KYOTO, Japan — The antimalarial drug mefloquine may prove to be an effective treatment for progressive multifocal leukoencephalopathy (PML) in patients not infected with HIV, a small, preliminary study suggests.

Although the results of a study did not reach statistical significance, probably because of the small number of patients studied, the absolute numbers suggest a beneficial effect of the drug against JC virus, the cause of PML, the researchers, led by Yoshiharu Miura, MD, from Komagome Hospital, Tokyo, Japan, conclude.

The results were presented here at the XXIII World Congress of Neurology (WCN).

PML is a usually fatal disease affecting the subcortical white matter of the central nervous system. Previous in vitro studies have shown anti–JC virus activity with mefloquine, the authors note in their abstract. “While case reports have shown that mefloquine improves the outcomes of patients with PML,” they write, no large-scale studies have yet shown that.

One trial, an open-label, randomized, proof-of-concept study published in 2013 in the Journal of Neurovirology, did not find any evidence of anti–JC virus activity with mefloquine and was halted early for futility. “Our study is too small to definitively rule out mefloquine activity against PML, but given the inability to find any evidence of activity in this study, we would not advocate empiric use of this therapy for PML patients,” those researchers concluded.

In the current analysis, a retrospective study of 56 patients diagnosed with probable or definite PML, Dr Miura and colleagues aimed to determine the clinical effects of mefloquine on PML.

Patient data were derived from the PML information center at Komagome Hospital and the Japan National Institute of Infectious Diseases. Forty patients had been treated with 275 mg/day for 3 days and then 275 mg/week for a total of 24 weeks. The remaining 16 patients did not receive mefloquine.

Nineteen patients were infected with HIV, and 37 were not. For HIV-infected patients, mefloquine did not appear to be particularly helpful, Dr Miura reported.

Among the 37 patients without HIV, 29 received mefloquine (average age, 58.9 years) and 8 did not (average age, 82 years).

For the patients receiving mefloquine, the predominant diagnoses were collagen diseases (n = 11 [7 with systemic lupus erythematosus]) and lymphoma (n = 5).

Among the patients receiving mefloquine, the drug “improved clinically about 30% of patients,” Dr Miura said. “In non-HIV PML, mefloquine may increase life expectancy.”

Among the 29 patients receiving the drug, 8 showed clinical improvement and 4 had nonprogression of the PML (41% improvement/nonprogression). There was no effect among the remaining 15 patients, 11 of whom had early mortality, and an additional 2 patients discontinued the drug.

Among the patients who did not receive mefloquine, none showed clinical improvement and 2 had clinical nonprogression (25% nonprogression). The 2 patients who did not receive mefloquine and did not progress received mirtazapine, an antidepressant that may work in PML by blocking JC virus from entering glial cells by blocking the 5HT2a receptor, the authors noted. There was no effect among 6 patients, who had subacute progression and early death.

Table. Outcome of PML Patients Not Infected With HIV, by Treatment

Endpoint Treated with Mefloquine (n = 29) No Mefloquine (n = 8)
Clinical improvement (n) 8 0
Clinical nonprogression (n) 4 2


Critically ill patients were not given mefloquine because the drug was seen as not applicable to them.

Diederik van de Beek, MD, from the Academic Medical Center, Amsterdam, the Netherlands, commented to Medscape Medical News that “there’s always confounding by indication so you might try out this drug in a patient you think has a favorable outcome anyway.”

In fact, the oldest patients in the group without HIV infection (average age, 82 years) did not receive mefloquine.

“Or, the other way around — you might give this drug when you think this patient has nothing to lose anymore. So the way to go is…to do a randomized, controlled trial, and the first randomized, controlled trial was a neutral trial,” he said.

The authors intend to pursue the question and showed the design of a randomized, controlled trial of mefloquine for PML now in the planning stages.

The study had no commercial funding. Dr Miura and Dr van de Beek have disclosed no relevant financial relationships.

XXIII World Congress of Neurology (WCN). Abstract 420. Presented September 18, 2017.

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Daniel M. Keller, PhD