{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:58:02Z","timestamp":1789095482599,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/objective: Janus Kinase inhibitors (JAKinibs) are effective and well-tolerated targeted therapies for rheumatoid arthritis (RA). The comparative efficacy and safety of different JAKinibs remains unclear. This network meta-analysis (NMA) aimed to assess the relative efficacy and safety of different available JAKinibs. Methods: Searches were conducted on PubMed, CENTRAL, and ClinicalTrials.gov for randomized, double-blind, placebo-controlled trials comparing JAKinibs in RA patients. A frequentist NMA using the Netmeta package in R (R.4.3.0) was performed to evaluate both efficacy and safety outcomes. Continuous outcomes were presented as mean differences (MDs) and binary outcomes as relative risks (RR) with 95% confidence intervals (CI). The Cochrane risk of bias tool was used to assess the risk of bias in the included trials. Results: The analysis encompassed 39 trials with a total of 16,894 participants. Six JAKinibs (tofacitinib, baricitinib, upadacitinib, decernotinib, peficitinib, and filgotinib) were compared. Decernotinib at a dose of 300 mg showed a higher ACR50 response than other JAKinibs (RR = 7.55, 95% CI: 3.48 to 16.39, p &lt; 0.01, surface under the cumulative ranking curve (SUCRA): 0.92). Tofacitinib at a dose of 1 mg twice daily had a significantly lower incidence of adverse drug reactions (ADRs) compared to other JAKinibs (RR = 0.80, 95% CI: 0.65 to 0.99, p = 0.04, SUCRA: 0.89), filgotinib 100 mg had a significantly lower infection risk (RR = 0.40, 95% CI: 0.21 to 0.79, p &lt; 0.01, SUCRA: 0.90), whereas baricitinib 4 mg had the significantly highest herpes zoster risk (RR = 4.79, 95% CI: 1.03 to 22.21, p = 0.05, SUCRA: 0.11) compared to other JAKinibs. Conclusions: This NMA\u2019s results indicate that commercially available JAKinibs show superior ACR responses and have comparable tolerability to placebo.<\/jats:p>","DOI":"10.3390\/ph18020178","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:47:29Z","timestamp":1738046849000},"page":"178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparative Efficacy and Safety of JAK Inhibitors in the Management of Rheumatoid Arthritis: A Network Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-8317","authenticated-orcid":false,"given":"Hani M.","family":"Almoallim","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9373-5473","authenticated-orcid":false,"given":"Mohammed A.","family":"Omair","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-6846","authenticated-orcid":false,"given":"Sameh A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7866-0936","authenticated-orcid":false,"given":"Kota","family":"Vidyasagar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-619X","authenticated-orcid":false,"given":"Bisher","family":"Sawaf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Toledo University Medical Center, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Yassin","sequence":"additional","affiliation":[{"name":"Hematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","first-page":"e8094","article-title":"The Prevalence of Autoimmune Disorders in Women: A Narrative Review","volume":"12","author":"Angum","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Batko, B., Rolska-W\u00f3jcik, P., and W\u0142adysiuk, M. (2019). Indirect Costs of Rheumatoid Arthritis Depending on Type of Treatment-A Systematic Literature Review. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16162966"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4137\/CMAMD.S5558","article-title":"Pharmacotherapy options in rheumatoid arthritis","volume":"6","author":"Kumar","year":"2013","journal-title":"Clin. Med. 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