Immunosuppressive Agents in Multiple Sclerosis

Abstract

Summary:Immunosuppressive agents have been used in multiple sclerosis (MS) for decades. The approval of several immunomodulatory agents against MS beginning in the 1990s, whose putative mechanisms of action appeared "more MSspecific," curtailed the importance of immunosuppressants, which made them treatment options of second choice. However, with the recent approval of mitoxantrone for treatment of patients with active forms of relapsing-remitting or secondary progressive MS and with a number of oral immunosuppressive agents being assessed in phase II and III clinical trials, a "renaissance" of this type of agents is currently occurring. This review provides an outline of the most important clinical studies and discusses relevant side effects of the major immunosuppressants (i.e., mitoxantrone, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, cladribine, and sirolimus/temsirolimus). The current knowledge of the putative mechanisms of action of these compounds is discussed.

Cladribine to treat disease exacerbation after fingolimod discontinuation in progressive multiple sclerosis

“…However, Rituximab remains relatively expensive, and in our healthcare environment (NHS) would have required an individual funding application with (1) potential for delay and (2) likely rejection, based on recent experience. Further alternative DMTs, such as Mitoxantrone and Cyclophosphamide (both off‐label in the UK), carry evidently more significant risks including malignancy and cardiotoxicity 20, 21…”

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

“…Azathioprine (Imuran) is a purine analogue that is metabolized to 6-mercaptopurine and thioinosine acid, which compete with DNA nucleotides, causing immunosuppression [55]. It has found use in autoimmune disorders, such as myasthenia gravis, and to prevent post-transplant organ rejection.…”

“…Methotrexate is a general immunosuppressant that acts primarily by inhibition of dihydrofolate reductase [55].…”

Successful Management of a Neurology Infusion Practice

“…disease progression and relapse rates, 18 its toxicity is significant. 10,15,19,20 There are currently several other targeted monoclonal antibodies-alemtuzumab, rituximab, ocrelizumab, and daclizumab-in clinical development for the treatment of MS. 3,21 If ongoing studies demonstrate clinical benefit, the potential necessity for IV administration of these novel biologic agents is likely to have a significant impact on the management of this disease. 22 The availability of a variety of more effective and more complex infusible agents for the treatment of MS, as well as increased demand for more well-established agents, such as methylprednisolone and IV immunoglobulins (IVIG), has elicited significant interest among neurologists in an in-office integrated infusion center model.…”