Lectures: Treatment Options - Standard Therapy
Treatment of Relapses
Immunosuppression with steroids or corticotropin (ACTH) has been used for many years for treatment of exacerbations of MS. Historically, ACTH was the first immunosuppressant given to MS patients with some benefit. Currently, corticotropins are largely surpassed by other steroids, especially Prednisone and Methyl prednisone. Both ACTH and steroidal medications can suppress cell-mediated immunity and as well as humoral immune response to some degree. The most important effect, however, is a marked suppression of inflammatory response to any inciting event, including immunologic reactivity. Both medications have been shown to decrease the severity and duration of exacerbations in MS. Recent research has shown that corticosteroids may also improve the blood brain barrier leakage and thus inhibit the entire inflammatory demyelinating process.
Oral Prednisone is often used for mild to moderate exacerbations of MS. Large doses of oral steroids appear to reduce the length of a MS attack. There is no standard regimen for this treatment: a commonly recommended dose is 1mg/kg of patient's weight per day, but duration of treatment and taper plans may vary. However, steroid treatment should not be continued until a precipitating abnormality resolves, because unfortunately this may never happen.
Solu-Medrol (Methylprednisone) is often used for treatment of severe exacerbations. Typical doses range from 500 to 1000 mg/day for 3 to 5 days. This medication is administered intravenously and can be followed by an oral Prednisone taper.
Severe bouts of optic neuritis with significant loss of vision are often combated with IV steroids with favorable outcome. Doses of medications are similar to the ones used for severe exacerbations of MS.
Complications of steroid treatment may include nonspecific immunosupression leading to opportunistic infections, fluid retention, hyperglycemia, hypokalemia, behavioral disturbances, peptic ulcers, osteoporosis, hypertension and increased risk of cataract development. Supplementation of steroid therapy with H-2 blockers, Potassium and vitamin D with calcium is frequently useful to reduce side-effects. Avoidance of salt or sugar during steroid therapy is recommended.
Prevention of Relapses
Two recombinant interferon-ß's have been approved for treatments of patients with MS who have a relapsing-remitting course of the disease - Interferonß-1b and Interferonß-1a. A controlled double-blind study that lasted for over 2 years established that Interferonß-1b (Betaseron) is effective in relapsing-remitting patients. This medication is administered by subcutaneous injections QOD. It reduces the number of exacerbations by 30% per year per patient, and the severity of relapses that do occur is also reduced. An MRI study revealed fewer lesions in the treated group versus the placebo group. Patients with the stable or progressive course of the disease are not yet known to benefit from this treatment. This medication can exhibit significant side effects that may require discontinuation of treatment. All patients experience local injection site reaction. Some patients even developed tissue necrosis at injection site. Many patients complain of flu-like symptoms following the injection, including chills and fevers, myalgia and malaise. Blood levels need to be monitored while on this medication to assess liver function and WBC count. Liver function abnormalities and leukopenia were seen in some patients. Interferon-1a (Avonex) is now also available for clinical use. Preliminary results of clinical trials suggest that this medication is very similar to Betaseron in its positive effects on the relapsing-remitting population of patients. It appears to reduce the likelihood of progression of the early disease. Avonex is claimed to have fewer side effects than Betaseron (i.e.,. Significantly reduced risk of injection site reaction), but more thorough and broad clinical experience is needed to confirm this. Interferonß-1a (Avonex) is administered by the intramuscular injections once per week.
Interferons in general and ß-interferons in particular are glycoproteins with known antiviral activities. Beta-interferon regulates expression of MHC class II molecules and thus interferes with the interaction of the trimolecular complex (discussed earlier). The net result is prevention of T cells activation that accounts for a decrease in the relapse rate. Other immunomodulating medications await FDA approval for use in patients (see "Medications on the Horizon" chapter).