Contributions
Abstract: P606
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: There is growing acceptance that a neurophysical disability progression composite endpoint (NDPC) may provide a more objective, reliable and sensitive way to monitor disability progression (Mult Scler 2015; 21(11Sup):P638). DECIDE compared daclizumab high-yield process
(DAC HYP, 150mg subcutaneous, every 4 weeks, N=919) and interferon beta-1a (IM IFN beta-1a, 30mcg intramuscular, once weekly, N=922). Here, individual domain contributions to the NDPC, and effects of DAC HYP on the NDPC were assessed.
Method: Domain contributions to the NDPC were assessed in a pooled treatment group analysis of a 24-week confirmed disability progression (CDP) events with no relapse within the 74 days prior to onset. CDP on the NDPC was achieved by meeting one or more of: 20% increase from baseline (BL) in 9 Hole Peg Test (9HPT) or in Timed 25 Foot Walk (T25FW), or ≥ 1.0 point increase in Expanded Disability Status Scale (EDSS). Efficacy of DAC HYP on the NDPC was compared post hoc to IM IFN beta-1a using a cox regression model in a cohort of patients (pts) with BL EDSS score ≥3.5, a population at-risk for CDP.
Result: Of 264/1841 pts with the first instance of CDP on the NDPC, 90 (34.1%) were captured solely by EDSS, 29 (11.0%) by 9HPT, 128 (48.5%) by T25FW, and 17 (6.4%) by multiple domains. BL EDSS scores varied within groups of pts who had CDP captured by each individual domain, with no specific range captured by a specific domain (e.g. 8.9% of pts with BL EDSS score of 2.0 [n=348] had T25FW CDP, 5.8% of BL EDSS 2.5 [n=173], 6.9% of 3.0 [n=188], 6.6% of 3.5 [n=213], 10.2% of 4.0 [n=157], 6.7% of 4.5 [n=90], and 11.5% of 5.0 [n=87]). In pts with BL EDSS ≥3.5, DAC HYP (n=260) was more effective than IM IFN beta-1a (n=291) in slowing the accumulation of disability exclusive of acute relapse, based on the NDPC, hazard ratio [95% CI]: 0.65 [0.44, 0.98], nominal p=0.04. Full safety data from DECIDE were previously described (N Engl J Med 2015; 373:1418-28).
Conclusion: The individual domains of the NDPC appear to selectively capture pts´ first instance of CDP of upper extremity dexterity, lower extremity ambulatory or broader spectrum disability progression, with little overlap. The basis for this variable sensitivity did not appear to be related to BL disability (EDSS). Treatment with DAC HYP was more effective than IM IFN beta-1a in slowing disability progression in relapsing-remitting MS pts with moderate/severe BL disability, independent of acute relapse.
Disclosure: Biogen and AbbVie Biotherapeutics Inc. participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication.
J.L. Bennett is on the editorial board for Journal of Neuro-ophthalmology, Multiple Sclerosis, and Neurology: Neuroimmunology & Neuroinflammation; holds patents for compositions and methods for the treatment of neuromyeltis optica, novel blocking monoclonal therapy for neuromyelitis optica; consulted for EMD-Serono, Questcor Pharmaceuticals, Alnaylam Pharmaceuticals, Medimmune, Abbvie, Novartis Pharmaceuticals, Chugai Pharmaceuticals, Genzyme, Genentech; received research support from Questcor Pharmaceuticals, Novartis Pharmaceuticals, NIH, Guthy-Jackson Foundation; holds stock in Apsara Therapeutics; and receives license fees and royalty payments from Aquaporumab. B.A.C. Cree has received compensation for consulting from Abbvie, Biogen, EMD Serono, MedImmune, Novartis, Sanofi Genzyme, Shire and Teva. T. Leist has received compensation for consulting from Abbvie, EMDSerono, Novartis, Genentech, Teva, Biogen, Bayer, Genzyme and for speaking from Novartis, Teva, Biogen,Genzyme. H. Moses has received compensation for consulting and speaking from Biogen, Bayer, Teva, EMDSerono, AbbVie, Genzyme and Novartis. G. Giovannoni received fees for participation in advisory board for AbbVie Biotherapeutics Inc., Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi-Genzyme, Synthon, Teva, and Vertex; speaker fees from AbbVie Biotherapeutics Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis, and Teva; coeditor in chief of Multiple Sclerosis and Related Disorders; research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono, and Novartis.
J. Zhao, M. Li, L. Chiodo, R.R. Robinson and S.J. Greenberg are full-time employees of AbbVie Biotherapeutics and may hold stock or options.
Abstract: P606
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: There is growing acceptance that a neurophysical disability progression composite endpoint (NDPC) may provide a more objective, reliable and sensitive way to monitor disability progression (Mult Scler 2015; 21(11Sup):P638). DECIDE compared daclizumab high-yield process
(DAC HYP, 150mg subcutaneous, every 4 weeks, N=919) and interferon beta-1a (IM IFN beta-1a, 30mcg intramuscular, once weekly, N=922). Here, individual domain contributions to the NDPC, and effects of DAC HYP on the NDPC were assessed.
Method: Domain contributions to the NDPC were assessed in a pooled treatment group analysis of a 24-week confirmed disability progression (CDP) events with no relapse within the 74 days prior to onset. CDP on the NDPC was achieved by meeting one or more of: 20% increase from baseline (BL) in 9 Hole Peg Test (9HPT) or in Timed 25 Foot Walk (T25FW), or ≥ 1.0 point increase in Expanded Disability Status Scale (EDSS). Efficacy of DAC HYP on the NDPC was compared post hoc to IM IFN beta-1a using a cox regression model in a cohort of patients (pts) with BL EDSS score ≥3.5, a population at-risk for CDP.
Result: Of 264/1841 pts with the first instance of CDP on the NDPC, 90 (34.1%) were captured solely by EDSS, 29 (11.0%) by 9HPT, 128 (48.5%) by T25FW, and 17 (6.4%) by multiple domains. BL EDSS scores varied within groups of pts who had CDP captured by each individual domain, with no specific range captured by a specific domain (e.g. 8.9% of pts with BL EDSS score of 2.0 [n=348] had T25FW CDP, 5.8% of BL EDSS 2.5 [n=173], 6.9% of 3.0 [n=188], 6.6% of 3.5 [n=213], 10.2% of 4.0 [n=157], 6.7% of 4.5 [n=90], and 11.5% of 5.0 [n=87]). In pts with BL EDSS ≥3.5, DAC HYP (n=260) was more effective than IM IFN beta-1a (n=291) in slowing the accumulation of disability exclusive of acute relapse, based on the NDPC, hazard ratio [95% CI]: 0.65 [0.44, 0.98], nominal p=0.04. Full safety data from DECIDE were previously described (N Engl J Med 2015; 373:1418-28).
Conclusion: The individual domains of the NDPC appear to selectively capture pts´ first instance of CDP of upper extremity dexterity, lower extremity ambulatory or broader spectrum disability progression, with little overlap. The basis for this variable sensitivity did not appear to be related to BL disability (EDSS). Treatment with DAC HYP was more effective than IM IFN beta-1a in slowing disability progression in relapsing-remitting MS pts with moderate/severe BL disability, independent of acute relapse.
Disclosure: Biogen and AbbVie Biotherapeutics Inc. participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication.
J.L. Bennett is on the editorial board for Journal of Neuro-ophthalmology, Multiple Sclerosis, and Neurology: Neuroimmunology & Neuroinflammation; holds patents for compositions and methods for the treatment of neuromyeltis optica, novel blocking monoclonal therapy for neuromyelitis optica; consulted for EMD-Serono, Questcor Pharmaceuticals, Alnaylam Pharmaceuticals, Medimmune, Abbvie, Novartis Pharmaceuticals, Chugai Pharmaceuticals, Genzyme, Genentech; received research support from Questcor Pharmaceuticals, Novartis Pharmaceuticals, NIH, Guthy-Jackson Foundation; holds stock in Apsara Therapeutics; and receives license fees and royalty payments from Aquaporumab. B.A.C. Cree has received compensation for consulting from Abbvie, Biogen, EMD Serono, MedImmune, Novartis, Sanofi Genzyme, Shire and Teva. T. Leist has received compensation for consulting from Abbvie, EMDSerono, Novartis, Genentech, Teva, Biogen, Bayer, Genzyme and for speaking from Novartis, Teva, Biogen,Genzyme. H. Moses has received compensation for consulting and speaking from Biogen, Bayer, Teva, EMDSerono, AbbVie, Genzyme and Novartis. G. Giovannoni received fees for participation in advisory board for AbbVie Biotherapeutics Inc., Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi-Genzyme, Synthon, Teva, and Vertex; speaker fees from AbbVie Biotherapeutics Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis, and Teva; coeditor in chief of Multiple Sclerosis and Related Disorders; research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono, and Novartis.
J. Zhao, M. Li, L. Chiodo, R.R. Robinson and S.J. Greenberg are full-time employees of AbbVie Biotherapeutics and may hold stock or options.