High cumulative <scp>JC</scp> virus seroconversion rate during long‐term use of natalizumab

Vennegoor, Anke; Rossum, J.A. van; Leurs, Cyra E.; Wattjes, Mike P.; Rispens, Theo; Murk, Jean Luc; Uitdehaag, Bernard M. J.; Killestein, Joep

doi:10.1111/ene.12988

Cited by 46 publications

(33 citation statements)

References 22 publications

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“…In the present study, we could not confirm previous reports on higher seroconversion rates and rising anti-JCV antibody indices in MS patients treated with natalizumab [12, 14, 22]. Although we observed a numerically higher rate of serostatus change in natalizumab-treated patients compared to patients receiving other or no DMT, this difference was not statistically significant.…”

Section: Discussioncontrasting

confidence: 99%

“…However, we did not intend to study anti-JCV antibody frequency; and different frequencies most likely do not impact on longitudinal evolution of antibody indices neither in the initially seronegative nor seropositive group. It cannot be excluded that the lower rate of seroconversion in the natalizumab-treated cohort (compared to other recent reports [12, 14, 22]) is due to the low number of patients in this treatment group.…”

Section: Discussioncontrasting

confidence: 58%

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Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

et al. 2017

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BackgroundRisk of natalizumab-related progressive multifocal leukoencephalopathy is associated with the presence of anti-JC-virus (JCV) antibodies.ObjectiveTo investigate the longitudinal evolution of anti-JCV antibody index and to determine the predictive value of baseline anti-JCV antibody index for long-term stability of anti-JCV antibody status.MethodsMS patients from the MS centre of Medical University of Innsbruck, who had serum sampling for a time period of 4–6 years at intervals of 6±3 months, were included in this retrospective, longitudinal study. Anti-JCV antibody serological status and index were determined by 2-step second-generation anti-JCV antibody assay.Results154 patients were included in this study. Median follow-up time was 63.7 months, with median 11 samples available per patient. At baseline, 111 (72.1%) patients were anti-JCV antibody positive. Baseline anti-JCV antibody index significantly correlated with age (R = 0.22, p = 0.005); there was no difference with respect to sex, disease duration or previously used disease-modifying treatment. During follow-up anti-JCV antibody status changed from negative to positive or vice versa in 17% of patients. In seronegative patients at baseline, baseline anti-JCV antibody index was significantly lower in those remaining seronegative at follow-up compared to those converting to seropositivity (median 0.16 vs. 0.24, p = 0.002). In seropositive patients at baseline, index was higher in those remaining seropositive compared to those reverting to seronegativity (2.6 vs. 0.45, p<10−7). Baseline anti-JCV antibody index >0.90 predicted stable positive serostatus (sensitivity 88.7%, specificity 96.5%) and <0.20 stable negative serostatus (sensitivity 61.3%, specificity 97.6%).ConclusionsAnti-JCV antibody index remained relatively stable over 6-year follow-up with annual serostatus change of ~3%. Baseline anti-JCV antibody index predicted stable negative and stable positive JCV serostatus.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 58%

Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

et al. 2017

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“…These high JCV seroconversion rates are likely due to the main use of Gen1 to measure the first samples whereas the second samples were all analysed with Gen2. Indeed, the positive rate of seroconversion among patients measured twice with Gen2 (8Á1%) in our study was similar to this published by Trampe et al [16] and Vennegoor et al [19] only using Gen1 or by Aladro et al [20] only using Gen2. Then, although the agreement between both techniques is good, maybe it is not enough for not detecting differences between the results of both test.…”

Section: Discussionsupporting

confidence: 92%

“…The seropositivity rate (58Á2%) for anti-JCV antibodies in this Spanish cohort was within the previously reported range (50-60%) [14][15][16][17][18][19][20] using two-step ELISA, regardless of whether the patients with MS were under natalizumab treatment or not. According to most previous studies [14][15][16][17]21,22], our seropositivity rate increased with age, but contrary to other ones [14][15][16][17], it was not higher in males (Table 2), as other studied also found [21,[23][24][25][26].…”

Section: Discussionsupporting

confidence: 86%

Study of the anti‐JCV antibody levels in a Spanish multiple sclerosis cohort

Domínguez-Mozo

Rus

Santiago

et al. 2017

Eur J Clin Investigation

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“…The annual rate of seroconversion from JCV antibody negative to positive varies in the literature, and it seems likely that therapy with natalizumab increases the seroconversion rate 34,51,69. It is therefore prudent to periodically repeat JCV antibody testing in patients who are initially negative.…”

Section: The Use Of Natalizumab In Clinical Practicementioning

confidence: 99%

The use of natalizumab for multiple sclerosis

Brandstadter¹,

Sand²

2017

NDT

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Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability. The leading safety concern with natalizumab is its association with progressive multifocal leukoencephalopathy (PML), a rare brain infection typically seen only in severely immunocompromised patients caused by reactivation of the John Cunningham virus (JCV). Careful analysis of risk factors for PML in natalizumab-treated MS patients, specifi-cally the presence of anti-JCV antibodies, has led to risk mitigation strategies to improve safety. Additional biomarkers are under investigation to further aid risk stratification. Natalizumab’s high efficacy and favorable tolerability profile have led to a broad use by MS physicians, as both first-and second-line treatments. This review discusses the natalizumab efficacy, safety, and tolerability and finishes with pragmatic considerations regarding its use in clinical practice.

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High cumulative JC virus seroconversion rate during long‐term use of natalizumab

Cited by 46 publications

References 22 publications

Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study

Study of the anti‐JCV antibody levels in a Spanish multiple sclerosis cohort

The use of natalizumab for multiple sclerosis

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