Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology

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. 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. Key points Mycophenolate mofetil (MMF), azathioprine and tacrolimus are three conventional DMARDs that originate from the field of transplantation medicine, but have been repurposed for the treatment of rheumatic diseases. MMF and azathioprine both interfere with the purine pathway to inhibit cell proliferation, whereas tacrolimus inhibits calcineurin activity and subsequent lymphocyte activation. MMF and azathioprine are pivotal in the treatment of lupus nephritis. MMF and tacrolimus are, among other indications, increasingly recognized as useful drugs in the treatment of interstitial lung disease in systemic rheumatic diseases and skin fibrosis in systemic sclerosis. Future avenues for these drugs include the optimization of dosing schemes and investigation of novel indications and effects when co-administered with other DMARDs.