Promising Data from Study Suggests Patients at High Risk for Developing Multiple Sclerosis can Significantly Delay Progression to Clinically Definite MS
This report was reviewed for medical and scientific accuracy by William H. Stuart, MD , Director,Multiple Sclerosis Center of the Shepherd Center, Founding Partner Peachtree Neurological Clinic, Medical Director for Rehabilitation Services, Piedmont Hospital, Atlanta,GA; Chairman, HealthMed Advisory Board, webhealthsearch.com .
People who experience a "demyelinating" event (such as optic nerve inflammation or a spinal cord attack resulting in profound limb weakness) live in fear of a second occurrence. When that happens, perhaps months or years down the line, it conclusively signals a diagnosis of multiple sclerosis (MS).
Now, data from a new clinical study suggests that the drug Avonex® (Interferon beta-1a), when given after that first demyelinating event, may delay the progression to clinically definite MS.
The study, known as CHAMPS (which stands for Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study), included 383 patients in the United States and Canada who were at high risk for developing this potentially debilitating disease.
Patients in the study were classified as "high risk," meaning they met two criteria. First, they had experienced a single, isolated neurologic episode that doctors thought was suggestive of MS (inflammation of the optic nerve, coordination problems, double vision, limb weakness, or bowel and bladder problems). They had also received an abnormal MRI brain scan revealing lesions typically found on the brains of MS patients.
Participants in CHAMPS received treatment of once-a-week injections of either Avonex® or placebo for up to three years.
The exact results of the study will not be released until later in the year 2000. The early indication is that the results are very promising. The progression to clinically definite MS was significantly longer among patients treated with Avonex® compared to those patients treated with placebo.
In fact, the recommendation of an independent board of neurologists and statisticians was to discontinue the trial. Biogen, the manufacturer of Avonex®, then stopped the clinical trial so the research data could be submitted to the US Food and Drug Administration as quickly as possible.
"This is a clear demonstration that a therapeutic intervention can be effective in delaying the onset of clinically definite MS in high-risk individuals," said Jim Vincent, chairman and CEO of Biogen.
Evidence of Delayed Onset is Encouraging
Avonex® will not provide a cure for those patients suffering with MS. However, the finding that Interferon beta-1a may slow progression to the clinically definite stage fits right in with an important trend: doctors are prescribing disease-modifying agents as soon as possible so their patients can stay functional longer.
Studies suggest that by starting treatment early, the progression of MS can be slowed or even halted. This has been acknowledged by the US National Multiple Sclerosis Society, which has issued "treat early" guidelines regarding the disease-modifying agents Avonex®, Betaseron®, and Copaxone®. The guidelines state, "initiation of therapy is advised as soon as possible following a definite diagnosis of MS and determination of a relapsing course."
As a result, doctors who specialize in MS are becoming more aggressive in early diagnosis and treatment with these drugs, which act on the immune system. Using drugs like these is important because MS is likely caused by the destruction of myelin by the immune system. Myelin is a fatty tissue surrounding and protecting nerve fibers; this "insulation" helps nerve impulses flow to and from the brain. Therefore, a demyelinating event occurs when the myelin sheath of a nerve fiber is somehow removed or destroyed. Researchers believe that Avonex® works by regulating the immune system's reaction against myelin.
Avonex® is a form of interferon, which is a naturally occurring protein that helps regulate the immune system and ward off disease. Not all interferons are exactly the same. For example, Avonex® has the same arrangement of amino acids as occurs naturally in the human body, while Betaseron® has a slightly different composition. Avonex® is given once a week intramuscularly, while Betaseron® is administered subcutaneously every other day.
In a major clinical study, Avonex® was found safe and effective in treating patients with relapsing MS. The study included 158 people treated with Interferon beta-1a for up to two years and an additional 143 people treated with placebo. Avonex® reduced the risk of disability progression by 37% compared with placebo, and helped patients keep their existing function levels for a longer period of time.
The study also found that Avonex® recipients were less likely to become severely disabled, and fewer needed canes or crutches for walking. Flare-ups were less frequent in the Avonex® group as a whole, compared with the placebo control group.
New Hope for Patients at High Risk for Developing Clinically Definite Multiple Sclerosis
CHAMPS patients were at high risk for developing clinically definite MS, but were not necessarily high-risk patients (i.e., having an aggressive or severe case of MS). For relapsing MS, once-weekly injections of Avonex® are typically given by a physician. Other patients may have the option of having a friend or family member administer their injections.
Most patients tolerate Avonex® therapy well. However, just like any prescription drug, there may be side effects. Flu-like symptoms can occur early on in therapy; they tend to disappear within a day of the injection, and occur less frequently with subsequent injections. In any case, flu-like symptoms can be easily managed with acetaminophen (such as Tylenol brand) or by timing the weekly injection in the evening, so the first few hours of side effects will occur while the patient is asleep.
Clinical trial data suggests headache, weakness, and pain can also occur-though the frequency is not statistically different than what is reported by patients who are taking placebo instead of Avonex®. Incidence of depression was not greater among people receiving Avonex®. Depression is a symptom of MS and is also associated with interferon treatment.
People at high risk of developing MS should stay tuned for new developments. Biogen officials say they plan to work closely with the FDA to review the CHAMPS data on the use of Avonex® in people who have had a demyelinating event and have shown apparent lesions on a MRI brain scan. In fact, the company plans to file applications with regulatory agencies worldwide for a broadened prescribing label.
Until then, a doctor should decide the course of action, after consulting the patient and the patient's healthcare providers. Neurologists specializing in MS can best decide the appropriate treatment for patients at high risk of developing this debilitating disease.