Contributions
Abstract: P1213
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod has demonstrated efficacy in patients with highly active relapsing−remitting multiple sclerosis (MS). Based on estimates, up to 20% of patients currently being treated with fingolimod received prior natalizumab treatment. The main reason for stopping natalizumab treatment is the risk of progressive multifocal leukoencephalopathy (PML).
Objective: To evaluate the effectiveness and safety of fingolimod in patients with MS who switched from natalizumab to fingolimod.
Methods: TRANSITION was a 2-year, observational, single-cohort study in patients with relapsing MS who received the last natalizumab infusion within 12 months of enrolment and started fingolimod at study entry or within the past 12 months. Fingolimod effectiveness was measured by the annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score. The safety profile was assessed by incidence of adverse events (AEs) and serious AEs (SAEs). Exposure-adjusted incidence rates (IRs) per 100 patient-years for AEs were also recorded.
Results: In total 637 patients were studied. At baseline (BL), the mean age was 42 years, 71.9% were women and mean disease duration was 10.5 years. BL EDSS was 3.35; 83.5% patients were John Cunningham virus antibody positive (JCV+). The primary reasons for switching were JCV+ (68.3%) and >2 years of natalizumab treatment (30.3%). The median exposure to natalizumab was 924.0 days and mean washout period before starting fingolimod was 14.5 weeks. The ARR declined from 0.46 in the 2 years before study (including washout) to 0.27 on study. The percentage of patients with relapses increased with increase in natalizumab washout period: from 4.5% (≤8 weeks) to 31.9% (>16 weeks). The mean change from BL in EDSS on study was 0.27. AEs and SAEs were reported in 72.8% and 12.7% patients, respectively. No SAE cases of opportunistic infections including PML were reported. Exposure-adjusted IRs (95% CI) for AEs were reduced with fingolimod treatment over 2 years: 172.3 (153.7; 190.9) at ≤180 days, 59.5 (45.67; 73.36) at >180-≤360 days and 30.1 (22.29; 37.93) at >360 days.
Conclusions: Fingolimod was effective in controlling clinical disease activity in patients switched from natalizumab. A treatment gap of ≤8 weeks results in lowest risk of relapse. No new safety signals emerged. The IRs of AEs decreased with increasing treatment duration. The benefit−risk profile supports the use of fingolimod in patients with MS switching from natalizumab to reduce PML risk.
Disclosure:
Funding source: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Helmut Butzkueven has received compensation for serving as a consultant or speaker for, or he or the institution he works for has received research support from Biogen Idec, Novartis, Merck Serono and Sanofi Genzyme; he is on the editorial board of Multiple Sclerosis International and Multiple Sclerosis and Related Disorders; and he has received project grants from the National Health and Medical Research Council (NHMRC), Australian Research Council Linkage Grant RG and National MS Society (USA).
Belinda Weller has received compensation for consulting, speaking and travel from Novartis, Genzyme, Biogen, Merck, Roche and Teva.
Paul Steven Giacomini has received honoraria for speaking, consulting, and advisory board participation from Allergan, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Roche and Teva Neuroscience. He has received research support from Biogen Idec and Teva Neuroscience; he has been a consultant for NeuroRx Research, an imaging Contract Research Organization; and he has acted as a principal investigator or subinvestigator for clinical trials for Alexion, Bayer HealthCare, Biogen Idec, Elan, EMD Serono, GlaxoSmithKline, Novartis, Ono, Roche Genentech, Sanofi Aventis and Teva Neuroscience.
Stanley Cohan has received speaking honoraria, served on steering committees or advisory boards and has received research support from Biogen, Novartis, SanofiGenzyme, Roche, Acorda, Opexa, MedDay and Mallinckrodt.
Tjalf Ziemssen has received personal compensation for serving on advisory boards, trial steering committees and data and safety monitoring committees, as well as for scientific talks and project support from: Bayer HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis, Synthon and Teva.
Harald Kropshofer, Scott Bellman, Daniel Sienkiewicz, Alfred Kubong Mbah, Yvonne Geissbuehler, Davorka Tomic and Diego Silva are employees of Novartis.
Maria Trojano has served on scientific advisory boards for Biogen Idec, Novartis, Genzyme, Roche and Merck Serono; she has received speaker honoraria from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono, Teva, Almirall and Novartis; and she has received research grants from BiogenIdec, MerckSerono and Novartis.
Abstract: P1213
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod has demonstrated efficacy in patients with highly active relapsing−remitting multiple sclerosis (MS). Based on estimates, up to 20% of patients currently being treated with fingolimod received prior natalizumab treatment. The main reason for stopping natalizumab treatment is the risk of progressive multifocal leukoencephalopathy (PML).
Objective: To evaluate the effectiveness and safety of fingolimod in patients with MS who switched from natalizumab to fingolimod.
Methods: TRANSITION was a 2-year, observational, single-cohort study in patients with relapsing MS who received the last natalizumab infusion within 12 months of enrolment and started fingolimod at study entry or within the past 12 months. Fingolimod effectiveness was measured by the annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score. The safety profile was assessed by incidence of adverse events (AEs) and serious AEs (SAEs). Exposure-adjusted incidence rates (IRs) per 100 patient-years for AEs were also recorded.
Results: In total 637 patients were studied. At baseline (BL), the mean age was 42 years, 71.9% were women and mean disease duration was 10.5 years. BL EDSS was 3.35; 83.5% patients were John Cunningham virus antibody positive (JCV+). The primary reasons for switching were JCV+ (68.3%) and >2 years of natalizumab treatment (30.3%). The median exposure to natalizumab was 924.0 days and mean washout period before starting fingolimod was 14.5 weeks. The ARR declined from 0.46 in the 2 years before study (including washout) to 0.27 on study. The percentage of patients with relapses increased with increase in natalizumab washout period: from 4.5% (≤8 weeks) to 31.9% (>16 weeks). The mean change from BL in EDSS on study was 0.27. AEs and SAEs were reported in 72.8% and 12.7% patients, respectively. No SAE cases of opportunistic infections including PML were reported. Exposure-adjusted IRs (95% CI) for AEs were reduced with fingolimod treatment over 2 years: 172.3 (153.7; 190.9) at ≤180 days, 59.5 (45.67; 73.36) at >180-≤360 days and 30.1 (22.29; 37.93) at >360 days.
Conclusions: Fingolimod was effective in controlling clinical disease activity in patients switched from natalizumab. A treatment gap of ≤8 weeks results in lowest risk of relapse. No new safety signals emerged. The IRs of AEs decreased with increasing treatment duration. The benefit−risk profile supports the use of fingolimod in patients with MS switching from natalizumab to reduce PML risk.
Disclosure:
Funding source: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Helmut Butzkueven has received compensation for serving as a consultant or speaker for, or he or the institution he works for has received research support from Biogen Idec, Novartis, Merck Serono and Sanofi Genzyme; he is on the editorial board of Multiple Sclerosis International and Multiple Sclerosis and Related Disorders; and he has received project grants from the National Health and Medical Research Council (NHMRC), Australian Research Council Linkage Grant RG and National MS Society (USA).
Belinda Weller has received compensation for consulting, speaking and travel from Novartis, Genzyme, Biogen, Merck, Roche and Teva.
Paul Steven Giacomini has received honoraria for speaking, consulting, and advisory board participation from Allergan, Bayer HealthCare, Biogen Idec, EMD Serono, Genzyme, Novartis, Roche and Teva Neuroscience. He has received research support from Biogen Idec and Teva Neuroscience; he has been a consultant for NeuroRx Research, an imaging Contract Research Organization; and he has acted as a principal investigator or subinvestigator for clinical trials for Alexion, Bayer HealthCare, Biogen Idec, Elan, EMD Serono, GlaxoSmithKline, Novartis, Ono, Roche Genentech, Sanofi Aventis and Teva Neuroscience.
Stanley Cohan has received speaking honoraria, served on steering committees or advisory boards and has received research support from Biogen, Novartis, SanofiGenzyme, Roche, Acorda, Opexa, MedDay and Mallinckrodt.
Tjalf Ziemssen has received personal compensation for serving on advisory boards, trial steering committees and data and safety monitoring committees, as well as for scientific talks and project support from: Bayer HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis, Synthon and Teva.
Harald Kropshofer, Scott Bellman, Daniel Sienkiewicz, Alfred Kubong Mbah, Yvonne Geissbuehler, Davorka Tomic and Diego Silva are employees of Novartis.
Maria Trojano has served on scientific advisory boards for Biogen Idec, Novartis, Genzyme, Roche and Merck Serono; she has received speaker honoraria from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono, Teva, Almirall and Novartis; and she has received research grants from BiogenIdec, MerckSerono and Novartis.