Teriflunomide is an oral drug that suppresses the immune system by inhibiting dihydro-orotate dehydrogenase and suppressing synthesis of DNA pyrimidine bases. In the TEMSO trial, the drug demonstrated a 31 percent reduction in annualized risk of relapse and 30 percent reduction in risk of disability progression (O’Connor and colleagues, 2011). Reported serious adverse effects included nasopharyngitis, diarrhea, transaminitis, and hair thinning. It is considered teratogenic (pregnancy category 4) and cannot be used in individuals considering pregnancy.
Other immunosuppressive drugs for MS Drugs such as azathioprine and cyclophosphamide, as well as total lymphoid irradiation and bone marrow transplantation, have been given to small groups of patients and seem to have improved the clinical course of some (Aimard et al; Hauser et al, 1983; Cook et al). However, the risks of prolonged use of immunosuppressive drugs, including a chance of neoplastic change and infection, typically preclude their widespread use. The study by the British and Dutch
Multiple Sclerosis Azathioprine Trial Group attributed no significant advantage to treatment with this drug.
For the chronic, progressive phase of the disease, an MS study group reported a modest delay in the advance of the disease after a 2-year trial of prednisolone and cyclophosphamide, but also noted the potentially serious toxicity associated with this approach. At least one subsequent blinded, placebo-controlled study with cyclophosphamide has failed to show any benefit but many groups continue to use it for recalcitrant and severe acute cases. In one trial involving patients with chronic progressive MS, weekly low-dose oral methotrexate resulted in slight improvement difference and produced some reduction in the volume of cerebral lesions on the MRI compared with control cases (Goodkin et al, 1996). Because this regimen is well tolerated, it may still have some occasional use. Among these more aggressive agents, mitoxantrone, a drug with broad immunosuppressant and cytotoxic activity, at one time attracted interest but was limited by cardiotoxicity (Hartung et al). Mycophenolate and similar drugs have been tried with varying success.
General Measures in the Treatment of MS
Fatigue, a common complaint of MS patients, particularly in relation to acute attacks, responds to some extent to amantadine (100 mg morning and noon), modafinil (200 to 400 mg/d), pemoline (20 to 75 mg each morning), methylphenidate, or dextroamphetamine. For depression associated with the disease, there does not seem to be any superior antidepressant and donepezil has not been found to be helpful for cognitive problems.
Agents such as 4-aminopyridine improve conduction through demyelinated central nerve fibers by blocking potassium channels. In some patients these drugs have shown measureable improvements in gait. They are pro-convulsant and should be avoided in individuals at risk of seizures.