ACTRIMS 2025: Ocrevus may help treat MS paramagnetic rim lesions
Therapy’s use linked to myelin increases, iron reductions in MS patients
Treatment with Ocrevus (ocrelizumab) may have a beneficial effect on paramagnetic rim lesions — known as PRL, these are a type of chronic inflammatory lesion — in people with multiple sclerosis (MS), according to a newly shared analysis.
PRLs, a form of nerve damage seen in MS, have been associated with disability progression in the neurodegenerative disease. An iron rim, reflecting the presence of iron-containing inflammatory immune cells surrounding the lesion, and loss of myelin, the fatty substance surrounding nerve cells that’s progressively destroyed in MS, are two hallmark features of these lesions.
The new analysis found benefits such as reductions in iron and increases in myelin in MS patients with PRLs who were treated with Ocrevus.
The findings altogether suggest “a potential reduction in pro-inflammatory activity and increased remyelination” after starting Ocrevus treatment, according to Kimberly Markowitz, of Cornell University in New York.
Markowitz presented the results in a talk at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, being held Feb. 27 through March 1, in Florida and virtually. The talk was titled “Quantifying Ocrelizumab’s Impact on Paramagnetic Rim Lesions in Multiple Sclerosis Using Source Separation.” The work was funded by Genentech, which markets Ocrevus.
Researchers develop new tool for studying lesions in MS
MS is caused by inflammation that drives damage to the brain and spinal cord. These areas of damage, called lesions, can be visualized with MRI scans. Lesions can be active, representing areas of ongoing inflammation, or inactive, representing sites of damage from a previous inflammatory attack but where there is no current inflammatory activity.
PRLs, sometimes known as smoldering lesions, are a type of chronic inflammatory lesion seen in MS. They’re characterized by a rim of pro-inflammatory iron-containing immune cells, ongoing demyelination, and permanent damage to nerve cells. In recent years, scientists have come to recognize that these lesions may be important contributors to disability progression in MS.
Ocrevus is a disease-modifying therapy (DMT) used to deplete levels of B-cells, which are immune cells that play a key role in MS inflammatory attacks. The drug is known to be highly effective at reducing acute inflammation, but its impact on chronic inflammation is not well established, according to Markowitz.
Quantitative susceptibility mapping, known as QSM, is an advanced MRI technique used to detect PRLs and to quantify the iron-laden immune cells within them. An earlier study using this technique found that Ocrevus and other B-cell depleting therapies did not fully resolve PRLs.
However, demyelination is also a key feature of PRLs, which isn’t accounted for with standard QSM analyses.
“Our previous research has demonstrated that both a deposition of iron as well as myelin loss, both contribute to an increase in QSM signal within MS lesions,” Markowitz said.
As such, the team now developed an algorithm that can separate the relative contributions of iron and myelin to the QSM output so as to get a better picture of how treatments might be influencing these distinct features of PRLs.
Analysis used data from MS patients treated with Ocrevus in ongoing trial
The goal of the recent study was to apply the algorithm to imaging data collected from MS patients before and after starting on Ocrevus in an ongoing clinical trial.
The analysis involved 29 patients, most of whom (82.8%) had relapsing-remitting MS. Of nearly 1,500 total brain lesions, 6.67% were PRLs, with a median of three such lesions per patient. Patients were followed for a median of about four years both before and after starting Ocrevus.
QSM was split into two components: QSMp, which reflects iron burden, and QSMn, reflecting myelin. All QSM values are expressed in parts per billion, or ppb.
Before the start of Ocrevus, PRLs were found to have significantly higher QSMp and lower QSMn than other types of lesions. QSMp was significantly reduced after Ocrevus was started, while QSMn was increased, generally indicating that the treatment may be reducing inflammatory immune cells and promoting myelin restoration.
Within PRLs, average QSMp values had been declining at a rate of 0.457 ppb per year before Ocrevus, which accelerated to 1.041 ppb per year after starting the treatment. Meanwhile, QSMn values in PRLs had been increasing at an average rate of 0.454 ppb/year pre-treatment, which accelerated to a yearly increase of 0.813 ppb after Ocrevus was started.
[Ocrevus] is associated with a decline in iron source … and an increase in myelin … after treatment initiation.
Analyses indicated these rate changes occurred in the first six months of initiating Ocrevus treatment.
“[Ocrevus] is associated with a decline in iron source, as seen in the decrease in QSMp, and an increase in myelin, as seen as the increase in QSMn after treatment initiation,” Markowitz said.
In addition to demonstrating a possible role for Ocrevus in resolving PRLs, the findings also highlight the value of the researchers’ QSM analysis approach for quantifying these two distinct processes within the lesions.
Markowitz noted that the approach “provides valuable insight for monitoring and optimizing treatment strategies.”
In future studies, the researchers plan to further optimize their analysis approach, and to apply it to data from larger groups of patients. This will allow them to explore how different DMTs might influence MS lesions.
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