Contributions
Abstract: EP1704
Type: ePoster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: SELECTED (NCT01051349) was an open-label extension study that evaluated treatment with daclizumab beta (DAC BETA) for up to 6 additional years in patients with relapsing MS (RMS) who completed the randomized SELECT/SELECTION studies. A previous interim analysis of SELECTED showed that efficacy was maintained over 3 years of continuous treatment and adverse events (AEs) did not increase over time.
Objective: To report the long-term safety and efficacy outcomes in RMS patients treated with DAC BETA in SELECTED.
Methods: Patients who completed 1-2 years of treatment with DAC BETA in SELECT/SELECTION were eligible to receive open-label DAC BETA 150mg subcutaneous every 4 weeks for up to 6 more years in SELECTED. To consolidate extension studies, SELECTED was stopped early and patients transitioned to the open-label EXTEND (NCT01797965) study that also includes patients from DECIDE and OBSERVE.
Results: 90% (410/455) of patients who completed treatment in SELECT/SELECTION enrolled in SELECTED. The mean (median) time on treatment in SELECTED was 40.2 (45.1; range:0-66) months; 69% of patients received DAC BETA for >3 years, 39% for >4 years and 9% for >5 years. The incidence of AEs in Years 1, 2, 3, 4 and ≥5 was 60%, 60%, 57%, 56% and 51%. 87% of patients experienced an AE; 26%, a serious AE excluding MS relapse. Most patients (75%) had AEs that were mild/moderate in severity. There were no deaths during the study. Incidence of alanine transaminase and/or aspartate transaminase elevations >5x upper limit of normal was 9% and 6%, respectively.The adjusted annualised relapse rate (95%CI) in Years 1, 2, 3, 4 and ≥5 was 0.150 (0.111, 0.205), 0.122 (0.087, 0.170), 0.105 (0.074, 0.148), 0.133 (0.084, 0.211) and 0.087 (0.054, 0.140). The incidence of 24-week confirmed disability progression was low (17.4%) with a stable rate of occurrence over the study period. The mean numbers of new Gd+ and new/newly enlarging T2 hyperintense lesions occurred at rates similar to the reduced rates in SELECT/SELECTION. The percentage change in whole brain volume was −0.4%, −0.4%, −0.2%, −0.5%, −0.2% and 0.1% for Years 1, 2, 3, 4, 5 and 6, respectively.
Conclusions: Results from SELECTED extend those from SELECT/SELECTION and together show that the effects of DAC BETA on clinical and radiologic outcomes and the favourable benefit/risk profile of DAC BETA were sustained over up to ~8 years of treatment, with no new safety concerns identified in the SELECTED study population.
Disclosure:
R. Gold: consulting fees from Bayer HealthCare, Biogen, Novartis, Merck Serono, Sanofi-Aventis, and Teva; editor of Therapeutic Advances in Neurological Disorders; research support from Biogen, Genzyme, Merck Serono, Novartis, and Teva.
E.-W. Radue: speaker fees from Actelion, Basilea, Bayer HealthCare, Biogen, Merck Serono, and Novartis; research support from Actelion, Bayer HealthCare, Biogen, Merck Serono, and Novartis.
G. Giovannoni: advisory boards for AbbVie Inc., Almirall, Atara Bio, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi-Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis and Teva; co-editor in chief of Multiple Sclerosis and Related Disorders; research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono and Novartis.
K. Selmaj: consulting fees from Genzyme, Novartis, Ono, Roche, Synthon, and Teva; speaker fees from Biogen.
E. Havrdova: honoraria/research support from Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche and Teva; advisory boards for Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis and Roche; supported by the Czech Ministry of Education research project PROGRES Q27/LF1.
X. Montalban: speaker fees/travel expense reimbursement from and steering committee/advisory boards for Actelion, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck, Neurotec, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis, Teva, and Trophos.
D. Stefoski: consulting fees from Acorda, Biogen, Serono, and Teva Neuroscience; speaker fees from Acorda, Biogen, Elan, EMD Serono, and Teva Neuroscience; royalty payments of licensed drug from Acorda; research support from Biogen, Novartis, Pfizer, and Serono.
T. Sprenger: the University Hospital Basel (previous employer) and/or current (DKD Helios Klinik Wiesbaden) employer of TS received speaker fees/advisory board funds from Actelion, ATI, Biogen, ElectroCore, Sanofi-Genzyme, Novartis, Mitsubishi Pharma Europe, and TEVA; research grants from EFIC-Grünenthal, Novartis Switzerland, the Swiss Multiple Sclerosis Society, and the Swiss National Science Foundation.
R. Robinson: employee of and holds stock/stock options in AbbVie Inc.
J. Smith, G. Lima, B. Parks B, G. Giannattasio, S. Eraly: employees of and hold stock/stock options in Biogen.
Supported by: Biogen and AbbVie Inc. Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen and AbbVie Inc.
Abstract: EP1704
Type: ePoster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: SELECTED (NCT01051349) was an open-label extension study that evaluated treatment with daclizumab beta (DAC BETA) for up to 6 additional years in patients with relapsing MS (RMS) who completed the randomized SELECT/SELECTION studies. A previous interim analysis of SELECTED showed that efficacy was maintained over 3 years of continuous treatment and adverse events (AEs) did not increase over time.
Objective: To report the long-term safety and efficacy outcomes in RMS patients treated with DAC BETA in SELECTED.
Methods: Patients who completed 1-2 years of treatment with DAC BETA in SELECT/SELECTION were eligible to receive open-label DAC BETA 150mg subcutaneous every 4 weeks for up to 6 more years in SELECTED. To consolidate extension studies, SELECTED was stopped early and patients transitioned to the open-label EXTEND (NCT01797965) study that also includes patients from DECIDE and OBSERVE.
Results: 90% (410/455) of patients who completed treatment in SELECT/SELECTION enrolled in SELECTED. The mean (median) time on treatment in SELECTED was 40.2 (45.1; range:0-66) months; 69% of patients received DAC BETA for >3 years, 39% for >4 years and 9% for >5 years. The incidence of AEs in Years 1, 2, 3, 4 and ≥5 was 60%, 60%, 57%, 56% and 51%. 87% of patients experienced an AE; 26%, a serious AE excluding MS relapse. Most patients (75%) had AEs that were mild/moderate in severity. There were no deaths during the study. Incidence of alanine transaminase and/or aspartate transaminase elevations >5x upper limit of normal was 9% and 6%, respectively.The adjusted annualised relapse rate (95%CI) in Years 1, 2, 3, 4 and ≥5 was 0.150 (0.111, 0.205), 0.122 (0.087, 0.170), 0.105 (0.074, 0.148), 0.133 (0.084, 0.211) and 0.087 (0.054, 0.140). The incidence of 24-week confirmed disability progression was low (17.4%) with a stable rate of occurrence over the study period. The mean numbers of new Gd+ and new/newly enlarging T2 hyperintense lesions occurred at rates similar to the reduced rates in SELECT/SELECTION. The percentage change in whole brain volume was −0.4%, −0.4%, −0.2%, −0.5%, −0.2% and 0.1% for Years 1, 2, 3, 4, 5 and 6, respectively.
Conclusions: Results from SELECTED extend those from SELECT/SELECTION and together show that the effects of DAC BETA on clinical and radiologic outcomes and the favourable benefit/risk profile of DAC BETA were sustained over up to ~8 years of treatment, with no new safety concerns identified in the SELECTED study population.
Disclosure:
R. Gold: consulting fees from Bayer HealthCare, Biogen, Novartis, Merck Serono, Sanofi-Aventis, and Teva; editor of Therapeutic Advances in Neurological Disorders; research support from Biogen, Genzyme, Merck Serono, Novartis, and Teva.
E.-W. Radue: speaker fees from Actelion, Basilea, Bayer HealthCare, Biogen, Merck Serono, and Novartis; research support from Actelion, Bayer HealthCare, Biogen, Merck Serono, and Novartis.
G. Giovannoni: advisory boards for AbbVie Inc., Almirall, Atara Bio, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi-Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis and Teva; co-editor in chief of Multiple Sclerosis and Related Disorders; research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono and Novartis.
K. Selmaj: consulting fees from Genzyme, Novartis, Ono, Roche, Synthon, and Teva; speaker fees from Biogen.
E. Havrdova: honoraria/research support from Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche and Teva; advisory boards for Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis and Roche; supported by the Czech Ministry of Education research project PROGRES Q27/LF1.
X. Montalban: speaker fees/travel expense reimbursement from and steering committee/advisory boards for Actelion, Almirall, Bayer HealthCare, Biogen, Genzyme, Merck, Neurotec, Novartis, Octapharma, Receptos, Roche, Sanofi-Aventis, Teva, and Trophos.
D. Stefoski: consulting fees from Acorda, Biogen, Serono, and Teva Neuroscience; speaker fees from Acorda, Biogen, Elan, EMD Serono, and Teva Neuroscience; royalty payments of licensed drug from Acorda; research support from Biogen, Novartis, Pfizer, and Serono.
T. Sprenger: the University Hospital Basel (previous employer) and/or current (DKD Helios Klinik Wiesbaden) employer of TS received speaker fees/advisory board funds from Actelion, ATI, Biogen, ElectroCore, Sanofi-Genzyme, Novartis, Mitsubishi Pharma Europe, and TEVA; research grants from EFIC-Grünenthal, Novartis Switzerland, the Swiss Multiple Sclerosis Society, and the Swiss National Science Foundation.
R. Robinson: employee of and holds stock/stock options in AbbVie Inc.
J. Smith, G. Lima, B. Parks B, G. Giannattasio, S. Eraly: employees of and hold stock/stock options in Biogen.
Supported by: Biogen and AbbVie Inc. Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen and AbbVie Inc.