Abstract
Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening brain infection caused by the John Cunningham virus. PML is a known adverse effect associated with molecular-targeted drugs and immunosuppressive agents. Recent concerns have emerged regarding the link between methotrexate (MTX) and PML. However, limited information exists on the influence of concomitant drug use in rheumatoid arthritis (RA) treatment, where various medications are often used together. Methods: To explore treatment patterns and patient background that affect PML reporting in RA, we analyzed data on RA cases from the Food and Drug Administration Adverse Event Reporting System (FAERS; JAPIC AERS) database between 1997 and 2019. Results and Discussion: Our analysis revealed significantly elevated crude and adjusted reporting odds ratios (aROR) for MTX, rituximab (RIT), azathioprine, and cyclophosphamide. When considering treatment patterns, the concomitant use of MTX and RIT showed a higher aROR than using MTX or RIT alone. Additional TNF-α inhibitors or glucocorticoids did not increase PML reports. Moreover, male sex and older age were associated with increased PML reports. While limitations are inherent in studies using spontaneous reporting data, our exploratory assessment suggests an association between PML and the combination of MTX and RIT and a higher risk in men and older patients. These findings help enhance our understanding of PML risk factors in the context of RA treatment.