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At baseline and 3\u00a0months after treatment, clinical and functional assessments were done through the 28-joint count disease activity score using C-reactive protein (DAS28-CRP), the health assessment questionnaire-disability index (HAQ-DI), and the patient\u2019s global assessment (PGA). Also, serum levels of high-sensitivity C-reactive protein (hs-CRP), signal transducer and activator of transcription-3 (STAT-3), Janus kinase-2 (JAK-2), toll-like receptors 4 (TLR-4), interleukin-1 beta (IL-1\u03b2), and malondialdehyde (MDA) were assessed. Data were analyzed using paired\n t<\/jats:italic>\n -test and one-way analysis of variance, followed by Tukey\u2019s HDS test.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Three months after treatment and as compared to the control group, the nitazoxanide group showed a significant decline in PGA (\n P<\/jats:italic>\n \u2009=\u20090.042), and serum levels of STAT-3 (\n P<\/jats:italic>\n \u2009<\u20090.001), JAK-2 (\n P<\/jats:italic>\n \u2009<\u20090.001), TLR-4 (\n P<\/jats:italic>\n \u2009<\u20090.001), and IL-1\u03b2 (\n P<\/jats:italic>\n \u2009<\u20090.001). On the other hand, the escitalopram group produced a significant decrease in DAS28-CRP score (\n P<\/jats:italic>\n \u2009=\u20090.029), HAQ-DI score (\n P<\/jats:italic>\n \u2009=\u20090.001), and serum levels of JAK-2 (\n P<\/jats:italic>\n \u2009=\u20090.001), TLR-4 (\n P<\/jats:italic>\n \u2009<\u20090.001), IL-1\u03b2 (\n P<\/jats:italic>\n \u2009<\u20090.001), and MDA (\n P<\/jats:italic>\n \u2009<\u20090.001). As compared to nitazoxanide group, the escitalopram group produced a significant decline in fatigue score (\n P<\/jats:italic>\n \u2009<\u20090.001) and serum levels of both IL-1\u03b2 (\n P<\/jats:italic>\n \u2009=\u20090.023) and MDA (\n P<\/jats:italic>\n \u2009<\u20090.001). Both medications were safe; however, chromaturia was the only significant nitazoxanide-related adverse effect.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Nitazoxanide and escitalopram could serve as potential adjuvant therapies for patients with RA based on their effectiveness and safety data.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00228-025-03911-w","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T20:26:55Z","timestamp":1757449615000},"page":"1819-1832","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of nitazoxanide and escitalopram as adjuvant therapies in patients with rheumatoid arthritis: a randomized controlled study"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-5416","authenticated-orcid":false,"given":"Tarek M.","family":"Mostafa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-2087","authenticated-orcid":false,"given":"Abeer A.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-3530","authenticated-orcid":false,"given":"Abdel Moaty A.","family":"Afifi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-4637","authenticated-orcid":false,"given":"Dalia R.","family":"El-Afify","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"3911_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.1","volume":"4","author":"JS Smolen","year":"2018","unstructured":"Smolen JS, Aletaha D, Barton A et al (2018) Rheumatoid arthritis. 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