New study connects immune cell behavior to Mavenclad response in MS
Findings point to regulatory T-cells as a factor in treatment outcomes
Written by |
• Mavenclad response in multiple sclerosis is linked to immune cell behavior.
• Greater resistance of certain regulatory T-cells to Mavenclad was associated with poorer treatment response.
• Changes in regulatory T-cells and serum neurofilament light chain (NfL) levels may help reflect treatment response.
A new study suggests that how certain immune cells respond to Mavenclad (cladribine) may help explain why the treatment works well for some people with multiple sclerosis (MS), but less so for others.
The researchers found that regulatory T-cells, or Tregs — immune cells that normally help keep inflammation in check — are relatively resistant to reduction with Mavenclad. This resistance, particularly among resting Tregs, was linked to a poorer treatment response.
Although the study involved a small number of patients, the findings suggest that changes in Treg levels following Mavenclad treatment may reflect how well the therapy is limiting nerve-cell damage, as estimated by blood levels of a biomarker called neurofilament light chain (NfL).
Study examines how immune cells respond to Mavenclad
“In this study, we show that, in patients with MS undergoing [Mavenclad] therapy, Tregs (and especially the resting Tregs) are less susceptible to reduction, but such resistance is associated with a poorer response to therapy,” the researchers wrote.
The study, “Treg Susceptibility to Cladribine-Induced Depletion Correlates With Therapy Response in Patients With Multiple Sclerosis,” was published in Neurology: Neuroimmunology and Neuroinflammation.
MS is characterized by inflammation that damages healthy tissue in the brain and spinal cord. Many immune cells play a role in this inflammation, including T-cells.
T-cells come in many subtypes with different roles. Most, called conventional T-cells, promote inflammation, while a smaller group (Tregs) help prevent unnecessary immune attacks.
Growing evidence suggests that Tregs may not function properly in inflammatory diseases such as MS, which could allow harmful inflammation to persist.
Mavenclad is a short-course oral therapy approved in the U.S. for relapsing forms of MS. It works to kill conventional T-cells and other inflammatory immune cells that drive MS, but its impact on Tregs has not been well studied.
Researchers analyzed immune cells before and after treatment
Using blood samples collected from 11 people with MS before and after starting Mavenclad, researchers in Italy examined how the treatment affected Tregs.
The results showed that conventional T-cells were strongly reduced by Mavenclad, while overall Treg levels did not change significantly. Closer analyses revealed that activated Tregs declined after treatment, but resting Tregs appeared largely resistant.
Resting Tregs produced higher levels of certain proteins that help cells avoid apoptosis, or programmed cell death. This may help explain why these cells were less affected by treatment than other immune cell types.
Like many other MS therapies, Mavenclad can reduce levels of neurofilament light chain (NfL), a well-established marker of nerve damage. In this study, differences between responders and nonresponders were most evident in resting Tregs, which declined in responders but appeared more resistant in nonresponders.
Results point to a possible role for regulatory T-cells
Based on these findings, the researchers suggested that Mavenclad’s effects on Tregs may play a role in how well the therapy controls inflammation. They proposed that reducing dysfunctional Tregs could allow new immune cells to repopulate and better regulate inflammatory activity.
“In this study, we uncovered a novel mechanism involved in [Mavenclad]-based therapy for MS. According to our data, the circulating compartment of [resting] Tregs is restrained along therapy and this associates with clinical response,” the scientists concluded.
The researchers emphasized that this analysis was limited to a small number of patients and was based on statistical correlations only. As a result, the findings cannot establish cause-and-effect, and larger studies will be needed to confirm and expand on the results.
Mavenclad is sold in the U.S. by EMD Serono (known as Merck KGaAm, Darmstadt, Germany, outside the U.S. and Canada), which was not involved in this study.
