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TREATING MS EARLY REDUCES RISK OF SECOND EXACERBATIONS

SAN DIEGO—A new international, randomized study suggests that treating individuals at high risk for multiple sclerosis with interferon beta-1b before they show commonly accepted diagnostic criteria decreases the risk for disease progression during the next two years.

“By treating the patients with high-dose, high-frequency interferon beta-1b (Betaseron), we reduced their risk of a second attack or MRI progression by 50 percent,” said Paul Freedman, MD, Professor of Medicine (Neurology) at the University of Ottawa in Ontario, Canada.

In the study, 176 patients were assigned to placebo and 292 patients received interferon beta-1b in a 5:3 ratio: at the end of two years, 45 percent of the placebo group and 28 percent of treated patients had a second exacerbation, a significant difference (p<.0001), Dr. Freedman reported here in a press briefing at the AAN Annual Meeting.

In addition, 85 percent of the placebo group and 69 percent of treated patients had MRI changes after two years, showing disease progression, he said. That difference was a 46 percent relative risk reduction, which was significant (p<.00001), he said.

The study, sponsored by Schering AG of Germany, a marketer of interferon beta-1b, was designed to determine whether treating earlier with interferon was beneficial.

THE MCDONALD CRITERIA

Dr. Freedman said: “There has always been some controversy as to whether these patients should be treated. By the McDonald Criteria definition, they have not yet met criteria for multiple sclerosis. There has been skepticism about the McDonald Criteria not being specific enough to warrant treatment.”

An international panel headed by W. Ian McDonald, PhD, of London's Institute of Neurology developed the McDonald Criteria for Diagnosis in 2001. The criteria require two or more attacks as well as objective clinical evidence of two or more lesions on the MRI. (See www.mult-sclerosis.org/DiagnosticCriteria.html for more on the McDonald Criteria for MS Diagnosis.)

“We used McDonald criteria as an endpoint,” Dr. Freedman said, enrolling patients with a wide spectrum of first demyelinating events. “We tried to be inclusive and representative of the patient world as we see it today,” he said. Other studies selected other types of patients for entry. We were looking across the board at all these patients.

“The first thing we noticed, irrespective of treatment, is that if we followed the patients both clinically and by MRI within six months, 50 percent met McDonald criteria so they actually did have multiple sclerosis; 85 percent met criteria by two years.”

He said the study showed that if a patient seems to have multiple sclerosis on the basis of the first clinical attack, it is highly likely that the suspicion of multiple sclerosis is accurate.

Dr. Freedman said that investigators were seeking study subjects who had one clinical attack and then two brain lesions that were not apparently related to the clinical symptom. “If they had optic neuritis, the attack was hitting the optic nerve, so they had to show at least two lesions in the brain but not on the optic nerve,” he explained. “If the manifestation was a spinal cord syndrome, they had to have two lesions outside the spinal cord, giving some indication of dissemination.”

When those lesions occurred – before, after, or during the attack of optic neuritis – cannot be determined. “We can't date those lesions,” he said. “The most important aspect is that it is multiple. Multiple sclerosis implies dissemination throughout the CNS.”

OTHER PATIENTS TO TREAT

Dr. Freedman said that while the patients he treated make up the earliest group treated for suspected multiple sclerosis; there is actually another group with earlier disease that might also be tested. We see lots of patients in our clinics, young and old, who have never had a history of an event, who have absolutely pristine neurological examinations, but a head MRI shows a bunch of little white spots or unidentified bright objects, or UBOs.

“What are they? Are they at risk of developing the disease? Is it inconsequential?” he asked. “We used to think that a clinically isolated syndrome was the first clinical stage, but maybe there is a preclinical stage and there are other signs in that population that would be helpful in identifying those who are even more at risk.”

EARLY TREATMENT IS CRITICAL, EXPERTS SAY

“Most of us who treat people with multiple sclerosis felt that clinically isolated syndromes were, in fact, an early form of multiple sclerosis,” said Rhonda Voskuhl, MD, Associate Professor of Neurology at the University of California-Los Angeles (UCLA). “Generally, we think that the earlier the treatment in multiple sclerosis the better off the patient will be.”

“Earlier is better” for treatment, agreed her UCLA colleague, Nancy Sicotte, MD, Assistant Professor in Residence. “However, I think the results achieved in this trial are not as robust as I would have thought.”

Dr. Freedman said that 95 percent of the patients in the study – both placebo and experimental groups – agreed to remain in an extension study for five years, with results possibly being reported by 2008.

The most relevant factor that clinicians want to know is: “Yes, it made a difference in year one. Yes, it made a difference in year two. But is it going to make a difference five years down the road?” Dr. Freedman asked. “That would really mean we should start therapy early.”

ARTICLE IN BRIEF

  • ✓ A new study reports that treating individuals at high risk for multiple sclerosis with interferon beta-1b before they show commonly accepted diagnostic criteria decreases the risk for disease progression during the next two years.