When Should a Patient With MS Switch Therapies?

The Expanded Disability Status Scale (EDSS) helps quantify the results of a standard neurologic exam, but “it’s fairly insensitive to change, and there’s a 25% examiner variability issue,” said Mark Gudesblatt, MD, Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Patchogue, New York. “The EDSS was invented by John Kurtzke 50 years ago,” he added. “What other technology has been unchanged for 50 years and remains the mainstay for clinical trials and patient care?”

Another concern is that, particularly in the early course of MS, “a fair amount of damage can accumulate, as evidenced by MRI, and not be apparent clinically, either to the patient or to the physician,” said Dr. Cohen.

In addition, the neurologic exam often does not measure cognition, which greatly influences a patient’s quality of life. But neurologists can incorporate a cognitive exam into an office visit by testing patients’ memory, reaction speed, and general awareness, said Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center. Neurologists also can administer the Symbol Digit Modalities test, which is “the most sensitive single test for measuring cognitive decline in MS,” he added.

Is Help on the Way?
Because of the difficulty of conducting placebo-controlled trials, future drug studies are likely to include active comparators, said Dr. Lublin. The resulting comparative efficacy data will greatly help neurologists make treatment decisions. Studies comparing one highly active agent with another are unlikely to be performed, but comparisons of new products with older therapies probably will be published. “Alemtuzumab’s whole development program, practically, was against interferon,” and it has provided useful information, said Dr. Lublin.

The current emphasis on personalized medicine has raised questions about whether an individual patient may respond better to one agent than to another agent. “We hope to be able to get this kind of information in the not-too-distant future by using biomarkers of responsiveness,” said Dr. Lublin. Trials of daclizumab provided evidence that patients likely to respond to the drug had an immunologic biomarker. “It’s an interesting and exciting area for the future—and hopefully not-too-distant future,” said Dr. Lublin.

For the moment, individual clinical judgment remains the basis for decisions about patients’ drug regimens. “It’s a matter of trying to figure out the threshold of [disease] activity that would justify switching,” said Dr. Lublin. “None of these therapies is perfect. People have had attacks and changes on their MRI with every one of the therapies that we have. And so it becomes rather individualized as to what you think is best for the patient.”

When considering whether to change a patient’s drug regimen, neurologists should first consider the number and severity of the patient’s relapses and how well he or she has recovered from them. The neurologist also should look for the accumulation of neurologic impairment, which could indicate incomplete recovery from relapses or a transition to progressive disease. The physician should ask the patient how his or her life is going and watch for symptoms of depression, fatigue, and cognitive problems. Clinicians should also get input from the family about whether the patient is stable or worsening.

In addition, neurologists should consider how well the patient is tolerating the current drug, how long he or she has been using it, and how satisfied he or she is with it. The clinician also should consider the patient’s comorbidities and the stage of the patient’s illness. It may be better to treat aggressively in early stages, but aggressive therapy is not necessarily the most effective therapy for a given patient. Finally, if switching therapies is being considered, the neurologist should review the other available drugs, with an eye toward effective and safe drugs that the patient would tolerate and with which the neurologist is comfortable.