Interferon-beta Interferon and glatiramer were the first main disease-modifying therapies introduced for MS following ACTH and corticosteroids. These injectable drugs, which are still used in some cases, modestly alter the natural history relapsing-remitting MS. IFN-β-1b, a nonglycosylated bacterial cell product with an amino acid sequence identical to that of natural IFN-β, was the first of these agents to be tested (Arnason). Several trials showed that the subcutaneous injection of this agent every second day for up to 5 years decreases the frequency and severity of relapses by almost one-third and also the number of new or enlarging lesions (“lesion burden”) in serial MRIs. A large-scale trial (European Study Group, PRISMS Study Group) extended the observations with IFN-β-1b to patients with the secondarily progressive type of MS; progression of the disease was delayed for 9 to 12 months in a study period of 2 to 3 years. The treatment of relapsing–remitting MS with IFN-β-1a in a once weekly intramuscular regimen is similarly effective.
One issue with the longer term administration of interferon is the development of antibodies to the drug. The rate of such antibody emergence increases with the frequency of use of interferon. After a period of years, 30 percent of patients demonstrate antibodies with daily administration, 18 percent with alternate-day use, and less than 5 percent with weekly use. More recent changes in the preparation of interferon have led to reported rates of only 2 percent with antibodies after 1 year of use. There is some evidence that the presence of these antidrug antibodies diminishes the effectiveness of interferon.
Overall, the side effects of the interferon therapies for MS are modest, consisting mainly of flu-like symptoms, sweating, and malaise beginning several hours after the injection and persisting for up to 14 h; they are reduced by preand posttreatment with nonsteroidal anti- inflammatory drugs and tend to abate with continued use of the agents. In severe cases, prednisone 10 mg taken an hour before, and then again after the injection may be effective. Nevertheless, some patients cannot tolerate interferon. A few migraineurs complain of exacerbation of their headaches. There may also be a tendency to depression in susceptible patients treated with interferon, and in our experience, this information, when openly discussed with the patient, often influenced the decision regarding choice of treatment. A rare but notable problem is the induction of a “systemic capillary leak syndrome” in patients with a monoclonal gammopathy who receive interferon. With more than weekly use, there may be an increase in liver function enzymes.
The question of whether to institute disease modifying therapy with an interferon was addressed in the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) study, which examined the effect of interferon (weekly) in patients with a first episode of optic neuritis and at least 2 lesions on MRI that were compatible with MS. Over 3 years, there was a modest reduction in clinical progression or relapse from 37 percent to 28 percent; if further MRI lesions were used as evidence of clinical progression, the difference from placebo treatment was even greater.
Glatiramer Copolymer I (glatiramer acetate), which was synthesized to mimic the actions of MBP, a putative autoantigen in MS, is given daily in subcutaneous doses of 20 mg. Antibodies do not develop to glatiramer, and this has been emphasized as a relative advantage of the drug. Patients receiving glatiramer acetate should be warned of a reaction consisting of flushing, chest tightness, dyspnea, palpitations, and severe anxiety. Injection site reactions occur with both classes of drugs but are rarely troublesome if the sites are rotated. Trials that combine interferon and glatiramer have not produced benefit over either agent alone (Lublin and colleagues).