Perhaps the most effective treatments currently available today deal with the autoimmune component of MS and work by regulating aspects of the immune system. Avonex®, Betaseron®, Copaxone®, and
Rebif® have been approved to modify the disease in relapsing forms of MS; Betaseron® has been FDA-approved for use in people who have SPMS. Avonex® is being used for worsening MS in people presenting with a clinically isolated syndrome (CIS): one neurologic attack with MRI evidence of demyeli-nation. A fifth drug, Novantrone® (mitox-antrone), has become available during the past few years for worsening multiple sclerosis. The interferons and Copaxone® are given by self-injection; Novantrone® is administered intravenously by nurses (or your physician).
Interferon Beta Type I Beta interferon (IFN-b) comes in two preparations: interferon beta-1a (Avonex® and Rebif®) and interferon beta-1b (Betaseron® in the U.S. and Betaferon® in Europe). Beta interferon is a naturally occurring biochemical in the human body and belongs to a group of biochemicals known as interferons (IFNs), which regulate the functioning of the immune system. The mechanism by which IFN-b functions is complex and not fully understood.
Beta interferon reduces the levels of another interferon, called interferon gamma (IFN-g), which is known to be associated with activating the disease process in MS. It appears to block certain white blood cells from attacking the myelin covering of the nerves in the brain and spinal cord. It also seems to stop a type of white blood cell, called a T cell, from releasing immune system signaling molecules (that would otherwise encourage inflammation). It also seems to interfere with the process of summoning new immune system cells to the site of inflammation.
All interferons can be self-administered: Betaseron® subcutaneously (under the skin) every other day; Rebif® subcutaneously three times a week; and Avonex® intramuscularly (into the muscle) once a week.
We know that MS is a very unpredictable disease and none of us knows what disease course a person will have from the outset. Based on the newest MS research, thought leaders believe that early treatment is extremely important. If MS continues to progress while you are using IFN-b, that doesn't mean the drug isn't working—it might have progressed faster if you hadn't been using it. In fact, studies imply this.
When research shows a benefit in the burden of new lesions shown on MRI between the people being treated with IFN-b as compared to a placebo group (those not receiving the drug) over the same period, it is very hard to tell whether it has worked fully for some people, partially for others, and not at all for the rest. This is because no one has any idea of what would have happened to any particular person without the drug. Unless the studies are extremely large, all that can be said is that the drug reduces lesion load (changes seen on MRI demonstrating loss of healthy tissue in the brain, spinal cord, or both) by an average over a certain period of time.
The interferons may not work for everyone and, indeed, some people seem to do very well with them whereas others do not. Research is currently underway to enable clinicians to predict "responders" versus "nonresponders" to treatment.
What IFN-b is not, is a cure for some people and not at all effective for others. The bottom line is that, even if it doesn't appear to be fully working for you, it may very well be helping modulate your disease.
The principle side effects of IFN-b use are flu-like symptoms—fever, night sweats, and muscle aches. These can be very unpleasant, but often subside after a few months and respond well to nonsteroidal medications such as ibuprofen, acetaminophen (Tylenol) or even low-dose steroids. Slowly increasing the dose (dose titration)
has also been shown to be effective in reducing this side effect.
Liver toxicity (effect on blood liver function) has been noted in some patients, particularly at higher doses, although this problem is usually mild. Be sure to notify your doctor if you are experiencing new symptoms, whether they appear to be attributable to MS.
Depression has been described as another potential side effect and should be addressed by your healthcare team before you start interferon therapy.
Injection site reactions can also be a problem, and it is essential to rotate the injection site to reduce these. Briefly numbing the skin at the injection site with ice or anesthetic cream, site rotation, getting the drug to room temperature before injecting, and taking antihistamines before injecting may help. One of the difficulties many people face is having to inject themselves. Autoinjectors are available with Betaseron® and Rebif®. If injection becomes too great a challenge, people confronting this difficulty are advised to enlist an injection partner. Most people get over this "needle phobia" eventually with the proper support.
In one study in Europe, IFN-b was shown to reduce the relapse rate in SPMS by a statistically significant amount. However, two other similar studies failed to show statistically significant effects. It is known that relapse rate falls off during the course of the disease and that inflammatory activity is correlated with relapses. It is also believed that the mechanism of disease activity changes from an inflammatory one to a neurodegen-erative one during the secondary progressive phase of the disease (SPMS). Based on these and other results, it seems likely that IFN-b is only effective at preventing inflammation and relapses and not effective in people with progressive courses without relapses.
Copaxone®, or glatiramer acetate, is a collection of synthetic peptide derivatives—the building blocks of protein—that are believed to work by modifying the body's immune response to myelin. As with IFN-b, its method of action is complex and is not fully understood. One theory proposes that, by flooding the body with the substances similar to those in proteins found in the myelin sheath, the drug acts as a decoy and draws some of the attack away from the brain and spinal cord.
Copaxone® is about equally effective as IFN-b in reducing relapses and MRI changes. It is injected subcutaneously on a daily basis. The most common problem that users have are injection site reactions that include itching and inflammation. These reactions can be alleviated by site rotation and by ensuring that the drug is at room temperature before injecting it. An autoin-jector is available for administrating Copaxone®. Copaxone® comes in a prefilled syringe, as does Rebif® and Betaseron®. Avonex® is available as a prefilled product or one may prefer to reconstitute the powder and liquid. Betaseron® is available with a prefilled liquid (diluent) that is mixed with the powder.
A systemic reaction may rarely occur with Copaxone® involving flushing, chest and joint pains, weakness, nausea, anxiety, and muscle stiffness. This reaction tends to resolve after about a quarter of an hour without any treatment.
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