Contributions
Abstract: P924
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Anti-JC virus (JCV) antibodies are a risk factor for progressive multifocal leucoencephalopathy (PML) in natalizumab (NTZ)-treated patients. In anti-JCV antibody positive patients without prior immunosuppressant use, the level of anti-JCV antibody response (“index”) correlates with PML risk and allows improved risk stratification. Whether NTZ treatment affects index stability has been debated. No randomised, placebo (PBO)-controlled data have previously been assessed.
Objectives: To evaluate longitudinal index stability in patients treated with NTZ or PBO over 2 years in the ASCEND study.
Methods: ASCEND was a randomised, double-blind, PBO-controlled phase 3 trial conducted in patients with secondary progressive multiple sclerosis. Patients were tested for anti-JCV antibodies at baseline (BL) and every 24 weeks. Investigators were blinded to results until study completion. Patients with index values at BL, week 48, and week 96 were included in this analysis. Mean index changes from BL and proportions of patients with index ≤0.4, >0.4 to ≤0.9, >0.9 to ≤1.5, and >1.5 at each time point were evaluated for each treatment arm. The within-patient variability of index was assessed based on the changes between visits.
Results: In ASCEND, 889 patients were randomised (PBO, 449; NTZ, 440); 662 had index data at all 3 time points (PBO, 320; NTZ, 342). Changes in mean index value from BL to week 48 (PBO, −0.12; NTZ, −0.19) and week 96 (PBO, −0.12; NTZ, −0.20) were small. Proportions of patients in each index group were similar in the 2 treatment groups between BL and week 96 (index ≤0.4: PBO, 44.4%−45.0%; NTZ, 41.6%−43.7%; index >0.4 to ≤0.9: PBO, 12.5%−13.8%; NTZ, 12.9%−16.1%; index >0.9 to ≤1.5: PBO, 7.2%−10.3%; NTZ, 10.0%−11.1%). At BL, 35.3% of PBO patients and 34.8% of NTZ patients had index >1.5; this proportion was lower in both groups at week 48 (PBO, 31.3%; NTZ, 30.1%) and week 96 (PBO, 32.8%; NTZ, 31.6%) with proportions similar between groups at each time point. Within-patient index variability was low: the majority of patients experienced ≤0.5 increase in index between visits (PBO, 90.3%; NTZ, 88.0%), and few patients exhibited an index increase >1 (PBO, 5.0%; NTZ, 3.5%).
Conclusions: This analysis in a PBO-controlled trial population provides robust evidence that NTZ treatment is not associated with changes in index over time. The stability of index regardless of NTZ treatment supports the use of index for individualised patient management.
Disclosure: Supported by Biogen.
LM, IC, ZR, P-RH: employees of and may hold stock and/or stock options in Biogen.
TB: received personal compensation for consulting services and/or speaking at scientific symposia from Allergan, Biogen, Bionorica, Celgene, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, Teva.
RK: received support from the UK National Institute of Health Research UCL/H Biomedical Research Centre and personal compensation for consultancies, lectures, participation in advisory boards, and/or support for travel to medical meetings from Actelion, Biogen, Genzyme, Novartis, Roche, Teva.
H-PH: received personal compensation for consulting services and/or speaking at scientific symposia from Bayer Healthcare, Biogen, Celegene Receptos, GeNeuro, Genzyme, Merck Serono, Novartis, Octapharma, Roche, Teva
Abstract: P924
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Anti-JC virus (JCV) antibodies are a risk factor for progressive multifocal leucoencephalopathy (PML) in natalizumab (NTZ)-treated patients. In anti-JCV antibody positive patients without prior immunosuppressant use, the level of anti-JCV antibody response (“index”) correlates with PML risk and allows improved risk stratification. Whether NTZ treatment affects index stability has been debated. No randomised, placebo (PBO)-controlled data have previously been assessed.
Objectives: To evaluate longitudinal index stability in patients treated with NTZ or PBO over 2 years in the ASCEND study.
Methods: ASCEND was a randomised, double-blind, PBO-controlled phase 3 trial conducted in patients with secondary progressive multiple sclerosis. Patients were tested for anti-JCV antibodies at baseline (BL) and every 24 weeks. Investigators were blinded to results until study completion. Patients with index values at BL, week 48, and week 96 were included in this analysis. Mean index changes from BL and proportions of patients with index ≤0.4, >0.4 to ≤0.9, >0.9 to ≤1.5, and >1.5 at each time point were evaluated for each treatment arm. The within-patient variability of index was assessed based on the changes between visits.
Results: In ASCEND, 889 patients were randomised (PBO, 449; NTZ, 440); 662 had index data at all 3 time points (PBO, 320; NTZ, 342). Changes in mean index value from BL to week 48 (PBO, −0.12; NTZ, −0.19) and week 96 (PBO, −0.12; NTZ, −0.20) were small. Proportions of patients in each index group were similar in the 2 treatment groups between BL and week 96 (index ≤0.4: PBO, 44.4%−45.0%; NTZ, 41.6%−43.7%; index >0.4 to ≤0.9: PBO, 12.5%−13.8%; NTZ, 12.9%−16.1%; index >0.9 to ≤1.5: PBO, 7.2%−10.3%; NTZ, 10.0%−11.1%). At BL, 35.3% of PBO patients and 34.8% of NTZ patients had index >1.5; this proportion was lower in both groups at week 48 (PBO, 31.3%; NTZ, 30.1%) and week 96 (PBO, 32.8%; NTZ, 31.6%) with proportions similar between groups at each time point. Within-patient index variability was low: the majority of patients experienced ≤0.5 increase in index between visits (PBO, 90.3%; NTZ, 88.0%), and few patients exhibited an index increase >1 (PBO, 5.0%; NTZ, 3.5%).
Conclusions: This analysis in a PBO-controlled trial population provides robust evidence that NTZ treatment is not associated with changes in index over time. The stability of index regardless of NTZ treatment supports the use of index for individualised patient management.
Disclosure: Supported by Biogen.
LM, IC, ZR, P-RH: employees of and may hold stock and/or stock options in Biogen.
TB: received personal compensation for consulting services and/or speaking at scientific symposia from Allergan, Biogen, Bionorica, Celgene, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, Teva.
RK: received support from the UK National Institute of Health Research UCL/H Biomedical Research Centre and personal compensation for consultancies, lectures, participation in advisory boards, and/or support for travel to medical meetings from Actelion, Biogen, Genzyme, Novartis, Roche, Teva.
H-PH: received personal compensation for consulting services and/or speaking at scientific symposia from Bayer Healthcare, Biogen, Celegene Receptos, GeNeuro, Genzyme, Merck Serono, Novartis, Octapharma, Roche, Teva