July 9, 2007

Question:
With recent reports of progressive multifocal leukoencephalopathy (PML) developing in patients treated with rituximab (thus far confined to patients with systemic lupus erythematosus), would it be prudent to prescreen all patients with brain magnetic resonance imaging (MRI) prior to anticipated treatment?

Answer:
Prescreening patients before use of rituximab with brain MRI is not recommended for the following reasons:

1. Rituximab is indicated for the treatment of rheumatoid arthritis (RA) in patients who have not adequately responded to anti–tumor necrosis factor (TNF) therapy. PML has never been diagnosed in RA patients treated with rituximab. Prescreening RA patients with brain MRI without a specific clinical indication would yield numerous patients with nonspecifically abnormal MRI scans that may not have clinical significance. This would create unnecessary worry and possibly unnecessary and costly workup.
2. Even in the context of significantly immunocompromised patients (eg, those with AIDS, or patients with lymphoma being treated with chemotherapy and radiation therapy) in whom PML may rarely occur, the idea of screening brain MRIs is problematic because of the likelihood of having nonspecifically abnormal scans and uncertainty about how best to triage the finding of an abnormal scan.
3. Although there may be a characteristic set of changes seen on brain MRI in clinically active PML, the appearance of brain MRI images before development of an established clinical picture of PML is not well understood and may be nonspecific.
4. Up to 86% of healthy adults show seropositivity for antibodies to polyomavirus JC (JC virus), the causative agent of PML, and the JC virus has been found in the urine and tonsils of approximately 30% and 39% of healthy adults, respectively. There is no specific biomarker that could inform the clinical meaning of an abnormal brain MRI in a patient without suggestive neurologic symptoms.
5. An excellent review of this clinical problem is Koralnik IJ. Progressive multifocal leukoencephalopathy revisited: has the disease outgrown its name? Ann Neurol. 2006;60:162-173.

Philip Mease, MD