Therapy of rheumatoid arthritis with mycophenolate mofetil

Abstract

Mycophenolate mofetil, a pro-drug for mycophenolic acid, is an investigational immunosuppressive compound that is being developed for the treatment of rheumatoid arthritis (RA). The drug and its primary metabolite, mycophenolic acid, inhibit the de novo pathway of purine biosynthesis and have greater anti-proliferative effects on lymphocytes than on other rapidly dividing cells. Significant clinical improvement has been seen in many mycophenolate mofetil-treated RA patients who have been refractory to treatment with a variety of disease-modifying anti-rheumatic drugs (DMARDs). Treatment with mycophenolate mofetil reduces rheumatoid factor titres, immunoglobulin (IgG, IgM, and IgA) levels, and the total number of T cells (CD2) in RA patient peripheral blood; in addition, lymphocyte mitogen responses are inhibited and delayed hypersensitivity skin test reactivity is decreased. A dose of 2 g daily is more effective than lower doses, including several pulsing regimens. The most frequent adverse events reported by patients on mycophenolate mofetil are gastrointestinal, mainly nausea, vomiting, abdominal pain, and diarrhea. RA studies have demonstrated no clinically significant nephrotoxicity, hepatotoxicity, or bone marrow toxicity attributable to mycophenolate mofetil.