Contributions
Abstract: P618
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Daclizumab high-yield process (DAC HYP) showed significantly greater efficacy over intramuscular (IM) interferon (IFN) beta-1a on key clinical and radiologic outcomes in relapsing-remitting multiple sclerosis in DECIDE. Patients previously treated with IFN beta could enrol in DECIDE if they did not have any contraindication, known intolerance, or history of noncompliance with IM IFN beta-1a at randomisation.
Objectives: Evaluate the efficacy of DAC HYP versus IM IFN beta-1a in patients previously treated with IFN beta who did not have IFN beta neutralising antibodies (NAbs) at Baseline in DECIDE.
Methods: At Baseline, 308 (34%) DAC HYP patients (n=919) and 311 (34%) IM IFN beta-1a patients (n=922) had previously been treated with IFN beta. The protocol did not require testing for IFN beta NAbs at Baseline, except where required by local IFN beta prescribing guidelines. Baseline serum samples from patients previously treated with IFN beta were collected prospectively and tested post hoc for IFN beta NAbs. Efficacy analyses were performed post hoc using statistical models prespecified in the overall population: annualized relapse rate (ARR) and T2 lesions (negative binomial regression), 12- and 24-wk confirmed disability progression (CDP; [Cox proportional hazards]; 24-wk CDP: multiple imputation used to impute CDP in patients with no assessment to confirm CDP), gadolinium-enhancing (Gd+) lesions (ordinal logistic regression), and each adjusted for relevant Baseline factors.
Results: In the DAC HYP and IM IFN beta-1a groups, 12% (36/308) and 10% (32/311) of patients previously treated with IFN beta were determined to be IFN NAb positive at Baseline, respectively. After patients previously treated with IFN beta who were NAb positive at Baseline were excluded from the analysis population, efficacy analyses on the remaining patient data (DAC HYP, n=272; IM IFN beta-1a, n=279) were performed. For DAC HYP versus IM IFN beta-1a, ARR was reduced by 32% (95% CI: 13%-48%; P=.0027), risk of 12-week CDP by 31% (95% CI: −3%-53%; P=.0667), risk of 24-week CDP by 40% (95% CI: 3%-63%; P=.0371), the odds of having more Gd+ lesions by 72% (95% CI: 57%-82%; P< .0001), and the number of new/newly enlarging T2 hyperintense lesions by 45% (95% CI: 26%-58%; P< .0001).
Conclusions: As was observed with the overall population in DECIDE, DAC HYP provided benefits over IM IFN beta-1a in patients previously treated with IFN beta who were not NAb positive at Baseline.
Disclosure:
Antonio Bertolotto: received honoraria for serving on the scientific advisory boards of Admirall, Biogen, Merck, and received speaker honoraria from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, and Teva; his institution has received research support from Admirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, and the Italian Multiple Sclerosis Society, Associazione Ricerca Biomedica and San Luigi Onlus;
Per Soelberg Sørensen: received personal compensation for serving on scientific advisory boards, steering committees or independent data monitoring boards: Biogen, Forward Pharma, Genzyme, GlaxoSmithKline, medDay Pharmaceuticals, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd.; speaker honoraria: Biogen, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd. Danish Multiple Sclerosis Center, Department of Neurology has received research support from Bayer, Biogen, Merck Serono, Novartis, Roche, RoFAR, Sanofi-Aventis/Genzyme, Teva Pharmaceutical Industries Ltd, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Programmes;
Mads Ravnborg: received travel grants and advisory honoraria from Bayer Health, Biogen, Genzyme, Merck Serono, Novartis, and Sanofi Aventis;
Stanley Cohan: paid consultant to serve on advisory boards for Biogen, Mallinckrodt, Novartis, and Sanofi-Genzyme; honoraria from speaker bureaus for Acorda, Biogen, Genentech, Novartis, and Sanofi-Genzyme; research support from Biogen, Genentech, Mallinckrodt, Novartis, Opexa, Roche, and Sanofi-Genzyme; funds for transportation, meals, and lodging from Acorda, Biogen, Mallinckrodt, Novartis, and Sanofi-Genzyme;
Ping Wang and Sami Fam: employees of and hold stock/stock options in Biogen.
Supported by: Biogen and AbbVie Biotherapeutics Inc.
Biogen and AbbVie Biotherapeutics Inc. provided funding for medical writing support in the development of this abstract. Alison Gagnon (Excel Scientific Solutions, Southport, CT) wrote the first draft of the abstract based on input from authors. Biogen and AbbVie Biotherapeutics Inc. reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract, and provided their final approval of all content.
Abstract: P618
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Daclizumab high-yield process (DAC HYP) showed significantly greater efficacy over intramuscular (IM) interferon (IFN) beta-1a on key clinical and radiologic outcomes in relapsing-remitting multiple sclerosis in DECIDE. Patients previously treated with IFN beta could enrol in DECIDE if they did not have any contraindication, known intolerance, or history of noncompliance with IM IFN beta-1a at randomisation.
Objectives: Evaluate the efficacy of DAC HYP versus IM IFN beta-1a in patients previously treated with IFN beta who did not have IFN beta neutralising antibodies (NAbs) at Baseline in DECIDE.
Methods: At Baseline, 308 (34%) DAC HYP patients (n=919) and 311 (34%) IM IFN beta-1a patients (n=922) had previously been treated with IFN beta. The protocol did not require testing for IFN beta NAbs at Baseline, except where required by local IFN beta prescribing guidelines. Baseline serum samples from patients previously treated with IFN beta were collected prospectively and tested post hoc for IFN beta NAbs. Efficacy analyses were performed post hoc using statistical models prespecified in the overall population: annualized relapse rate (ARR) and T2 lesions (negative binomial regression), 12- and 24-wk confirmed disability progression (CDP; [Cox proportional hazards]; 24-wk CDP: multiple imputation used to impute CDP in patients with no assessment to confirm CDP), gadolinium-enhancing (Gd+) lesions (ordinal logistic regression), and each adjusted for relevant Baseline factors.
Results: In the DAC HYP and IM IFN beta-1a groups, 12% (36/308) and 10% (32/311) of patients previously treated with IFN beta were determined to be IFN NAb positive at Baseline, respectively. After patients previously treated with IFN beta who were NAb positive at Baseline were excluded from the analysis population, efficacy analyses on the remaining patient data (DAC HYP, n=272; IM IFN beta-1a, n=279) were performed. For DAC HYP versus IM IFN beta-1a, ARR was reduced by 32% (95% CI: 13%-48%; P=.0027), risk of 12-week CDP by 31% (95% CI: −3%-53%; P=.0667), risk of 24-week CDP by 40% (95% CI: 3%-63%; P=.0371), the odds of having more Gd+ lesions by 72% (95% CI: 57%-82%; P< .0001), and the number of new/newly enlarging T2 hyperintense lesions by 45% (95% CI: 26%-58%; P< .0001).
Conclusions: As was observed with the overall population in DECIDE, DAC HYP provided benefits over IM IFN beta-1a in patients previously treated with IFN beta who were not NAb positive at Baseline.
Disclosure:
Antonio Bertolotto: received honoraria for serving on the scientific advisory boards of Admirall, Biogen, Merck, and received speaker honoraria from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, and Teva; his institution has received research support from Admirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, and the Italian Multiple Sclerosis Society, Associazione Ricerca Biomedica and San Luigi Onlus;
Per Soelberg Sørensen: received personal compensation for serving on scientific advisory boards, steering committees or independent data monitoring boards: Biogen, Forward Pharma, Genzyme, GlaxoSmithKline, medDay Pharmaceuticals, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd.; speaker honoraria: Biogen, Genzyme, Merck Serono, Novartis, and Teva Pharmaceutical Industries Ltd. Danish Multiple Sclerosis Center, Department of Neurology has received research support from Bayer, Biogen, Merck Serono, Novartis, Roche, RoFAR, Sanofi-Aventis/Genzyme, Teva Pharmaceutical Industries Ltd, the Danish Multiple Sclerosis Society, the Danish Medical Research Council, and the European Union Programmes;
Mads Ravnborg: received travel grants and advisory honoraria from Bayer Health, Biogen, Genzyme, Merck Serono, Novartis, and Sanofi Aventis;
Stanley Cohan: paid consultant to serve on advisory boards for Biogen, Mallinckrodt, Novartis, and Sanofi-Genzyme; honoraria from speaker bureaus for Acorda, Biogen, Genentech, Novartis, and Sanofi-Genzyme; research support from Biogen, Genentech, Mallinckrodt, Novartis, Opexa, Roche, and Sanofi-Genzyme; funds for transportation, meals, and lodging from Acorda, Biogen, Mallinckrodt, Novartis, and Sanofi-Genzyme;
Ping Wang and Sami Fam: employees of and hold stock/stock options in Biogen.
Supported by: Biogen and AbbVie Biotherapeutics Inc.
Biogen and AbbVie Biotherapeutics Inc. provided funding for medical writing support in the development of this abstract. Alison Gagnon (Excel Scientific Solutions, Southport, CT) wrote the first draft of the abstract based on input from authors. Biogen and AbbVie Biotherapeutics Inc. reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract, and provided their final approval of all content.