UNIVERSITY OF MARYLAND MEDICAL CENTER: CLICK TO READ MORE"Actions. Interferons (so-called because they "interfere" with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T-cells to pass through.

Specific Interferons Used for MS. Interferon agents used for MS include IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations are urging that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects. [See Table Comparisons between Major MS Agents, below.]

Successes and Drawbacks. The major interferon preparations reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. Studies on their effects on quality of life are limited. In one 2000 study, Avonex reduced the risk for mental impairment by nearly half. Evidence to date does not suggest that interferons can slow progression to any appreciable degree, although studies are ongoing using higher doses and comparisons of all interferons. None of the interferons is a cure, in any case, and when the agent is discontinued, disease activity may increase.

Side Effects and Complications. Side effects include the following:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first six months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after two or three months.
Depression. Interferon has been associated with depression during the first two to six months following initial therapy. Recent studies have suggested, however, that there is no greater risk for depression in patients taking any of these agents. More work is needed, however, to determine if specific patients may be at higher risk than others for depression with these drugs. MS itself, in any case, is highly associated with depression.
Over time, people taking the interferons develop antibodies to the drugs that neutralize their effects. The risk is highest in Betaseron and lowest in Avonex. Patients who experience this, however, often can be effectively treated with the alternative interferon. In addition, in many cases, the antibody levels decline and the patient may be able to take the same interferon.

Comparisons between Major MS Agents


Comparison Items

Betaseron (IFN1b)

Avonex (IFN1a)

Rebif (IFN1a)

Glatiramer acetate (Copazone)

Injection Timing

Every other day.

Administered weekly by injection.

Three times a week.

Daily injections.

Pain at Injection Site

Severe pain and injury at injection site.

Less pain than Betaseron and very little injury.

Less pain than Betaseron but more than Avonex.

Some pain at injection site. It has less severe side effects than the interferons, however.

Effect on Early MS and Relapsing-Remitting MS

Reduces frequency of relapse by about 30%. Advocates of Betaseron argue that it has demonstrated a more significant effect on reducing lesions and relapse rates than Avonex after two years.

Reduces lesions and relapse rates. Long term use may slow progression. It may delay development of MS in patients with a first MS event, although significance unclear. Has beneficial effects on mental function.

Has impact on all major aspects of relapsing-remitting MS. It was more effective than Avonex in a 2002 study. (The drugs are identical, but Rebif is given more frequently.)

Glatiramer equal to Betaseron in effectiveness.

Significantly reduces relapse rates and lesions and, according to a six-year study, the longer it is taken the better the effects.

Effect on Secondary or Primary Progressive MS

A major 2001 study reported significant reductions in progression in patients with secondary progressive MS.

A 2002 study of secondary progressive MS reported reduction in lesions, fewer relapses, and improved quality of life. (Did not appear to have any effect on disability.)

Not yet known. Early studies reported fewer lesions, fewer relapses, but no affect on disability.

The drug does not appear to stop progression of MS, and, so far, it has little effect on chronic-progressive MS. Studies suggest is has properties that protect nerve cells.

Development of antibodies that neutralize the drug's effect

Within three years, between 25% and 40% of patients develop antibodies to Betaseron. In a 2002 comparative study, Betaseron produced the highest incidences of antibodies, compared to the other beta interferons.

Less risk than in Betaseron and Rebif. Studies report a risk of less than 5%.

Less risk than with Betaseron (18.7% in one study).

No risk.

Glatiramer Acetate

Glatiramer acetate (Copaxone) formerly called Cop-1 or copolymer-1, is a synthetic molecule created to resemble a basic protein found in myelin. It is being used as a decoy to trick white blood cells into attacking it instead of myelin. Studies indicate that relapse rates for patients using glatiramer can be reduced by 30% to 72%. Benefits have persisted for at least six years. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heart beat, flushing, anxiety, and shortness of breath. [See Table Comparisons between Major MS Agents.]

Corticosteroids

Actions. Corticosteroids reduce inflammation in the central nervous system (CNS) and may help suppress the immune system's attack on myelin and even improve electrical conduction. Although they are very useful for improving acute symptoms in the relapsing-remitting patient, steroids do not improve the long-term course of the disease and can lose effectiveness if over-used. Physicians generally restrict the use of steroids to severe attacks when the patient's ability to function is severely limited. There is no consensus, however, on the best form, dose, route, or duration of steroid treatment.

Specific Agents. High-dose methylprednisolone given intravenously is typically administered for major relapse, and oral prednisone is given for mild to moderate relapses. In one study, the use of high-dose intravenous methylprednisolone followed by oral prednisone delayed the development of MS in patients with early symptoms (optic neuritis). Studies are underway using pulsed doses of intravenous methylprednisolone on a regular but periodic basis to determine if it will slow progression in patients with secondary progressive multiple sclerosis. A 2001 study on patients with relapsing-remitting disease indicated that it might slow brain changes.

It should be noted that oral prednisone used alone may actually exacerbate optic neuritis, the swelling of the nerves of the eye, so this drug is now rarely prescribed during flare-ups.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system can be particular problems for MS patients; they include sleeplessness, memory loss, anxiety, and depression. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Intravenous Immunoglobulin

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. In one two-year study, 31% of treated relapsing-remitting patients improved, 16% had worse symptoms, and 50% were unaffected. Experts are not yet sure why this treatment works. In any case it does appear to slow progression and it is extremely expensive."