Conventional disease-modifying antirheumatic drugs (DMARDs) have been used in the management of rheumatoid arthritis for a long time. Whereas methotrexate (MTX) is the anchor drug, leflunomide, hydroxychloroquine and sulfasalazine are used along with MTX either in combination or sequentially. Together these four drugs are the most commonly used DMARDs. They are also used in combination with biological DMARDs (bDMARDs) to enhance their efficacy and MTX in particular to reduce antibodies against anti-tumour necrosis factor. Despite their widespread use, concerns regarding their safety especially when used long-term hinder their optimum use in clinical medicine. In this narrative review we have critically appraised the available literature regarding the safety of these four DMARDs when used long-term.
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