Two multiple sclerosis (MS) patients developed severe brain inflammation after being treated with Lemtrada (alemtuzumab), researchers report, raising questions about the therapy. A definite link between the lesions and the treatment, however, was not established.

The patients’ symptoms were successfully controlled with a blood transfusion and treatment with rituximab (brand name Rituxan, among others), according to the report, “ Severe B-cell-mediated CNS Disease Secondary To Alemtuzumab Therapy .” It was published in the journal The Lancet Neurology.

Lemtrada is an antibody that specifically recognizes the CD52 protein that is present on the surface of certain immune cells, such as the T- and B-lymphocytes, thereby blocking their action. Clinical trials showed Lemtrada was more efficient in reducing relapses and brain loss than treatment with interferon beta-1a, and data from three Phase 3 trials, involving about 1,500 Lemtrada-treated MS patients, showed that most autoimmune side effects were mild or moderate.

The MS patients in the case report (a 41-year-old man and a 25-year-old woman) received Lemtrada to treat relapsing MS and inflammation affecting the nervous system. But six months after the treatment, the symptoms had significantly worsened. Using magnetic resonance imaging (MRI), researchers detected inflammatory ring-shaped areas in their brains that had not been there before treatment.

Both received a blood plasma transfusion and treatment with rituximab, an antibody that targets B-lymphocytes. Rituximab improved the inflammation, leading researchers to believe the cells were involved in the ring-shaped lesions.

The combined treatment improved the patients’ symptoms and helped maintain disease stability a year later. However, the team was not able to tell whether the brain lesions represented increased MS activity or were a side effect associated with Lemtrada.

“These two patients might represent the first recognized cases of severely exacerbated (nervous) inflammation after alemtuzumab therapy in multiple sclerosis,” the researchers wrote. “The exacerbated inflammation seen in our patients is consistent with the time frame in which B-cell repopulation and peripheral expansion occur following alemtuzumab treatment.

“Thus, it remains to be determined if the disease observed in these two patients after treatment is due to worsening of multiple sclerosis or to the development of secondary (nervous system)-directed autoimmunity,” they wrote.

Lemtrada was approved by the FDA in 2014 as a treatment for relapsing MS, but safety concerns led to the recommendation that its use “generally be reserved for patients who have had an inadequate response” to two or more treatments, Genzyme announced at the time.