Revisiting the immunomodulators tacrolimus, methotrexate, and mycophenolate mofetil: their mechanisms of action and role in the treatment of IBD.
Inflammatory bowel diseases (IBDs) are thought to result from unopposed immune responses to normal gut flora in a genetically susceptible host. A variety of immunomodulating therapies are applied for the treatment of patients with IBDs. The first-line treatment for IBDs consists of 5-aminosalicylate and/or budesonide. However, these first-line therapies are often not suitable for continuous treatment or do not suffice for the treatment of severe IBD. Recently, efforts have been made to generate novel selective drugs that are more effective and have fewer side effects. Despite promising results, most of these novel drugs are still in a developmental stage and unavailable for clinical application. Yet, another class of established immunomodulators exists that is successful in the treatment of inflammatory bowel diseases. While waiting for emerging novel therapies, the use of these more established drugs should be considered. Furthermore, one of the advantages of using established immunomodulators is the well-documented knowledge on the long-term side effects and on the mechanisms of action. In this review, the authors discuss 3 well-known immunomodulators that are being applied with increased frequency for the treatment of IBD: tacrolimus, methotrexate, and mycophenolate mofetil. These agents have been used for many years as treatment modalities for immunosuppression after organ transplantation, for the treatment of cancer, and for immunomodulation in several other immune-mediated diseases. First, this review discusses the potential targets for immunomodulating therapies in IBDs. Second, the immunomodulating mechanisms and effects of the 3 immunomodulators are discussed in relationship to these treatment targets.
van Dieren
Jolanda M
JM
Department of Gastroenterology and Hepatology, Division of Gastroenterology and Nutrition, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. j.vandieren@erasmusmc.nl
Kuipers
Ernst J
EJ
Samsom
Janneke N
JN
Nieuwenhuis
Edward E
EE
van der Woude
C Janneke
CJ
D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D008727:Methotrexate / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D011355:Prodrugs; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008727:Methotrexate