#ACTRIMS2018 – Combo Can Stop Tysabri-related PML Infection from Worsening, Case Study Shows

A combination of an anti-viral therapy and the anti-depressive mirtazapine can stop the worsening of an infection linked to the multiple sclerosis therapy Tysabri (natalizumab), a case study suggests.

The infection, John Cunninghan polyomavirus, can cause a potentially fatal brain infection known as  progressive multifocal leukoencephalopathy, or PML. Both infections are caused by viruses.

Early treatment with mirtazapine and either IV-administered Vistide (cidofovir) or its oral formulation, brincidofovir, helped protect the nerve cells of four people with MS and Tysabri-associated PML, the case study showed.

Researchers presented the findings at the Third Annual Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2018 in San Diego, Feb. 1-3. The poster presentation was titled “Treatment of Natalizumab-Induced PML with Cidofovir or CMX001 (brincidofovir) and Mirtazapine.”

Previous studies had shown that the Vistide-mirtazapine combo helped patients with a compromised immune system who developed PML. Vistide is marketed by Gilead Sciences in the U.S., and by Pfizer elsewhere. Mirtazapine is sold under several brand names.

The combo also helped people with autoimmune diseases, such as systemic lupus erythematosus, studies demonstrated. An autoimmune disease is one in which the immune system attacks healthy tissue instead of invaders.

Until the case study, there was no evidence that the combo would help MS patients with therapy-associated PML.

University at Buffalo researchers studied four MS patients with Tysabari-related PML whom doctors treated with mirtazapine plus Vistide or brincidofovir. Chimerix is developing brincidofovir.

The Tysabri-related PML patients included two men and two women. One received mirtazapine and brincidofovir twice a week. The others received mirtazapine and intravenous Vistide every two weeks.

With the combo reining in their virus significantly, all four survived more than five years. The neurological symptoms of three showed major improvements, although they experienced mild to moderate cognitive loss.

Despite the combo’s benefits, one patient remained physically impaired because doctors diagnosed him with PML late, which meant his treatment started late. He died five years later.

During the treatment, two patients developed severe diarrhea. And the patient receiving brincidofovir developed treatment-related bowel inflammation.

A review of the four cases “demonstrates that early initiation of treatment with CDV [Vistide] or CMX001 and concurrent mirtazapine can halt the progression of natalizumab [Tysabri]-related PML and aid in neurologic recovery,” the researchers wrote.

They called for additional studies on the combo’s safety and ability to treat drug-related PML.