{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:21:07Z","timestamp":1791415267548,"version":"4.3.3"},"reference-count":133,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs\/MAPKs\/NF-\u03baB\/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.<\/jats:p>","DOI":"10.3390\/cells9081876","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T10:56:12Z","timestamp":1597143372000},"page":"1876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Small Molecule Inhibitors in the Treatment of Rheumatoid Arthritis and Beyond: Latest Updates and Potential Strategy for Fighting COVID-19"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-1100","authenticated-orcid":false,"given":"Magdalena","family":"Massalska","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wlodzimierz","family":"Maslinski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-6130","authenticated-orcid":false,"given":"Marzena","family":"Ciechomska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/art.30155","article-title":"The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases","volume":"63","author":"Crowson","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00019053-200422001-00002","article-title":"Epidemiology and burden of illness of rheumatoid arthritis","volume":"22","author":"Kvien","year":"2004","journal-title":"Pharmacoeconomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1136\/annrheumdis-2019-215294","article-title":"Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: A study among rheumatologists and patients from 44 European countries","volume":"78","author":"Putrik","year":"2019","journal-title":"Ann. 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