Rituximab Use Associated With PML in Arthritis

This may be an underestimate because it's likely that more patients have not been accurately diagnosed or reported to the company, they added.

This “modest” incidence is lower than that reported for natalizumab-associated PML (1 in 1,000 patients exposed for more than 2 years) or for efalizumab-associated PML (1 in 400 exposed patients).

The need for effective treatments of rituximab-associated PML is “urgent.” Antiviral therapy has not been shown to be effective. Some clinicians still try using cytosine arabinoside and cidofovir, “in spite of significant evidence that they are not effective.”

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,” they 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.