Changes in John Cunningham virus index in Multiple Sclerosis patients treated with different disease-modifying therapies.

BACKGROUND Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated to natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease modifying therapies (DMTs) on JCV index have not been fully explored. OBJECTIVE to evaluate changes in JCV index during treatment with several DMTs. METHODS This longitudinal study evaluated JCV index before starting DMT (T0) and on DMT (T1). RESULTS A total of 260 (65.4% females, mean age 43±11.3 ) were enrolled: 68 (26.2%) treated with fingolimod (FTY), 65 (25%), rituximab or ocrelizumab (RTX/OCR), 37 (14.2%), dimethyl-fumarate (DMF), 29 (11.2%), cladribine (CLD), 23 (8.8%), teriflunomide (TFM), 20 (7.7%), interferon or glatiramer acetate (IFN/GA), and 18 (6.9%) alemtuzumab (ALM). At T1, the percentage of patients with JCV index 1.51 was significantly reduced in RTX/OCR group (51.6% versus 37.5%, p=0.04). In the FTY group, a significant reduction in percentage of patients with JCV index <0.90 was also found (23.5% versus 1.4%, p=0.0006). The mean JCV index was reduced in RTX/OCR and ALM groups, while a significant increase was observed in the FTY group. CONCLUSION DMTs with a T and/or B depleting mechanism of action induced a significant reduction of the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control, while reducing PML risk.