Measuring the effectiveness of treatments for multiple sclerosis (MS) is complicated; the disease biology is not entirely understood, and symptoms vary from person to person. While doctors and researchers continue to explore new endpoints for clinical trials that evaluate MS therapies, measuring relapse rates remains one of the most common.
Neurologist Enrique Alvarez, M.D., Ph.D., at the University of Colorado, Denver, discusses the importance of continuing to evaluate potential new therapies based on their ability to reduce relapse rates, along with newer measures that are bolstering these evaluations.
How do researchers measure the efficacy of new treatments for MS?
“Relapse rates are a benchmark for measuring the efficacy of new MS treatments in clinical trials. A relapse occurs when a new neurological symptom emerges or an old symptom gets worse for at least 24 hours. MS can cause a variety of symptoms such as vision loss, pain, fatigue or impaired coordination.”
“Signs of a relapse can be reported by the patient, and may have an immediate impact on the quality of a patient’s life. Relapse rates also tend to go hand-in-hand with disability rates; relapses are often associated with some lasting disability.”
How else are researchers measuring efficacy in MS?
“We have set criteria about how to determine a relapse, but these assessments are often subjective and can be ‘noisy.’ This noise can be associated with a pseudo-relapse, which is the return of an old symptom because of factors unrelated to MS, such as stress, fever or an infection. MS symptoms can also fluctuate throughout the day, affecting a patient’s assessment.”
“The challenge is finding a way to measure clinical events across all the patients in a study. For example, how do you compare a patient who might have bladder function issues with a patient who has vision loss? That type of comparison remains a challenge.”
These newer measurements are valuable, but we still need to look at relapse rates.
How are researchers overcoming the challenges of measuring efficacy in MS trials?
“We have been including more objective, less noisy measures such as MRI [magnetic resonance imaging] metrics in trials. MRI measurements can serve as a substitute for clinical outcomes reported by patients.”
“In MS, the body’s immune system causes inflammation and damage in the brain, resulting in scar tissue, which we call a lesion. MRI can measure new and growing lesions in the brain. The more lesions a patient has, the more likely he or she will experience worsening symptoms and future relapses.”
SECONDARY MEASUREMENTS SUCH AS MRI BRAINS SCANS CAN HELP MEASURE THE EFFICACY OF NEW MS TREATMENTS.
What are some newer measures that are being explored?
“Newer measures are exploding. We’re starting to see a host of cognitive testing measures. Balance is being evaluated more. There are kinetic measures, like those you can find on a smartphone app, to see how much the patient is walking. We’re trying to get a sense of how the patient feels their life is changing on the tested therapy. You lose a little of the objectivity that you get with a measurement like MRI, but you gain a better sense of how the patient feels they’re doing.”
Could these newer measurements replace relapse rates as a benchmark?
“These newer measurements are valuable, but we still need to look at relapse rates. Rather than replace them, we’ll be more likely to see combinations of multiple endpoints used to determine the efficacy of tested therapies in trials. The more measurements, the better.”
To learn about how relapses can affect the lives of people living with MS, read “World MS Day: MS Doesn’t Stop Me from Living a Life I Love.”