Anti-JCV serology during natalizumab treatment: Review and meta-analysis of 17 independent patient cohorts analyzing anti-John Cunningham polyoma virus sero-conversion rates under natalizumab treatment and differences between technical and biological sero-converters

Schwab, Nicholas; Schneider‐Hohendorf, Tilman; Hoyt, Tammy; Groß, Catharina C.; Meuth, Sven G.; Klotz, Luisa; Foley, John; Wiendl, Heinz

doi:10.1177/1352458517728814

Cited by 31 publications

(37 citation statements)

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“…Due to the high number of Natalizumab‐treated patients in our cohort—because patients treated with Natalizumab were best accessible for short‐term blood withdrawal receiving monthly infusions—prevalence of JCV was approximately 52%, slightly lower than previously published data would show (Bozic et al, ; Olsson et al, ; Outteryck et al, ; Warnke et al, ). Anti‐JCV antibody status and index showed a significant correlation with age, as it was found in other cohorts as well (Hegen et al, ; Schwab et al, ).…”

Section: Discussionsupporting

confidence: 69%

“…There was no patient switching from negative to continuously high positive status, i.e., reflecting a new infection with JCV. This observation suggests that the rate of true seroconverters per year may be lower than discussed in previous publications (Schwab et al, ). We chose a study cohort of approximately 110 patients based on a power calculation assuming a seroconversion rate of 3% per year, as previously described (Hegen et al, ).…”

Section: Discussionmentioning

confidence: 45%

“…Additionally, we wanted to confirm development of anti‐JCV antibody index values over time in a prospective setting, which has been well described in retrospective analyses (Hegen et al, ; Schwab et al, ).…”

Section: Introductionmentioning

confidence: 93%

“…Most patients who eventually developed PML showed an index value of 1.5 or higher, thus anti‐JCV antibody positive patients can be stratified in a low and high PML‐risk group by anti‐JCV antibody index (Ho et al, ). Furthermore, longitudinal observations of multiple JCV testing showed that most patients present stable anti‐JCV antibody status and index values over years, although seroconvertion rates of 5%–33% per year have been described (reviewed by Schwab et al, ). In this context one has to distinguish between patients who fluctuate around the cut‐off index of the ELISA test, by that converting and reverting between anti‐JCV antibody negative and positive although showing index values within a narrow range, and patients who experience a new infection with JCV by converting from negative to persistently positive anti‐JCV antibody index values (Alroughani et al, ; Campagnolo, Ho, & Patel, ; Donovan & LaGanke, ; Hegen et al, ; Plavina et al, ; Vennegoor et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

et al. 2019

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Introduction Determination of antibodies against the John Cunningham virus (JCV) is an important tool for risk stratification in Natalizumab‐treated multiple sclerosis (MS) patients. Six‐monthly testing has been suggested for anti‐JCV antibody negative patients and patients with low antibody index in order to detect changes of serostatus. We conducted a prospective study with predefined testing intervals in order to investigate the predictability of anti‐JCV antibody status and the intervals for repetitive testing. Methods Our study included 109 patients at the MS Clinic of the Departments of Neurology, Medical Universities of Innsbruck and Salzburg. Blood withdrawals were performed at five time points: baseline, month 1, 3, 6, and 12. Patients’ sera were sent to Unilabs, Copenhagen, Denmark, where anti‐JCV antibodies were tested by a two‐step enzyme‐linked immunosorbent assay. Qualitative (negative/positive) and quantitative results (anti‐JCV antibody index) were used for statistical analyses. Results In our cohort, 52.3% of the patients were positive for anti‐JCV antibodies at baseline, with a significant correlation with age, but no association with sex or prior disease‐modifying therapy. Seven patients converted and reverted from negative to positive status and vice versa around the cut‐off index of 0.4, but no patient showed a permanent seroconversion from negative to highly positive anti‐JCV antibody status. Conclusion Long‐term anti‐JCV antibody status, including seroconverters/‐reverters around the cut‐off index, is highly predictable by testing three times within short intervals, however, we cannot suggest clearly defined intervals for repetitive testing. The rate of real seroconverters, i.e., new infections with JCV, per year seems lower than previously described.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 45%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

et al. 2019

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“…For natalizumab, which carries the highest risk (9), patients are tested for JCV antibodies using the STRATIFY JCV assay (17,18). However, the specificity of this test is low because JCV is ubiquitous in the general population (18,19) and even JCV-negative patients are not free of risk since ∼11% will seroconvert and thus be in the higher risk group (20). Confounding the risk decision process for the clinician and patient is natalizumab's high efficacy (21,22), leading many JCV-positive patients to take it despite the risk of PML.…”

Section: Introductionmentioning

confidence: 99%

Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy

Eis

Bruno²,

Richmond³

et al. 2020

Front. Neurol.

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Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

et al. 2023

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ImportanceProposed biosimilar natalizumab (biosim-NTZ) PB006 is the first biosimilar monoclonal antibody therapy developed for multiple sclerosis (MS) treatment.ObjectiveTo evaluate matching efficacy, safety, and immunogenicity between biosim-NTZ and reference natalizumab (ref-NTZ) in patients with relapsing-remitting MS (RRMS).Design, Setting, and ParticipantsThe Antelope trial was a phase 3, parallel-group, randomized, active-controlled study, conducted between October 2019 and March 2021, with last patient follow-up visit on August 23, 2021. The study took place in 48 centers in 7 countries. Of 531 patients with RRMS aged 18 to 60 years screened, 266 were excluded before randomization in line with study criteria. Eligible participants had 1 or more documented relapse within the previous year and either 1 or more gadolinium-enhancing T1-weighted or 9 or more T2-weighted brain lesions, Kurtzke Expanded Disability Status Scale score of 0 to 5.0 (inclusive), and John Cunningham virus index of 1.5 or less at screening. One patient withdrew consent before dosing.InterventionsIntravenous infusions every 4 weeks of biosim-NTZ, 300 mg, or ref-NTZ, 300 mg (1:1 randomization), from week 0 to week 44 (end-of-study visit: week 48). At week 24, the ref-NTZ group was rerandomized and 30 patients were switched to biosim-NTZ for the remainder of the study.Main Outcomes and MeasuresThe primary end point was the cumulative number of new active lesions on magnetic resonance imaging (new gadolinium-enhancing T1-weighted lesions and new/enlarging T2-weighted lesions without double counting) over 24 weeks. Additional end points included further magnetic resonance imaging parameters, annualized relapse rate, and Kurtzke Expanded Disability Status Scale score. Safety, tolerability, and immunogenicity assessments included adverse events, laboratory evaluations, and positivity for anti–John Cunningham virus antibodies and antinatalizumab antibodies.ResultsA total of 264 participants (mean [SD] age, 36.7 [9.38] years; 162 [61.4%] female) received treatment with biosim-NTZ (n = 131) or ref-NTZ (n = 133). At week 24, the model-based mean difference in cumulative number of new active lesions between biosim-NTZ and ref-NTZ treatment groups was 0.17 (least square means [SE]: biosim-NTZ, 0.34 [0.34]; ref-NTZ, 0.45 [0.28]; 95% CI, –0.61 to 0.94 within the prespecified margins of ±2.1). No significant differences between treatment groups were observed across secondary efficacy end points, safety, tolerability, or immunogenicity assessments.Conclusions and RelevanceBiosim-NTZ matched ref-NTZ in efficacy, safety, and immunogenicity for patients with RRMS in the tested setting. This phase 3 trial supports proposed biosim-NTZ as a biosimilar alternative to ref-NTZ for treating RRMS.Trial RegistrationClinicalTrials.gov Identifier: NCT04115488

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Anti-JCV serology during natalizumab treatment: Review and meta-analysis of 17 independent patient cohorts analyzing anti-John Cunningham polyoma virus sero-conversion rates under natalizumab treatment and differences between technical and biological sero-converters

Cited by 31 publications

References 46 publications

Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

Conversion and reversion of anti‐John Cunningham virus antibody serostatus: A prospective study

Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

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