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These agents can induce remission and control inflammation while improving patient outcomes. At the same time, concern persists about possible carcinogenic effects that could promote tumor development. This narrative review summarizes evidence on malignancy risk after using conventional DMARDs.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/risk-of-cancer-and-conventional-syntethic-dmards-a-narrative-review/376290/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/risk-of-cancer-and-conventional-syntethic-dmards-a-narrative-review/376290.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What are conventional DMARDs and how are they used in rheumatic diseases?","Question",{"text":113,"@type":114},"Conventional DMARDs are immunomodulating/immunosuppressive therapies used to treat rheumatic diseases. They can induce remission or control inflammation, improving patient outcomes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is there concern that conventional DMARDs may be linked to cancer?",{"text":118,"@type":114},"There is concern about carcinogenic potential, with immunosuppressive drugs possibly favoring tumor appearance. The review also discusses mechanisms such as immune surveillance dysfunction and tumorigenesis processes.",{"name":120,"@type":111,"acceptedAnswer":121},"How does methotrexate relate to malignancy risk in rheumatoid arthritis?",{"text":122,"@type":114},"Methotrexate is associated with the development of lymphoproliferative diseases in rheumatoid arthritis. Evidence discussed includes regression of LPD after MTX withdrawal, which supports a carcinogenic potential, alongside mixed findings on overall cancer risk in some studies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},376290,1790820441,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","REVIEW RHEUMATOLOGY  \nNorth Clin Istanb 2025;12(3):378–384 doi: 10. 14744/nci.2024.21976  \nRisk of cancer and conventional syntethic DMARDS: A narrative review  \n Thelma Skare,1  Jozélio Freire de Carvalho2  \n1Department of Rheumatology, Hospital Evangélico Mackenzie, Curitiba, PR, Brazil  \n2Institute for Health Science, Federal University of Bahia, Salvador, Brazil  \nABSTRACT  \nImmunosuppressors and immunomodulators are widely used for the treatment of rheumatic diseases. Among them are the conventional Disease-Modifying Antirheumatic Drugs (DMARDs) such as methotrexate, azathioprine, antimalarials, cyclosporine, etc. These drugs can induce remission or control inflammation, improving patients’ outcomes. Nevertheless, there is some concern that these drugs may have a carcinogenic potential, favoring the appearance of tumors. Herein, a narrative review of malignancy risk after using conventional DMARDs is done.  \nKeywords: Cancer; disease-modifying antirheumatic drugs; DMARDs; immunosuppressive drugs.  \nCite this article as: Skare T, de Carvalho JF. Risk of cancer and conventional syntethic DMARDS: A narrative review. North Clin Istanb 2025;12(3):378–384.  \nThe association of rheumatic diseases with cancer is  \nwell known. However, the mechanisms underlying this association are challenging to be studied as this link may be multifactorial. Immune-mediated rheumatic diseases may be associated with cancer due to shared environmental exposures, virus infections, or a shared genetic background [1]. In this instance, in rheumatoid arthritis (RA), tobacco exposure and Epstein Barr infection are common environmental triggers for both disorders: cancer and the rheumatic condition [2, 3]. Moreover, the dysfunctional immune surveillance seen in immune-mediated diseases may favor the cancer’s appearance. The development of lymphoproliferative diseases in Sjogren’s syndrome is a classic example of the increased risk of malignancy in this context. Excessive glandular B lymphocyte stimulation and impaired B cell apoptosis are considered to lead to tumorigenesis and B cell clonal expansion [1]. In RA, long-term inflammatory activity is also associated with increased tumor risk  \n[1]. Another point to consider is that several rheumatic conditions may present as paraneoplastic syndromes. Inflammatory myositis, mostly dermatomyositis, has been characteristically identified in this setting, usually in lung, breast, ovarian, and nasopharyngeal cancer and lymphomas [4, 5]. Even some connective tissue diseases may have clinical manifestations associated with cancer appearance. This is the case of lung fibrosis associated with lung cancer [6] and esophagitis with Barrett’s epithelium [7] in scleroderma.  \nThe increased risk of malignant diseases driven by exposure to drugs used to treat rheumatic diseases is an area of concern. Several medications, such as azathioprine, methotrexate, cyclophosphamide, etc., have tumorigenic effects [1].  \nThe association of cancer and conventional rheumatic disease-modifying drug treatment is the focus of this review.  \nReceived: January 30, 2024 Accepted: March 18, 2024 Online: June 19, 2025  \nCorrespondence: Jozélio Freire de CARVALHO, MD. Institute for Health Science, Federal University of Bahia, Salvador, Brazil.  \nTel: +5571 99187-1169 e-mail: [jotafc@gmail.com](jotafc@gmail.com)  \nIstanbul Provincial Directorate of Health-Available online [at www.northclinist.com](at www.northclinist.com)  \nMETHOTREXATE (MTX)   \nMTX is widely used in rheumatology; it is considered the gold standard treatment in RA and is used asa steroid-sparing agent in several other rheumatological conditions. Despite a favorable side-effect profile, it has been associated with the appearance of solid tumorsand lymphomas. In patients with RA, the use of MTX is linked to the development of lymphoproliferative diseases (LPD), and the regression of the LPD after MTX withdrawal is considered strong evidence for the carcinogenic potential of this ","cbCaiixmaULjhPn9","https://ap.wps.com/l/cbCaiixmaULjhPn9","pdf",197120,"English","# Background and rationale\n## Rheumatic diseases and cancer link\n## Paraneoplastic syndromes and clinical associations\n# Drug-related malignancy concern\n## Tumorigenic effects of conventional DMARDs\n# Methotrexate (MTX)\n## MTX use in rheumatology\n## MTX and lymphoproliferative diseases (LPD)\n## Clinical studies and risk findings","[{\"question\":\"What are conventional DMARDs and how are they used in rheumatic diseases?\",\"answer\":\"Conventional DMARDs are immunomodulating/immunosuppressive therapies used to treat rheumatic diseases. They can induce remission or control inflammation, improving patient outcomes.\"},{\"question\":\"Why is there concern that conventional DMARDs may be linked to cancer?\",\"answer\":\"There is concern about carcinogenic potential, with immunosuppressive drugs possibly favoring tumor appearance. The review also discusses mechanisms such as immune surveillance dysfunction and tumorigenesis processes.\"},{\"question\":\"How does methotrexate relate to malignancy risk in rheumatoid arthritis?\",\"answer\":\"Methotrexate is associated with the development of lymphoproliferative diseases in rheumatoid arthritis. Evidence discussed includes regression of LPD after MTX withdrawal, which supports a carcinogenic potential, alongside mixed findings on overall cancer risk in some studies.\"}]","Risk of cancer and conventional syntethic DMARDS - A narrative review | PDF",1790218081,18]