May 3, 2000 (San Diego) -- Early and aggressive treatment with an immune-stimulating drug called interferon can delay or possibly even prevent the crippling symptoms of multiple sclerosis (MS), according to findings presented here at the 52nd annual meeting of the American Academy of Neurology. But timing the treatment is crucial, say the European and North American scientists, who gave details of two studies that could teach doctors more about when MS patients will benefit the most from interferon therapy.
MS has at least two phases, says Donald E. Goodkin, MD, medical director of the University of California, San Francisco/Mount Zion MS Center. The first is known as the "relapsing-remitting" (R/R) phase, because it is marked by episodes of flare-ups followed by periods of no or mild symptoms. The R/R phase is thought to be caused by inflammation.
The next phase -- the secondary progressive phase - is marked by a gradual but ongoing breakdown of nerve cells. The inflammation lessens, and another process, as yet unidentified by scientists, seems to cause the disease to worsen. Approximately 50% of people with MS enter the secondary phase within 10 years after the R/R phase begins.
"The suggestion is emerging that interferons target an early step in [disease] development," says Henry F. McFarland, MD, chief of the branch of neuroimmunology at the National Institutes of Health in Bethesda, Md. "We are beginning to define in more detail the type of patient who can benefit most from this treatment."
Both trials described at the conference enrolled patients who were 18-65 years old and were in the secondary progressive phase of MS, Goodkin explains. The main object of both trials was to examine the effect of interferon on the development of symptoms such as paralysis, weakness, and loss of balance or coordination. The investigators also kept watch on secondary factors, called secondary outcomes, such as the number and severity of relapses, how long they lasted, and how often patients were hospitalized.
The two trials had different eligibility requirements. European patients had to have had at least two flare-ups or a gradual progression of disability within the 2 years before the study started. Every other day, they were injected either with interferon or with an inactive substance called a placebo. The North American patients only needed evidence of gradual progression of disability to be eligible. They received a placebo or one of two doses of interferon every other day.
Patients in the European study experienced a significant delay in the progression of their disease, says McFarland. In the North American study, interferon did not slow the progress of the disease, although it did diminish almost every secondary feature studied.
"From that standpoint, the [North American] trial might be considered a failure," says Goodkin. But these findings, he points out, led the investigators to wonder: "Were the North American patients too far advanced to respond to treatment?"
The European patients were younger and at an earlier stage in their disease, says McFarland. Their relapse rates were twice as high as those of their North American counterparts, and they were most likely still in the inflammatory phase of their MS. According to McFarland, this suggests that, to delay disease progression, interferon must be given during the earlier, R/R phase of MS, when inflammation is still active.
However, says Goodkin, "The treatment effect on the secondary outcomes should not be dismissed. I think we can learn a tremendous amount about who the most appropriate patients are for this therapy. I think all of our current treatments work best in the early stages of the disease because they work on the inflammation. If we treat the patient after the inflammatory component of the disease is [no longer] active, interferon will not work."
Unfortunately, other than the suggestion that interferon is best used on patients whose MS it still relatively new, McFarland says his research team has not been able to find a single feature that identifies which patients are most likely to respond. He believes this reflects the complex nature of MS.
"Interferon definitely has an impact on this disease," says Mark S. Freedman, MD, who participated in yet another trial looking at the effects of interferon on patients in the early stages of MS. That study compared two different doses of interferon in 560 patients at 22 centers around the world and showed that the higher doses could slow the progression of MS. However, he says, these studies, which lasted 2-4 years, "are short-term studies in the life of a very chronic disease. Early treatment with the right dose is important. But it's not enough to have a drug that has an effect -- you have to be able to max out that effect."