By Cameron Johnston
Special to DG News
LAUSANNE, SWITZERLAND -- March 24, 2000 -- An international trial with the beta-1 inteferon drug, Rebif (Ares-Serono International SA), seems to indicate that the beneficial effect of the drug in treating relapsing remitting multiple sclerosis may last for four years or more without weakening.
"A four-year study in a chronic disease might seem short, but it's way longer than anything there is out there," said Dr. George Rice, a professor in the department of clinical neurological sciences at the University of Western Ontario, in London, Canada and one of the investigators on the study.
The study results were presented March 23 at the European Charcot Foundation Symposium, in Lausanne, Switzerland (ECFS).
The study was conducted as an extension to the PRISMS (Prevention of Relapses and Disability by Interferon beta-1, Subcutaneously in Multiple Sclerosis) trial. That study, which was published in The Lancet in 1998, showed that subcutaneous injections of Rebif, either 22 mcg or 44 mcg three times per week over a two year period, resulted in significant reductions in the number of brain lesions visible on MRI scan. That study also showed significant reductions in the length of time that passed before the patient progressed to his or her first relapse, and again the length of time before experiencing a second relapse.
Relapsing-remitting MS, as the name suggests, is characterized by periodic exacerbations of symptoms, averaging approximately one relapse per year for most patients. The number of acute attacks a person suffers in a year could be the single most important predictor of the long-term outcome of the disease. Although it has not been proven conclusively, the evidence seems to suggest that by preventing the number of MS lesions that show on MRI examination, later disability could be prevented.
The latest analysis of the PRISMS trial, which involved 447 of the original 560 patients, produced several interesting and clinically important findings. First, there was an 80 percent reduction in the number of lesions in the brain and on the spinal cord among those taking the higher dose of Rebif (44 mcg) as compared to those taking the placebo. This reduction is actually more convincing than the fact that there was a 30 percent reduction in all attacks and 50 percent reduction in severe clinical attacks because it means the drug is working on the underlying, silent indicators of the disease process, Dr. Rice explained in an interview with Doctor's Guide.
"We're grateful to knock out a third or half of the bad attacks a patients might be expected to experience, but if we can knock out 80 percent of the smoldering lesions of inflammation in MS, it's a tremendous advance."
It was also found that the length of time required for a patient to show a one-point change on the Extended Disability Symptom Score (EDSS) was double for those taking the higher dose. The EDSS measures symptom severity - the higher the number, the worse the patient's condition. "This gives the patient much more staying time at their present level of functioning," Dr. Rice said.
A third important finding is that patients who took the drug for four years did not develop neutralizing antibodies, which usually occur in 20-30 percent of all patients who take interferons and which result in a wearing off of the drug's beneficial effect. Nor were there signs of the patients developing brain atrophy or shrinkage, although Dr. Rice attributes this, in part, to the fact that there were fewer brain lesions and fewer acute attacks of the disease.
"Until patients have anything better, they are better off sticking with
higher-dose interferons," Dr. Rice said. "Higher doses are better and are
less likely to be encumbered by neutralizing antibodies."