Immunoadsorption Better Than 2nd Round of Steroids for MS Relapse
Blood-cleansing process more effective for treatment-resistant relapses
A type of blood-cleansing process called immunoadsorption worked better than a second round of methylprednisolone for treating relapse in multiple sclerosis (MS) patients who failed to respond to a first, standard cycle of the corticosteroid, a study found.
Among people with relapsing MS, immunoadsorption also was associated with greater gains in quality of life, and fewer signs of nerve damage, as compared with a double dose of methylprednisolone.
Moreover, data suggested that this treatment may act by modulating the function of B-cells, a type of immune cell implicated in MS. These findings point to immunoadsorption — IA for short — as a promising approach for treating methylprednisolone-resistant MS relapses.
“Immunoadsorption demonstrated favourable outcomes compared to double-dose methylprednisolone,” the researchers wrote, noting that “outcome differences were significant at discharge and follow-up.”
The study, “Immunoadsorption versus double-dose methylprednisolone in refractory multiple sclerosis relapses,” was published in the Journal of Neuroinflammation.
In MS, the immune system produces antibodies that wrongly recognize myelin, the protective sheath around nerve fibers, as foreign, mounting immune attacks against it. Relapsing forms of MS are characterized by relapses, or periods of symptom worsening, due to abnormal inflammation and immune attacks that cause myelin damage.
The recommended treatment for MS relapses is a high-dose course of methylprednisolone, a type of steroid that works by suppressing inflammation. The therapy is administered directly into the bloodstream (intravenously) at a daily dose of up to 1,000 mg, for three to five consecutive days.
While this approach is effective for many patients, in about one quarter of those with MS, it fails to ease relapse symptoms. A second, double-dose cycle is recommended in such cases.
Investigating immunoadsorption for MS relapse
One alternative to a second round of methylprednisolone is immunoadsorption — though it is more invasive and more expensive.
This process involves collecting a patient’s blood, separating out its liquid component, plasma, and filtering it to selectively remove antibodies, but not other plasma proteins. The filtered plasma is then re-infused into the bloodstream.
By reducing circulating antibodies, this strategy is expected to ease immune attacks on myelin and lessen relapse symptoms.
Previous studies have supported its superiority over plasma exchange — a similar approach that replaces all of a patient’s plasma — in treating steroid-resistant MS relapses.
However, no study to date has compared immunoadsorption’s efficacy against a second, double-dose cycle of methylprednisolone for resistant relapses. In addition, the mechanisms by which immunoadsorption alleviates relapse are not well-understood.
The observational INCIDENT-MS trial (NCT04450030) was designed to directly compare the safety and efficacy of immunoadsorption versus methylprednisolone for treatment-resistant relapses. It also aimed to assess the potential mechanism of immunoadsorption.
From August 2018 to June 2020, 42 patients with relapsing MS who failed to show a good response to a first cycle of methylprednisolone for a relapse were recruited at the University Hospital Muenster, in Germany.
The participants’ median age was 35, and most were in the early stages of the disease. More than half (57%) had not had a prior relapse, and 71% had not received previous treatment.
The most common form of relapse was optic neuritis (52%), characterized by inflammatory damage to the optic nerves that send visual signals from the eyeballs to the brain.
A total of 26 patients (72%) were given a second, double-dose methylprednisolone course of 2,000 mg per day for five days. This was dubbed the MPS group. The other 16 (38%) underwent six sessions of immunoadsorption over 6–8 days. These patients were called the IA group.
These second rounds of therapy were called “escalation treatment.”
Due to incomplete clinical recovery, nine of the 26 patients (35%) who received a second course of methylprednisolone subsequently underwent immunoadsorption, becoming known as the MPS+IA group.
All patients fully completed their escalation treatment regimen, and outcomes were evaluated at discharge from escalation treatment and three months later, as a follow-up.
The study’s primary goal was to evaluate treatment response at discharge, as assessed with changes in the expanded disability status scale, a measure of functional disability. Patients were grouped as full/best recovery or average recovery — together comprising “treatment responders” — or worse/no recovery, known as “treatment non-responders.”
At discharge, the proportion of non-responders in the immunoadsorption group was significantly lower, by more than three times, than among patients receiving methylprednisolone.
Notably, at follow-up, all patients who underwent immunoadsorption, including those in the MPS-IA group, were considered treatment responders. That was in contrast to the nearly half of those in the MPS group who classified as non-responders.
Odds of recovering from the relapse at follow-up versus retaining some disability were 103 times higher in the IA group compared with the MPS groups, and 50 times higher in the MPS-IA group.
Better results with immunoadsorption
Patients undergoing immunoadsorption showed generally better function, quality of life, and nerve function than those in the MPS group, as assessed with validated measures. The blood-cleansing approach also was associated with lower blood levels of nerve damage biomarkers.
Many of these improvements were smaller in the MPS-IA group than the IA group.
All patients in the MPS group and 87.5% of those in the IA group experienced at least one adverse event.
The most common side effects with MPS included high blood sugar, sleep problems, fast heart rate, low potassium, and high blood pressure. A total of 16 MPS-treated patients required temporary insulin treatment and potassium supplements, while four developed clinically significant anxiety, three developed acute psychosis, and one showed liver injury.
With immunoadsorption, common side effects were low blood calcium and low blood pressure. In two cases, the catheter used to draw the blood became dislocated, and one person required antibiotics for an infection associated with the catheter.
To learn more about the underlying mechanisms of immunoadsorption, the researchers examined blood samples collected from patients at discharge and follow-up.
They found that this approach led to significant reductions in B-cells, the type of immune cell that produces antibodies, and greater drops were associated with clinical improvements.
Immunoadsorption also was associated with decreases in a number of other factors found in blood, including antibodies, blood clotting factors, and inflammatory molecules.
Overall, “IA proved to be a promising strategy for steroid-refractory [relapsing MS] and thus should be considered early in treatment algorithms,” the researchers wrote.
“Since the safety profile appeared advantageous to plasma exchange in previous reports and effectiveness appeared superior in outcomes such as [functional status], its use in routine clinical practice should be considered, especially in specialized centers,” the team added.
“Furthermore, our findings indicate that modulation of B cells potentially represents a major mechanism of action of IA treatment,” the researchers concluded.