{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:47:22Z","timestamp":1790221642308,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sarcoidosis is a multisystem granulomatous disorder of uncertain origin which still presents major therapeutic dilemmas. Longstanding dependence on corticosteroids, while effective for acute inflammation, carries considerable adverse effects over time. Advances in deciphering sarcoidosis pathobiology\u2014including aberrant Janus kinase (JAK)- signal transducer and activator of transcription (STAT) signaling, mechanistic target of rapamycin (mTOR)-driven metabolic shifts, Th1\/Th17.1 immune skewing, effector T-cell exhaustion, and granuloma-centered cytokine circuits\u2014have revealed several targets for intervention. The treatment options are rapidly changing: the SARCORT trial showed that low-dose prednisolone is non-inferior to higher prednisolone doses; the pivotal PREDMETH trial validated methotrexate as a feasible first-line steroid-sparing option; efzofitimod, a novel immunomodulator targeting neuropilin-2, produced steroid-reducing effects in Phase IIbut not in Phase III trials; and JAK inhibitors are accumulating evidence across cutaneous and systemic presentations. The 2025 World Association for Sarcoidosis and Other Granulomatoses (WASOG) statement supports a move toward earlier steroid-sparing approaches. This review methodically connects sarcoidosis molecular and pathophysiological mechanisms to new targeted treatments, examines clinical trial evidence, and proposes future directions toward biomarker-driven individualized care.<\/jats:p>","DOI":"10.3390\/ijms27125335","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["New Therapies for Sarcoidosis: Molecular and Pathophysiological Basis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-291X","authenticated-orcid":false,"given":"Fotios","family":"Drakopanagiotakis","sequence":"first","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-2925","authenticated-orcid":false,"given":"Ilias","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Kerkyra General Hospital, 49100 Corfu, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6564-0267","authenticated-orcid":false,"given":"Theodoros","family":"Panou","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Gialafos","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Medical School, Aeginition Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4451-0836","authenticated-orcid":false,"given":"Nikolaos","family":"Kostakis","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Chytopoulos","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Bogiatzis","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7121-6253","authenticated-orcid":false,"given":"Paschalis","family":"Steiropoulos","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Medical School, Democritus University of Thrace, University General Hospital Dragana, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMra2101555","article-title":"Challenges of Sarcoidosis and Its Management","volume":"385","author":"Drent","year":"2021","journal-title":"N. 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