Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment

Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at T12, whereas it remained similar for the HC group (35–40%). Viremia first occurred 6 months after treatment in MS patients and increased after 12 months, whereas it was absent in HC. The viral load in urine and plasma from the MS cohort increased over time, mostly pronounced in natalizumab-treated patients, whereas it persisted in HC. The archetypal NCCR was detected in all positive urine, whereas mutations were observed in plasma-derived NCCRs resulting in a more neurotropic variant. The prevalence and miR-J1-5p copy number in MS urine and plasma dropped after treatment, whereas they remained similar in HC specimens. Viruria and miR-J1-5p expression did not correlate with anti-JCV index. In conclusion, analyzing JCPyV DNA and miR-J1-5p levels may allow monitoring JCPyV activity and predicting MS patients at risk of developing PML.

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JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

Journal of Clinical Medicine ◽

10.3390/jcm10091998 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1998

Author(s):

Robert Bonek ◽

Wojciech Guenter ◽

Robert Jałowiński ◽

Anna Karbicka ◽

Anna Litwin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Jc Virus ◽

Dimethyl Fumarate ◽

Risk Category ◽

Seroprevalence Rate ◽

Immunomodulatory Drugs ◽

Cross Sectional ◽

Treatment Type ◽

Multiple Sclerosis Patients ◽

The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

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Cross-Sectional Analysis of Peripheral Blood Mononuclear Cells in Lymphopenic and Non-lymphopenic Relapsing-Remitting Multiple Sclerosis Patients Treated with Dimethyl Fumarate.

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2021.103003 ◽

2021 ◽

pp. 103003

Author(s):

Chieh-Hsin Lee ◽

Bei Jiang ◽

Maryam Nakhaei-Nejad ◽

David Barilla ◽

Gregg Blevins ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mononuclear Cells ◽

Dimethyl Fumarate ◽

Peripheral Blood Mononuclear ◽

Cross Sectional ◽

Relapsing Remitting ◽

Blood Mononuclear Cells ◽

Multiple Sclerosis Patients ◽

Sectional Analysis ◽

Relapsing Remitting Multiple Sclerosis

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Effect of tobacco use on disease activity and DMT discontinuation in multiple sclerosis patients treated with dimethyl fumarate or fingolimod

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217320959815 ◽

2020 ◽

Vol 6 (4) ◽

pp. 205521732095981

Author(s):

Carrie M Hersh ◽

Haleigh Harris ◽

Malissa Ayers ◽

Devon Conway

Keyword(s):

Multiple Sclerosis ◽

Risk Factor ◽

Clinical Practice ◽

Disease Activity ◽

Tobacco Use ◽

Dimethyl Fumarate ◽

Tobacco Exposure ◽

Disease Modifying Therapy ◽

Patient Reported ◽

Multiple Sclerosis Patients

Background Tobacco exposure is a modifiable risk factor for multiple sclerosis (MS). Studies evaluating the relationship between tobacco, disease activity, and disease modifying therapy (DMT) persistence yielded conflicting results. We sought to address this issue with data from clinical practice. Objective To compare 24-month disease outcomes in tobacco versus non-tobacco users treated with dimethyl fumarate (DMF) or fingolimod (FTY) in clinical practice. Methods We retrospectively identified 659 MS patients treated with DMF or FTY, stratified by patient-reported tobacco use. DMT discontinuation and measures of disease activity at 24 months were assessed using propensity score (PS) weighting. Outcome estimates were calculated as tobacco vs non-tobacco use. Results 164 tobacco users (DMF n = 101; FTY n = 63) and 495 non-tobacco users (DMF n = 294; FTY n = 201) were identified. Tobacco (39.4%) and non-tobacco (34.4%) users were equally likely to discontinue DMT (OR = 1.17, 95% CI 0.79, 1.75), but tobacco users discontinued therapy earlier (HR = 1.53, 95% CI 1.06, 2.43). There were no differences in ARR (rate ratio = 1.39, 95% CI 0.97, 1.96). However, tobacco users had decreased odds of NEDA-2 (OR = 0.61, 95% CI 0.44, 0.83). Conclusion Our findings suggest that tobacco is a negative risk factor for inflammatory disease activity and earlier DMF and FTY discontinuation.

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Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217320918619 ◽

2020 ◽

Vol 6 (2) ◽

pp. 205521732091861 ◽

Cited By ~ 1

Author(s):

Guy Buckle ◽

Daniel Bandari ◽

Jeffrey Greenstein ◽

Mark Gudesblatt ◽

Bhupendra Khatri ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Confidence Interval ◽

Cd8 T Cells ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Dimethyl Fumarate ◽

T Cell Subsets ◽

Routine Practice ◽

Patients At Risk

Background In patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia. Objective We investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate in routine practice. Methods Lymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6‐month intervals following dimethyl fumarate initiation. Results Charts of 483 patients were abstracted and 476 patients included in the analysis. Mean baseline absolute lymphocyte count (2.23 × 109/l) decreased by ∼39% (95% confidence interval: –41.1 to –37.2) by month 6 and 44% (95% confidence interval: –46.6 to –42.1) by month 12. CD4+ and CD8+ T-cell subsets strongly correlated with absolute lymphocyte count, with greater decreases from baseline to 6 months vs 6–12 months, and in CD8+ vs CD4+ T cells. Prior natalizumab was not a risk factor for lymphopenia. Conclusion Dimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia.

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Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center

Multiple Sclerosis Journal ◽

10.1177/1352458517709956 ◽

2017 ◽

Vol 24 (7) ◽

pp. 942-950 ◽

Cited By ~ 12

Author(s):

Kyle Smoot ◽

Kateri J Spinelli ◽

Tamela Stuchiner ◽

Lindsay Lucas ◽

Chiayi Chen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Duration ◽

Community Health Center ◽

Dimethyl Fumarate ◽

Clinical Relapse ◽

Disease Modifying Therapy ◽

Magnetic Resonance Imaging Mri ◽

Multiple Sclerosis Patients ◽

Previous Disease ◽

Relapsing Multiple Sclerosis

Background: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. Objective: To track DMF patients’ tolerability, disease progression, and lymphopenia. Methods: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. Results: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-β (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). Conclusion: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

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