Pros and cons of starting multiple sclerosis treatment early

An editorial accompanying a published debate on the pros and cons of starting treatment early in the course of multiple sclerosis comes down in favor of early treatment for this potentially devastating disease.

This opinion coincides with a consensus paper published by the National MS Society.

The April issue of the Archives of Neurology features both sides of this debate on early treatment for MS.

Background: Currently five therapies are approved by the U.S. Food and Drug Administration for the treatment of multiple sclerosis. These agents can reduce future disease activity for many individuals with relapsing forms of MS, including those with secondary progressive disease who continue to have relapses. The National MS Society's Medical Advisory Board recommends that initiating MS therapy with an immunomodulating drug (such as FDA-approved interferons or glatiramer acetate) should be considered as soon as possible following a definite diagnosis of MS with a relapsing course, and for selected patients with a first attack who are at high risk for MS. Some clinicians disagree, however, choosing to defer treatment until the extent of disease activity is more clearly established.

The Debate: E. M. Frohman, MD, PhD (University of Texas Southwestern Medical Center at Dallas) and an international panel of coauthors present the following arguments in favor of early treatment in an article titled, "Most Patients with Multiple Sclerosis or a Clinically Isolated Demyelinating Syndrome Should Be Treated at the Time of Diagnosis" (Archive of Neurology 2006;63:614-619):

• Most who have MS will develop significant disability over time, and when MS is initially diagnosed, it is impossible to determine whether its course will be disabling or benign (mild course of disease).
• Studies show that injury to nerve fibers - which leads to the progression of disability that can occur in people with MS - begins early in the course of the disease. Even if a person appears to be doing well, with few clinical relapses, there may be evidence on MRI of tissue damage and loss that is associated with eventual disability.
• The approved agents decrease the number and severity of relapses, the number and size of new lesions (areas of damage to nerve-insulating myelin), and progression of disability. These treatments work best early in the course of MS, and do not work as well during progressive stages.
• Delaying treatment has been associated with more progression of disability and a larger volume of disease damage as seen on MRI.

The authors conclude that, given that therapies can significantly reduce MS disease activity, then "almost every" patient early in the course of MS should be offered disease-modifying therapy.

On the other hand, Sean J. Pittock, MD, and colleagues (Mayo Clinic, Rochester, MN) cite the reasons for delaying treatment until the course of MS becomes more apparent in an article titled, "Not Every Patient with Multiple Sclerosis Should Be Treated at Time of Diagnosis" (Archives of Neurology 2006;63:611-614):

• If left untreated, MS often runs a "favorable" course, but it becomes difficult to distinguish a favorable course from treatment success if people are treated for a long time.
• The approved treatments are only partially effective in the short-term; it has not been proven that they can prevent long-term disability.
• Drawbacks to treatment include the cost, adverse effects, neutralizing antibodies (immune system proteins that can interfere with the effectiveness of interferons), and some patients' reluctance to make a long-term commitment to taking injected medications.

The authors suggest that monitoring people with MS regularly with clinical examinations and MRI scans may help to identify people whose course requires treatment with disease-modifying therapies. They conclude that well-designed studies are required to determine whether early, versus delayed, treatment of relapsing MS makes a clinically meaningful difference in terms of the development of disability.

In an accompanying editorial, E. S. Roach, MD (Wake Forest University School of Medicine, Winston-Salem, NC) comments on the two reports and concludes in favor of early treatment (Archives of Neurology 2006;63:619).

"One approach, as proposed by Pittock and colleagues, is to defer treatment until the patient's course is better established, possibly allowing those with less aggressive disease to avoid years of unnecessary treatment," comments Dr. Roach. "But as Frohman and colleagues counter, most people with newly diagnosed MS do progress, and we must consider that treatment could be less effective if started later in the course of the illness."

Dr. Roach notes the necessity for finding specific evidence that some people do not need treatment. "Without such evidence for individuals with MS, it will be difficult to know for sure whether it is ever safe to defer treatment," he concludes. "While it would be wonderful if we could avoid treating some patients with MS, until we can distinguish these individuals from the others, it is probably better to offer treatment to all patients except in the setting of a clinical trial."