Novel Interventions with Favorable Resolution of Natalizumab-Induced Progressive Multifocal Leukoencephalopathy (PML) (P07.062)

Abstract

Objective: To describe the outcomes of early detected progressive multifocal leukoencephalopathy (PML) in natalizumab-treated multiple sclerosis (NTMS) patients utilizing novel interventions. PML is an opportunistic brain infection caused by the JC virus (JCV) in NTMS patients. Background To address the need for effective approach to ameliorating PML. Design/Methods: Our empirical protocol for early diagnosis of PML in NTMS patients uses cranial MRIs at 4-6 month intervals or with new symptoms. Diagnosis was based on PML suspected MRI findings and positive JCV PCR in the CSF. Management consisted of plasma exchange, subcutaneous filgrastim 5 mg/kg/day (to restore lymphocyte adhesion capacity and immuno surveillance), oral maraviroc 150 mg twice daily (to modulate T cell recruitment), and oral mefloquin 300 mg/day and mirtazapine 50 mg/day (for their putative anti JCV effects). Patients were concurrently monitored using weekly contrast-MRIs and received intravenous corticosteroids upon emergence of immune reconstitution inflammatory syndrome (IRIS). Results: Six patients with NTMS were diagnosed with PML after 29-54 months of treatment. MRI discovered PML in two asymptomatic and two mildly symptomatic ones. Medications were well tolerated. Except for transient worsenings and seizures during IRIS, these patients did not significantly progress, remaining independent. Two of them already resumed employment, and the third one is soon expected to, as well. The two patients who were more severely symptomatic at diagnosis suffered intensified deficits, precluding independence. MS activity reoccurred in two patients after 6 and 8 months. Duration of post PML follow up 6-28 months. Conclusions: Our novel approach to PML in NTMS patients included monitoring that allowed very early diagnosis and administration of filgrastim and maraviroc, which likely contributed to the favorable clinical outcome in four patients. The two symptomatic at diagnosis patients remain incapacitated, though this regimen may have prevented fatal outcomes. The present interventions are of clinical significance and warrant further exploration. Disclosure: Dr. Stefoski has received personal compensation for activities with Biogen Idec, Acorda, Serono, Elan, and Teva Neuroscience. Dr. Stefoski has received royalty payments from Acorda Therapeutics. Dr. Stefoski has received research support from Biogen Idec, Novartis, Serono, and Pfizer. Dr. Ko has received personal compensation for activities with Biogen Idec, Serono, Inc., and Teva Neuroscience for consulting services. Dr. Javed has received personal compensation for activities with Teva Neuroscience, Bayer Pharmaceuticals, Serono, Inc., Novartis, Questcor and Biogen Idec as a consultant and/or speaker. Dr. Balabanov has received personal compensation for activities with Biogen Idec, Teva Neuroscience and Genzyme as a consultant, and speaker bureau honoraria from Biogen Idec and Teva Neuroscience.Dr. Balabanov has received research support from Biogen Idec.