jimmunol.1001153","article-title":"IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans","volume":"185","author":"Kagami","year":"2010","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1080\/17512433.2022.2130758","article-title":"Why targeted therapeutics have provided benefit in psoriasis: Looking at IL-17 biology","volume":"15","author":"Lanna","year":"2022","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100266","DOI":"10.1016\/j.lanepe.2021.100266","article-title":"Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources","volume":"13","author":"Davidson","year":"2022","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/bjd.19341","article-title":"Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): Results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial","volume":"184","author":"Warren","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0140-6736(19)31773-8","article-title":"Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): Results from a phase 3, randomised controlled trial","volume":"394","author":"Reich","year":"2019","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1016\/j.jid.2022.05.1083","article-title":"Immunological Effects of Anti-IL-17\/12\/23 Therapy in Patients with Psoriasis Complicated by Candida Infections","volume":"142","author":"Bruno","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1007\/s12325-023-02568-0","article-title":"Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review","volume":"40","author":"Blauvelt","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8909834","DOI":"10.1155\/2017\/8909834","article-title":"Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics","volume":"2017","author":"Cantini","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1172\/JCI39143","article-title":"Anti-TNF immunotherapy and tuberculosis reactivation: Another mechanism revealed","volume":"119","author":"Miller","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1002\/hsr2.216","article-title":"Tuberculosis screening and management of latent tuberculosis infection prior to biologic treatment in patients with immune-mediated inflammatory diseases: A longitudinal population-based analysis using claims data","volume":"3","author":"Iba","year":"2020","journal-title":"Health Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fimmu.2017.00294","article-title":"Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases","volume":"8","author":"Mourik","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.jaad.2020.06.012","article-title":"No reactivation of tuberculosis in patients with latent tuberculosis infection receiving ixekizumab: A report from 16 clinical studies of patients with psoriasis or psoriatic arthritis","volume":"83","author":"Mrowietz","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jaad.2018.06.057","article-title":"Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents","volume":"80","author":"Kaushik","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1111\/jdv.16460","article-title":"Safety in moderate-to-severe plaque psoriasis patients with latent tuberculosis treated with guselkumab and anti-tuberculosis treatments concomitantly: Results from pooled phase 3 VOYAGE 1 & VOYAGE 2 trials","volume":"34","author":"Puig","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/14740338.2020.1736034","article-title":"A drug safety evaluation of risankizumab for psoriasis","volume":"19","author":"Huang","year":"2020","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/jdv.16866","article-title":"Risk of tuberculosis reactivation with interleukin (IL)-17 and IL-23 inhibitors in psoriasis\u2014Time for a paradigm change","volume":"35","author":"Nogueira","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/jdv.12307","article-title":"The risk of herpes zoster during biological therapy for psoriasis and other inflammatory conditions","volume":"28","author":"Adelzadeh","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"665559","DOI":"10.3389\/fmed.2021.665559","article-title":"Risk of Herpes Zoster Among Psoriasis Patients Taking Biologics: A Network Meta-Analysis of Cohort Studies","volume":"8","author":"Tang","year":"2021","journal-title":"Front. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1111\/jdv.19328","article-title":"Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors\u2014A population-based study","volume":"37","author":"Kridin","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"486","DOI":"10.5021\/ad.2019.31.4.486","article-title":"Population-Based Epidemiologic Study on Herpes Zoster in Korea: Seven-Year Nationwide Analysis from 2010 to 2016","volume":"31","author":"Kwon","year":"2019","journal-title":"Ann. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1001\/jama.296.14.1735","article-title":"Risk of myocardial infarction in patients with psoriasis","volume":"296","author":"Gelfand","year":"2006","journal-title":"JAMA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1038\/jid.2013.149","article-title":"Incidence of cardiovascular disease in individuals with psoriasis: A systematic review and meta-analysis","volume":"133","author":"Samarasekera","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/eurheartj\/ehs263","article-title":"Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction","volume":"34","author":"Simon","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1093\/cvr\/cvz009","article-title":"Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: Results from a prospective observational study","volume":"115","author":"Elnabawi","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s40744-022-00434-z","article-title":"Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications","volume":"9","author":"Merola","year":"2022","journal-title":"Rheumatol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wang, X., Kaiser, H., Kvist-Hansen, A., McCauley, B.D., Skov, L., Hansen, P.R., and Becker, C. (2022). IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010555"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.jid.2020.01.025","article-title":"A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S)","volume":"140","author":"Gelfand","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.jaad.2016.09.026","article-title":"Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data","volume":"76","author":"Strober","year":"2017","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/24\/7653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:37:57Z","timestamp":1760132277000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/24\/7653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,13]]},"references-count":44,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["jcm12247653"],"URL":"https:\/\/doi.org\/10.3390\/jcm12247653","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,13]]}}}