Incidence and risk factors for Progressive Multifocal Leukoencephalopathy among patients with selected rheumatic diseases

Abstract

We conducted a large, population-based study to describe the incidence and risk factors for progressive multifocal leukoencephalopathy (PML) among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS) using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services (CMS) from 2000–2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data >= 6 months prior to PML diagnosis. Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6/100,000 patients). Most PML cases had HIV and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months(all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2/100,000 patients with autoimmune diseases who did not have HIV or malignancy. PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.

The human JC polyomavirus (JCPyV): virological background and clinical implications

“…PML is a demyelinating disease preferentially affecting the white brain matter and is caused by the cytopathic replication of JCPyV in myelin sheath-producing oligodendrocytes. A Swedish and a US study estimated the incidence of PML in the general population as 0.3 per 100 000 person years (95% CI 0.1-0.6) compared to 1.0 (95% CI 0.3-2.5) for patients with rheumatoid arthritis (165)(166)(167). Similar data were reported for a US study estimating PML in systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disease as 4, 0.4, and 2 per 100 000 hospital discharges, respectively, whereas the PML incidence was 0.2 per 100 000 hospital discharges in the background population (167).…”

Treatment considerations in patients with concomitant viral infection and autoimmune rheumatic diseases

“…Another study in the USA used data from Medicare and Medicaid Services, and a PML incidence of 0.2 per 100,000 patients was found among 2,030,578 patients with ARDs. Of nine patients, who used bDMARDs prior to PML hospitalization, three (one receiving infliximab for inflammatory bowel disease, and the other two rituximab for RA) received them within 3 months [152]. One study found the estimated risk of PML in patients with RA receiving rituximab to be 1:25,000 users; unfortunately, this calculation was based on case reports and number of exposures, and not from a case-controlled study [153].…”

Use of Rituximab in the Management of Sjögren’s Syndrome

“…Biologic therapies, including RTX, are also potentially associated with an increased risk of progressive multifocal leukoencephalopathy [51]. This is a rare, fatal, central nervous system demyelinating disease that results from reactivation of the JC virus, which usually occurs in immunosuppressed hosts.…”