{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:18:16Z","timestamp":1789759096914,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"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>Rheumatoid arthritis (RA) is a systemic autoimmune disease that, beyond joint destruction, contributes to neuropsychiatric symptoms such as depression, anxiety, and cognitive impairment. These symptoms are often underrecognized despite their major impact on quality of life. Accumulating evidence suggests that pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6), play a key role in this neuroimmune interface. This narrative review examined 16 clinical studies evaluating the effects of biologic therapies targeting TNF-\u03b1 and IL-6 on mental health outcomes in RA. The total study population comprised 9939 patients, including 2467 treated with TNF-\u03b1 inhibitors and 7472 with IL-6 or IL-6 receptor inhibitors. TNF-\u03b1 inhibitors were associated with improved depressive symptoms and emotional well-being. IL-6 inhibitors demonstrated similar psychiatric benefits, particularly in patients with elevated IL-6 levels. The findings highlight that biological therapies in RA may influence not only physical symptoms but also mental health, likely through modulation of neuroimmune pathways including blood\u2013brain barrier permeability, microglial activation, and HPA axis regulation. Future research is needed to clarify these effects in populations stratified by psychiatric comorbidity and inflammatory biomarkers. Clinical implications: Incorporating psychiatric symptom screening and considering neuroinflammatory profiles may help guide the selection of biologic therapy in RA, particularly in patients with comorbid depression or fatigue.<\/jats:p>","DOI":"10.3390\/ijms26178361","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T11:41:12Z","timestamp":1756381272000},"page":"8361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Beyond Joints: Neuropsychiatric Benefits of TNF-\u03b1 and IL-6 Inhibitors in Rheumatoid Arthritis\u2014Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Hanna","family":"Siuchni\u0144ska","sequence":"first","affiliation":[{"name":"Occupational Therapy Center in Czersk ul Pomorska 10, 89-650 Czersk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Minarowska","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, School of Public Health, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Jagiello\u0144ska 78, 10-357 Olsztyn, Poland"},{"name":"Department of Pediatrics, Gastroenterology, Hepatology, Nutrition, Allergology and Pulmonology, Outpatient Cystic Fibrosis Clinic, Children\u2019s University Hospital in Bialystok, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5288-0586","authenticated-orcid":false,"given":"Eliza","family":"Wasilewska","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gda\u0144sk, Smoluchowskiego 17, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.semarthrit.2006.08.006","article-title":"Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: A systematic review","volume":"36","author":"Alamanos","year":"2006","journal-title":"Semin. 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