Contributions
Abstract: P1259
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: the prediction of the risk of progressive multifocal leukoencephalopathy (PML) is crucial to guide natalizumab (NTZ) prescription and ensure a higher safety use. The JCV index (a corollary to antibody titer) is a predictive factor of PML.
Case presentation: here we report a case of a 55-year-old female diagnosed with multiple sclerosis in 1996. Because of a continued clinical disease activity despite interferon, she was switched to NTZ. A total of 84 infusions were administered between 2011 and 2016. She never received any prior immunosuppressor and has been tested negative for anti-JCV antibodies: index at 0.22 in 06/2014 and 0.11 in 06/2015 and 10/2015. The annual MRI were strictly stable. During a routine follow-up, the patient complained of a right-sided lower limb paresis. NTZ was immediately stopped. Brain magnetic resonance imaging revealed a sub-cortical white matter lesion, hypoT1, hyperT2 in the left parietal lobe invading the U-fibers in DIR sequence. PML was suspected then confirmed by detection of JCV-DNA in the CSF (2 analyses: 11 then 68 copies/ml). The peripheral CD4+ T-cell count was 1149/mm3, CD8+ at 395/mm3. Note that the JCV index was still negative at the diagnosis and 15 days later. We investigate the lymphopenia and found a probable common variable immune deficiency (CVID) with severe hypogammaglobulinemia (3g/dL), surprisingly asymptomatic until now. A JCV seroconversion was noted at 3 months (index at 3.48).
Discussion: it is well-known that PML risk is influenced by NTZ duration, prior use of immunosuppressors and seropositivity for the JCV. The JCV seronegativity status does not allow to exclude any risk of PML. Indeed, de novo infection with seroconversion is theoretically possible and underestimate rate of infection appears likely (in case of low viremia). One recent publication reports a NTZ-related PML diagnosed 2 weeks after negative anti-JCV antibody assay and 2 others PML due to NTZ were tested negative (prior to diagnostic) among the 541 reported cases. In our case, we can hypothesize that the JCV index were false negative results as the asymptomatic CVID imply a fail in humoral responses.
Conclusion: this case must not undermine the central role of the JCV index in predicting the risk of PML. However, it seems wise to regularly control the blood lymphocyte phenotype and immunoglobulins. CVID is the one of the most common causes of adult immunodeficiency.
Disclosure: N. Hadhoum: travel fees from Biogen, Teva
V Neuville: nothing to disclose
P. Vermersch: Honoraria and consulting fees from Biogen, Genzyme-Sanofi, Bayer, Novartis, Teva, Merck-Serono, GSK and Almirall, Research supports from Biogen, Bayer, Novartis and Merck-Serono
Abstract: P1259
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: the prediction of the risk of progressive multifocal leukoencephalopathy (PML) is crucial to guide natalizumab (NTZ) prescription and ensure a higher safety use. The JCV index (a corollary to antibody titer) is a predictive factor of PML.
Case presentation: here we report a case of a 55-year-old female diagnosed with multiple sclerosis in 1996. Because of a continued clinical disease activity despite interferon, she was switched to NTZ. A total of 84 infusions were administered between 2011 and 2016. She never received any prior immunosuppressor and has been tested negative for anti-JCV antibodies: index at 0.22 in 06/2014 and 0.11 in 06/2015 and 10/2015. The annual MRI were strictly stable. During a routine follow-up, the patient complained of a right-sided lower limb paresis. NTZ was immediately stopped. Brain magnetic resonance imaging revealed a sub-cortical white matter lesion, hypoT1, hyperT2 in the left parietal lobe invading the U-fibers in DIR sequence. PML was suspected then confirmed by detection of JCV-DNA in the CSF (2 analyses: 11 then 68 copies/ml). The peripheral CD4+ T-cell count was 1149/mm3, CD8+ at 395/mm3. Note that the JCV index was still negative at the diagnosis and 15 days later. We investigate the lymphopenia and found a probable common variable immune deficiency (CVID) with severe hypogammaglobulinemia (3g/dL), surprisingly asymptomatic until now. A JCV seroconversion was noted at 3 months (index at 3.48).
Discussion: it is well-known that PML risk is influenced by NTZ duration, prior use of immunosuppressors and seropositivity for the JCV. The JCV seronegativity status does not allow to exclude any risk of PML. Indeed, de novo infection with seroconversion is theoretically possible and underestimate rate of infection appears likely (in case of low viremia). One recent publication reports a NTZ-related PML diagnosed 2 weeks after negative anti-JCV antibody assay and 2 others PML due to NTZ were tested negative (prior to diagnostic) among the 541 reported cases. In our case, we can hypothesize that the JCV index were false negative results as the asymptomatic CVID imply a fail in humoral responses.
Conclusion: this case must not undermine the central role of the JCV index in predicting the risk of PML. However, it seems wise to regularly control the blood lymphocyte phenotype and immunoglobulins. CVID is the one of the most common causes of adult immunodeficiency.
Disclosure: N. Hadhoum: travel fees from Biogen, Teva
V Neuville: nothing to disclose
P. Vermersch: Honoraria and consulting fees from Biogen, Genzyme-Sanofi, Bayer, Novartis, Teva, Merck-Serono, GSK and Almirall, Research supports from Biogen, Bayer, Novartis and Merck-Serono