Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology

• Published in: Nature reviews. Rheumatology Vol. 16; no. 3; pp. 167 - 178
• Main Authors: Broen, Jasper C A, van Laar, Jacob M
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2020
• Subjects: Antirheumatic Agents - pharmacokinetics; Antirheumatic Agents - therapeutic use; Azathioprine; Azathioprine - pharmacokinetics; Azathioprine - therapeutic use; Calcineurin; Cell activation; Cell proliferation; Clinical trials; Drug Therapy, Combination; Drugs; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - therapeutic use; Fibrosis; Historical account; Humans; Immunosuppressive agents; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Lung diseases; Lupus nephritis; Lymphocytes; Medical treatment; Mycophenolate mofetil; Mycophenolic acid; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Nephritis; Patient outcomes; Pharmacodynamics; Pharmacology, Experimental; Rheumatic diseases; Rheumatic Diseases - drug therapy; Rheumatology; Skin diseases; Systemic sclerosis; Tacrolimus; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; Transplantation; Netherlands
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/s41584-020-0374-8

The introduction of biologic DMARDs into rheumatology has resulted in a substantial reduction of the burden of many rheumatic diseases. In the slipstream of the success achieved with these biologic DMARDs, some conventional immunosuppressive drugs have also found use in new indications. Notably, mycophenolate mofetil, azathioprine and tacrolimus have made their way from solid organ transplantation drugs to become useful assets in rheumatology practice. Mycophenolate mofetil and azathioprine inhibit the purine pathway and subsequently diminish cell proliferation. Both drugs have a pivotal role in the treatment of various rheumatic diseases, including lupus nephritis. Tacrolimus inhibits lymphocyte activation by inhibiting the calcineurin pathway. Mycophenolate mofetil and tacrolimus are, among other indications, increasingly being recognized as useful drugs in the treatment of interstitial lung disease in systemic rheumatic diseases and skin fibrosis in systemic sclerosis. A broad array of trials with mycophenolate mofetil, azathioprine and/or tacrolimus are ongoing within the field of rheumatology that might provide further novel avenues for the use of these drugs. In this Review, we discuss the historical perspective, pharmacodynamics, clinical indications and novel avenues for mycophenolate mofetil, azathioprine and tacrolimus in rheumatology.