Mefloquine hydrochloride has shown in vitro activity against JC virus and was used "in several of our cases," but failed to show efficacy in a recent clinical trial. "Similarly, clinicians continue to prescribe mirtazapine on a theoretical basis, related to its potential efficacy in blocking serotonin receptors used for viral entry, despite absence of documented clinical efficacy," the investigators said.
Plasma exchange has become standard practice for natalizumab-associated PML, but it is only likely to speed immune recovery in RA patients taking rituximab if PML is discovered shortly after an infusion of the drug.
If patients develop immune reconstitution inflammatory syndrome, that "provides an additional potential therapeutic avenue." High-dose corticosteroid pulses – "often 1 g of IV methylprednisolone daily for 5 days, which is repeated if symptoms respond and then recur" – may halt neurologic decline and initiate recovery. "Physicians should be aware that this may be required even when the CD20 count suggests ongoing immune compromise" from the rituximab therapy, they added.
"The present cases support the possibility that with early diagnosis and careful management [of immune reconstitution inflammatory syndrome], patients may survive this complication, some with modest deficits," Dr. Clifford and his colleagues said.
"It is reasonable to encourage support and therapy for these patients, since the dire prognosis of PML acquired when associated with advanced malignancy or AIDS may be exaggerated when considering this disease in other settings. Indeed, current experience with natalizumab suggests survival of as many as 70%-80% of patients with PML with concentrated efforts for early detection and reversal of immunosuppression," they noted.
This study was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Allergy and Infectious Diseases. Dr. Clifford and his associates reported ties to Bavarian Nordic, Biogen Idec, Bristol-Myers Squibb, Genentech (maker of rituximab), Genzyme, GlaxoSmithKline, Lilly, Millennium, NeurogesX, Novartis, Pfizer, Schering-Plough, Tibotec, and Wyeth.