{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:18Z","timestamp":1787015658753,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acne vulgaris is a common inflammatory skin disorder with significant psychosocial impact. While isotretinoin remains the gold standard for moderate\u2010to\u2010severe cases, its adverse effects and teratogenicity underscore the need for alternative systemic therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To review emerging systemic treatments for acne beyond isotretinoin, evaluating their efficacy, safety, and potential clinical applications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A narrative review was conducted through PubMed, Scopus, and Web of Science, including studies from January 2015 to June 2025. Eligible publications focused on systemic treatments for moderate\u2010to\u2010severe acne, excluding topical\u2010only and non\u2010peer\u2010reviewed studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Promising alternatives include the narrow\u2010spectrum antibiotic sarecycline, hormonal agents such as spironolactone and combined oral contraceptives, and metformin in patients with polycystic ovary syndrome. Biologic therapies, phosphodiesterase\u20104 inhibitors, oral probiotics, and novel agents like montelukast and CAMP factor vaccines are also under investigation. These treatments show varying degrees of efficacy and improved safety profiles, but most lack head\u2010to\u2010head comparisons with isotretinoin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Several systemic options beyond isotretinoin have emerged, showing potential in specific subgroups or as adjunctive therapies. However, further large\u2010scale comparative studies are needed to define their roles within evidence\u2010based acne management algorithms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70812","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T12:07:05Z","timestamp":1774958825000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond Isotretinoin: A Narrative Review of Emerging Systemic Therapies for Moderate\u2010to\u2010Severe Acne"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7997-1784","authenticated-orcid":false,"given":"Nello","family":"Tommasino","sequence":"first","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-0592","authenticated-orcid":false,"given":"Luca","family":"Potestio","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3309-8190","authenticated-orcid":false,"given":"Maddalena","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Section of Dermatology, Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abd.2022.01.006"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/AHMT.S55832"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.25588.1"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21081063"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2015.4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S106462"},{"key":"e_1_2_12_7_2","doi-asserted-by":"crossref","unstructured":"Published Correction Appears inDrug Design Development and Therapy10 (2016): 1549 https:\/\/doi.org\/10.2147\/DDDT.S109682.","DOI":"10.2147\/DDDT.S109682"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.40"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010024\u201003557\u2010y"},{"issue":"9","key":"e_1_2_12_10_1","first-page":"987","article-title":"Once\u2010Daily Oral Sarecycline 1.5 Mg\/Kg\/Day Is Effective for Moderate to Severe Acne Vulgaris: Results From Two Identically Designed, Phase 3, Randomized, Double\u2010Blind Clinical Trials","volume":"17","author":"Moore A.","year":"2018","journal-title":"Journal of Drugs in Dermatology"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.36849\/JDD.SF405634"},{"issue":"11","key":"e_1_2_12_12_1","first-page":"E53","article-title":"Safety and Tolerability of Sarecycline for the Treatment of Acne Vulgaris: Results From a Phase III, Multicenter, Open\u2010Label Study and a Phase I Phototoxicity Study","volume":"12","author":"Pariser D. M.","year":"2019","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12010094"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.36849\/JDD.2021.6204"},{"issue":"5","key":"e_1_2_12_15_1","first-page":"56","article-title":"An Open\u2010Label Study Comparing Oral Zinc to Lymecycline in the Treatment of Acne Vulgaris","volume":"14","author":"Tolino E.","year":"2021","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12540"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2013.6678"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1187186"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S384346"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2021.05.029"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.211155"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13030516"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2022.2138691"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15637"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16071"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21238960"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010020\u201000565\u20105"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.12953"},{"issue":"5","key":"e_1_2_12_29_1","first-page":"34","article-title":"Efficacy of Metformin in the Treatment of Acne in Women With Polycystic Ovarian Syndrome: A Newer Approach to Acne Therapy","volume":"12","author":"Sharma S.","year":"2019","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0015\u20100282(00)00501\u2010x"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12673"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25105302"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1425675"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3920\/BM2016.0089"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555\u2010021\u201000664\u2010z"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.23736\/S2784\u20108671.22.07361\u20103"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.2310\/7750.2012.12026"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010016\u20100245\u2010x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.14428"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.2340\/actadv.v104.26002"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.03.051"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.02.036"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.17964"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14462"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.4103\/1735-1995.158270"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15770"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21739"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.23736\/S2784\u20108671.25.08200\u20103"},{"issue":"3","key":"e_1_2_12_49_1","first-page":"333","article-title":"Efficacy and Safety of Sarecycline, a Novel, Once\u2010Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose\u2010Ranging Study","volume":"17","author":"Leyden J. J.","year":"2018","journal-title":"Journal of Drugs in Dermatology"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1370\/afm.2995"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010025\u201003840\u20106"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.5114\/ada.2021.107101"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17060728"}],"container-title":["Journal of Cosmetic Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.70812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jocd.70812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jocd.70812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T09:22:27Z","timestamp":1782292947000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jocd.70812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/jocd.70812"],"URL":"https:\/\/doi.org\/10.1111\/jocd.70812","archive":["Portico"],"relation":{},"ISSN":["1473-2130","1473-2165"],"issn-type":[{"value":"1473-2130","type":"print"},{"value":"1473-2165","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2025-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70812"}}