Emerging treatments in multiple sclerosis: azathioprine and mofetil.
Global immunosuppression instead of focused selective or specific immunomodulating strategies may still be relevant in diseases with chronic and broad immune dysregulation such as multiple sclerosis (MS). Among classical or new immunosuppressive drugs, two of them, both inhibiting purine synthesis, show an attractive profile for MS treatment. Azathioprine (AZA) is the most anciently and widely used global immunosuppressive drug in MS. Despite founded initial fears, it can be stated today that AZA is usually well tolerated and compatible with normal daily activities, that it requires minimal monitoring and does not significantly increase the risk of cancer induction after 5 years of continuous usage at the conventional 2.5 mg/kg daily dose. The only two presently available well conducted trials of AZA in ambulatory patients with relapsing-remitting MS show marginally significant beneficial results of AZA treatment on relapse frequency and disability. Some preliminary data on brain MRI are also promising. Mycophenolate mofetil (MMF) affects mainly the desired cell types, with a good safety profile, a rapidly reversible activity, and an absence of mutagenic effect and chromosome breakage. However, it remains to be shown that promising experimental results can be converted into significant clinical results in MS. It is presently demonstrated for AZA and it is presumable for MMF that neither drug is able to cure MS. However, it can be anticipated that either drug in combination with other strategies such as recombinant beta interferon could represent a significant adjunct for the therapeutic control of MS, at least in early ambulatory relapsing-remitting MS. Presently, the choice between the old, no longer 'sexy', but well-known drug as AZA and a young, appealing, but still to be better evaluated drug (notably for the long run) as MMF is a matter of personal, community, industrial and scientific inclination.
Confavreux
C
C
Service de Neurologie, Hôpital de l'Antiquaille, Lyon, France.
Moreau
T
T
D001379:Azathioprine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine