AAN: Another Polyomavirus Appears Reactivated with Natalizumab
SEATTLE, April 28 -- The JC polyomavirus responsible for progressive multifocal leukoencephalopathy (PML) may not be the only such virus reactivated by natalizumab (Tysabri).
In a study of 57 patients receiving natalizumab for relapsing-remitting multiple sclerosis, twelve (22%) saw reactivation of the BK polyomavirus, which can cause nephropathy and hemorrhagic cystitis, reported Roisin Lonergan, M.S., a neurology fellow at St. Vincent's Hospital in Dublin, Ireland.
No cases of clinical disease or other overt adverse effects were seen in the study, which began in January 2007, Dr. Lonergan said in a poster presentation here at the American Academy of Neurology's annual meeting.
Nevertheless, monitoring patients taking natalizumab for BK polyomavirus reactivation and for renal dysfunction may be warranted, she suggested.
The occurrence of three cases of PML, which is often fatal, forced natalizumab off the market in 2005, just a few months after its initial approval. Marketing resumed in June 2006 under a restricted-access program intended to prevent additional PML cases.
Natalizumab is a monoclonal antibody against the alpha4-integrin adhesion molecule. It is believed that this mechanism somehow allows latent infections with the JC polyomavirus, which are extremely common, to become active again.
But the JC virus responsible for PML is not the only common polyomavirus capable of causing significant illness, prompting the Irish study of possible BK virus reactivation.
Such reactivation has been seen in patients receiving kidney transplants and follow-up immunosuppressant treatment. Nephropathy caused by the virus is a frequent cause of graft failure in these patients.
Dr. Lonergan and colleagues prospectively evaluated 57 patients starting treatment with natalizumab.
They found BK virus in urine in three of 36 baseline samples prior to starting on the drug.
Subsequently, the virus was found in urine or blood samples in 12 patients, following a mean of 11.2 natalizumab doses (range 1 to 23).
The researchers also identified JC virus reactivation on one patient after a single dose. PML did not develop.
Nor did any cases of renal dysfunction occur, the researchers found. Renal profiles remained within normal limits in all patients.
Dr. Lonergan said the latter finding should be reassuring to patients on natalizumab therapy.
Absolute CD4- and CD8-positive cell counts did not decrease significantly overall with natalizumab.
However, four of the patients with BK virus reactivation showed transient reductions in CD4-positive cell counts shortly before the virus was detected in urine.
In three of these patients, moreover, a return of CD4-positive cell counts to baseline values paralleled suppression of BK virus replication.
Lily Jung, M.D., a neurologist at Swedish Neuroscience Institute in Seattle, who was not involved with the study, said the findings could be significant.
She noted that urinary tract infections are not uncommon in multiple sclerosis patients. But the possibility that blood in the urine might reflect hemorrhagic cystitis related to BK reactivation, rather than an ordinary urinary tract infection, is a concern.
"They get blood in their urine, and it's very easy to . . . say it's a UTI rather than a reactivation of the polyomavirus," Dr. Jung said.
But she noted that no actual cases have been seen yet, a point echoed by Giancarlo Comi, M.D., a neurologist at Hospital San Raffaele in Milan, Italy, who also was not involved with the study.
He said BK virus reactivation was "theoretically" a concern, but the lack of dysfunction seen in the Irish study suggested that clinicians need not worry about it for now.
"To link this to a new risk, to me, there is no reason [now]," Dr. Comi said.
On the other hand, he suggested the findings could be helpful to virologists in shedding light on the dynamics of polyomaviruses. full report in MedPage Today