Research News: Chronic Active Lesions Signify Aggressive Forms of MS

In August of this year, the National Institutes of Health (NIH) published a news release explaining the connection between chronic active lesions and more aggressive as well as disabling forms of multiple sclerosis (MS). Using a high-powered 7-tesla magnetic resonance scanner (MRI), researchers were able to identify these types of “smoldering” lesions, which are areas of damaged myelin (the protective covering to the nerves). This damage is caused by an attack on the central nervous system (CNS) by one’s own immune system.

While many MS lesions will either fully or partially heal, these chronic active lesions appear to “actively expand or smolder” for many years. However, identifying these more active types of lesions and understanding their role in MS has been a challenge to researchers in the past. Using the high-powered MRI, investigators have since confirmed that these chronic active lesions have a dark rim encompassing the lesion, and this has allowed researchers to observe how each lesion evolves in connection with the disease activity each patient experiences.

Conducting brain scans on 192 individuals with MS who were participating in a trial at the NIH’s Clinical Center, the investigators discovered that the greater the number of rimmed lesions, the more aggressive or disabling a person’s MS would be. The results showed that unrelated to whatever treatment one was receiving, 44% of participants only had lesions without a rim; 37% had one to three lesions with rims; and 22% had four or more rimmed lesions. Those in this latter group – with four or more chronic active lesions – were 1.6-times more likely to be diagnosed with progressive MS versus those individuals who did not have any lesions with rims. Additionally, these patients were found to have less white brain matter and smaller basal ganglia – a part of the brain that processes information for coordination and movement.

The discovery of these “smoldering” rimmed lesions and the technology needed to identify them will help to predict which patients will experience the most aggressive forms of MS. This discovery may also assist with the development of better treatments.

Investigational Oral Medication Reduces Number of Lesions on MRI

Evobrutinib (M2951) is an oral medication being evaluated for potential use in relapsing forms of multiple sclerosis and in secondary-progressive MS. The agent inhibits Bruton’s tyrosine kinase (BTK), an enzyme that regulates the function of B cells and macrophages, components of the immune system shown to play a role in MS.

A recent Phase II study of 267 adults with relapsing forms of MS examined how various doses of evobrutinib affected the total number of T1 gadolinium-enhancing lesions seen on magnetic resonance imaging (MRI) at weeks 12, 16, 20, and 24 of treatment versus placebo. The study also assessed safety, the annualized relapse rate (ARR), and MRI findings at weeks 24 and 48.

The total number of T1 gadolinium-enhancing lesions was significantly reduced in patients receiving 75 mg of evobrutinib daily or twice daily. The ARR over 48 weeks was 0.25 for patients receiving 75 mg of evobrutinib once daily and 0.11 for those receiving 75 mg of the agent twice daily, as compared to 0.37 for the placebo group over 24 weeks. Significant elevations in liver enzymes affected up to 5.4% of patients receiving evobrutinib. The study’s authors concluded that their findings supported further study of the agent.

Progress Toward Identifying a Tysabri Dosing Schedule that Best Balances Benefits and Risk

Tysabri® (natalizumab) reduces disability and relapses in relapsing-remitting multiple sclerosis (RRMS), but also increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that can be life-threatening. Three factors appear to drive the increased risk of PML associated with taking Tysabri: longer use of the disease-modifying therapy (DMT), particularly use beyond two years; prior treatment with an immunosuppressant agent; and having anti John Cunningham Virus (anti-JCV) antibodies.

With these risk factors in mind, clinicians regularly consider a person’s past treatment history and test them for anti-JCV antibodies when assessing whether he or she is a candidate for Tysabri. Additionally, to help more people obtain the benefits of the DMT while minimizing their risk for PML, researchers have been studying whether spreading out the dosing schedule for Tysabri can reduce the risk associated with the medication while maintaining its effectiveness.

The approved dosing schedule entails an intravenous infusion of 300 mg every four weeks. Data collected from the TOUCH prescribing program sponsored by Biogen, which markets Tysabri, indicates that extending the interval between infusions to up to three months can significantly reduce the risk of PML, with a risk reduction of up to 90% seen in one analysis. Researchers will need to continue to collect and analyze data from the TOUCH prescribing program to confirm these findings.

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to

Portions written by Susan Wells Courtney, MSAA Senior Writer, and Tom Garry, Medical Writer

Reviewed by Barry A. Hendin, MD, MSAA Chief Medical Officer