Contributions
Abstract: P613
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Among patients treated with natalizumab for multiple sclerosis, the presence of serum anti-JCV antibodies predicts development of progressive multifocal leukoencephalopathy (PML). However, the association between prolonged natalizumab therapy, rising antibody titres and their relevance to increased PML risk is poorly understood.
Objectives: A retrospective, longitudinal audit was undertaken to investigate effects of natalizumab on serum anti-JCV antibody titres over time.
Aims: To determine whether natalizumab treatment length increases risks of seroconversion.
Methods: Among 154 patients treated with natalizumab for MS, we evaluated sequential changes in anti-JCV antibody titres from baseline using the STRATIFY JCVTM DxSelectTM assay.
Results: No baseline differences in mean antibody titres were identified between patients seroconverting or remaining seronegative (0.178±0.0161 vs. 0.208±0.0157, p=0.417 respectively). However, seroconverting patients showed rising antibody titres early in the follow-up period, with mean antibody titres that were consistently and significantly higher than those remaining seronegative (p< 0.01). Antibody titres remained stable over time with prolonged natalizumab use among all baseline-seronegative patients and those that seroconverted. However, seroconverting patients were treated for significantly longer with natalizumab compared to those remaining seronegative (44.9±3.61 vs. 32.1±2.05 months, p=0.005). There were no gender differences in anti-JCV titres at baseline (0.503±0.0855 male vs. 0.555±0.214 female, p=0.97) or over time. No significant differences were observed in baseline antibody titres between age groups, with no age group more likely to seroconvert (p=0.445).
Conclusions: Contrary to previous publications, anti-JCV antibody titres remained stable among baseline-seronegative patients treated with natalizumab despite established associations between high antibody titres, treatment length, and PML development. Our results suggest certain patients demonstrate early changes in anti-JCV titres with natalizumab leading to seroconversion, indicating variability in the immune predisposition to seroconvert. This warrants further investigation to better understand the complex interplay which exists between viral, host and environmental factors that link seroconversion to PML development.
Disclosure: Piriyankan Ananthavarathan: nothing to disclose
Daniel White: nothing to disclose
Sharon Letissier: nothing to disclose
Ghaniah Hassan-Smith: nothing to disclose
Sonia Kumari: nothing to disclose
Niraj Mistry has participated in advisory boards for Roche and Novartis and has been sponsored for conference attendance by Novartis, Biogen, Bayer, Teva and Roche.
Gordon Mazibrada has participated in consultancy work and their department has received education and service development funding from Merck Serono Vich, Novartis, Biogen, Bayer, Teva and Roche
John Woolmore has participated in consultancy work and their department has received education and service development funding from Merck Serono Vich, Novartis, Biogen, Bayer, Teva and Roche
Abstract: P613
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Among patients treated with natalizumab for multiple sclerosis, the presence of serum anti-JCV antibodies predicts development of progressive multifocal leukoencephalopathy (PML). However, the association between prolonged natalizumab therapy, rising antibody titres and their relevance to increased PML risk is poorly understood.
Objectives: A retrospective, longitudinal audit was undertaken to investigate effects of natalizumab on serum anti-JCV antibody titres over time.
Aims: To determine whether natalizumab treatment length increases risks of seroconversion.
Methods: Among 154 patients treated with natalizumab for MS, we evaluated sequential changes in anti-JCV antibody titres from baseline using the STRATIFY JCVTM DxSelectTM assay.
Results: No baseline differences in mean antibody titres were identified between patients seroconverting or remaining seronegative (0.178±0.0161 vs. 0.208±0.0157, p=0.417 respectively). However, seroconverting patients showed rising antibody titres early in the follow-up period, with mean antibody titres that were consistently and significantly higher than those remaining seronegative (p< 0.01). Antibody titres remained stable over time with prolonged natalizumab use among all baseline-seronegative patients and those that seroconverted. However, seroconverting patients were treated for significantly longer with natalizumab compared to those remaining seronegative (44.9±3.61 vs. 32.1±2.05 months, p=0.005). There were no gender differences in anti-JCV titres at baseline (0.503±0.0855 male vs. 0.555±0.214 female, p=0.97) or over time. No significant differences were observed in baseline antibody titres between age groups, with no age group more likely to seroconvert (p=0.445).
Conclusions: Contrary to previous publications, anti-JCV antibody titres remained stable among baseline-seronegative patients treated with natalizumab despite established associations between high antibody titres, treatment length, and PML development. Our results suggest certain patients demonstrate early changes in anti-JCV titres with natalizumab leading to seroconversion, indicating variability in the immune predisposition to seroconvert. This warrants further investigation to better understand the complex interplay which exists between viral, host and environmental factors that link seroconversion to PML development.
Disclosure: Piriyankan Ananthavarathan: nothing to disclose
Daniel White: nothing to disclose
Sharon Letissier: nothing to disclose
Ghaniah Hassan-Smith: nothing to disclose
Sonia Kumari: nothing to disclose
Niraj Mistry has participated in advisory boards for Roche and Novartis and has been sponsored for conference attendance by Novartis, Biogen, Bayer, Teva and Roche.
Gordon Mazibrada has participated in consultancy work and their department has received education and service development funding from Merck Serono Vich, Novartis, Biogen, Bayer, Teva and Roche
John Woolmore has participated in consultancy work and their department has received education and service development funding from Merck Serono Vich, Novartis, Biogen, Bayer, Teva and Roche