The findings by principal investigator R. Philip Kinkel, M.D., director of the Multiple Sclerosis Center at Beth Israel Deaconess Medical Center in Boston, are the result of a clinical trial known as Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance (CHAMPIONS), the longest study among MS patients followed from the onset of symptoms. The study was sponsored by Biogen, Inc., maker of Avonex (interferon beta-1a).
"Multiple sclerosis is the most common disabling illness affecting young adults, generally striking between ages 20 and 40," says Kinkel, who is also Associate Professor of Neurology at Harvard Medical School. A chronic disease of the central nervous system, MS affects nearly 1 million individuals worldwide. "Being able to initiate very early treatment could significantly delay the onset of severe neurological symptoms - including loss of vision, mobility and cognitive ability - in this young population."
One of the primary problems in diagnosing multiple sclerosis, explains Kinkel, is that the disease nearly escapes notice in its earliest stages. "The initial symptoms of MS are often non-specific [pins and needles sensations in a limb, electrical sensations, non-specific dizziness or extreme fatigue], suddenly appearing and then disappearing within a short period of time, only to recur and become obvious much later after the disease has already spread throughout the nervous system." To make matters worse, not all patients who experience definite MS-like symptoms from the onset will go on to develop typical MS. Consequently, a second occurrence of MS symptoms involving another part of the nervous system or definite new abnormalities that appear on magnetic resonance imaging (MRI) of the brain and spinal cord are required in order to make a definite MS diagnosis.
This study, involving patients from 32 sites across the U.S. over a five-year period, was designed to determine if much earlier treatment - within a month of the appearance of initial symptoms and before a definite diagnosis had been made - would delay the onset of new neurological symptoms compared to initiation of therapy more than two years after the onset of symptoms.
"The study actually evolved from an earlier investigation, known as the CHAMPS study," explains Kinkel. CHAMPS, a two-year blinded placebo controlled trial in which 383 MS patients were treated weekly with either Avonex or a placebo, found that those individuals who received Avonex experienced a 44 percent decrease in the rate of developing a second MS attack that would qualify them for a diagnosis of MS compared with the patients who received a placebo.
"We were extremely pleased with the outcome of the CHAMPS trial," notes Kinkel. "But we realized that because disabling MS symptoms - such as difficulty walking and thinking that does not improve - may not appear in patients for many years. We would have to conduct a much longer study to determine if Avonex actually slowed the progression of these debilitating symptoms."
To test the medication's long-term effectiveness, the study followed 203 patients, half of whom had been receiving Avonex from the onset of the CHAMPS trial (immediately after demonstrating MS symptoms) and half of whom began treatment with Avonex at a later point, following their second MS attack (or two or more years after their first attack). The study found that patients who began treatment with Avonex immediately after their first attack had a 35 percent reduction in the rate of developing a clinical diagnosis of multiple sclerosis and a 48 percent reduction in the number of relapses when compared to patients who began treatment with a placebo and switched to an active treatment an average of 2 ½ years after the onset of symptoms.
"After five years, our results clearly demonstrated that immediate initiation of Avonex therapy continues to slow the development of clinically definite MS compared to initiation of therapy more than two years after the onset of symptoms," explains Kinkel.
Furthermore, those patients who initiated therapy at the onset were more likely to be classified as clinically stable between years four and five compared with those patients who began therapy more than two years after the onset of symptoms. "Very few patients from either group developed significant disability after five years of observation suggesting that both immediate and early initiation [within two years] of therapy may prevent the development of disability over five years. We plan to follow this group of patients for an additional five years to determine if there is a differential effect on the development of fixed disabilities."
Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, ranking third in National Institutes of Health funding among independent hospitals nationwide. The medical center is clinically affiliated with the Joslin Diabetes Center and is a founding member of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox.