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Traditional non-biologic drugs, such as conventional synthetic DMARDs, are still widely used in rheumatology but in many cases the mechanisms of action of these drugs are unclear or multifaceted. A better understanding of these drugs, their associated adverse effects and how they work in concert with biologic drugs might enable the design of new therapies and therapeutic strategies.
In this Focus on mechanisms of non-biologic anti-rheumatic drugs, the four specially commissioned Reviews and one Perspectives article examine the cellular and molecular mechanisms underlying the therapeutic and adverse effects of various commonly used non-biologic drugs in rheumatology, as well as future prospects in this field. These drugs include methotrexate, hydroxychloroquine and glucocorticoids, as well as mycophenolate mofetil, azathioprine and tacrolimus.
Breakthroughs in the field of rheumatology have transformed the management of rheumatic diseases and improved patient outcomes, but clinical challenges remain. Looking back at ‘older’ drugs could provide new lessons for future drug strategies and development.
Glucocorticoids are anti-inflammatory therapies commonly used in rheumatology, but have wide-ranging adverse effects. Understanding the pharmacokinetic properties and mechanisms of action of glucocorticoids could inform in the development of novel therapies with fewer adverse effects.
Methotrexate can suppress inflammation via multiple mechanisms that can differ across different cell types. Understanding these mechanisms might enable better understanding of the disease and prediction of treatment responses.
Hydroxychloroquine and chloroquine are antimalarial drugs commonly used for the treatment of rheumatic diseases. Multiple mechanisms might explain the efficacy and adverse effects of these drugs, but further investigation could lead to the development of more specific and potent drugs.
Mycophenolate mofetil, azathioprine and tacrolimus are conventional DMARDs that originate in the field of transplantation medicine. This Review discusses the history, mechanisms, current indications and future prospects of these drugs in the field of rheumatology.