Efficacy of daclizumab beta versus intramuscular interferon beta-1a on disability progression across patient demographic and disease activity subgroups in DECIDE

Stanley Cohan, Ludwig Kappos, Gavin Giovannoni, Heinz Wiendl, Krzysztof Selmaj, Eva Kubala Havrdová, John Rose, Steven Greenberg, Glenn Phillips, Wei Ma, Ping Wang, Gabriel Lima, Guido Sabatella, Stanley Cohan, Ludwig Kappos, Gavin Giovannoni, Heinz Wiendl, Krzysztof Selmaj, Eva Kubala Havrdová, John Rose, Steven Greenberg, Glenn Phillips, Wei Ma, Ping Wang, Gabriel Lima, Guido Sabatella

Abstract

Background: Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments.

Objective: Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE.

Methods: Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics.

Results: Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS progression (HR, 0.80; 95% CI, 0.67-0.95), and odds of clinically meaningful worsening in MSIS-29 PHYS (odds ratio, 0.76; 95% CI, 0.60-0.95) versus IM interferon beta-1a. Point estimates showed trends favoring daclizumab beta over IM interferon beta-1a across several patient subgroups for all three outcome measures.

Conclusion: Daclizumab beta showed consistent benefit versus IM interferon beta-1a across measures assessing patient disability/function and across a range of clinical baseline characteristics in patients with relapsing-remitting MS.

Trial registration: ClinicalTrials.gov NCT01064401.

Keywords: Daclizumab beta; disability progression; efficacy; interferon beta-1a; relapsing-remitting multiple sclerosis; subgroup analysis.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Cohan has received consulting fees from Biogen, Genzyme, Mallinckrodt, and Novartis; participated in speaker bureaus for Acorda, Biogen, Genentech, Genzyme, and Novartis; and received research support from Biogen, Genentech, Genzyme, Mallinckrodt, Novartis, Opexa, and Roche. Ludwig Kappos’ institution (University Hospital Basel) received steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport in the last 3 years, which were used exclusively for research support. Professor Kappos has received speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; license fees for Neurostatus products; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation. The respective payments were payed to University Hospital Basel and used exclusively for research support. Professor Giovannoni has served on advisory boards for AbbVie Biotherapeutics Inc., Biogen, Canbex, Ironwood, Merck, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Synthon, Teva and Vertex; received speaker fees from AbbVie Biotherapeutics Inc., Bayer HealthCare, Biogen, Genzyme, Merck Serono, Sanofi-Aventis, and Teva; is co-editor in chief of Multiple Sclerosis and Related Disorders; and has received research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono and Novartis. Dr Wiendl has received consulting fees/honoraria from Bayer HealthCare, Biogen, Fresenius Medical Care, GlaxoSmithKline, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Genzyme and Teva; received grants from and contracts with Bayer HealthCare, Biogen, Deutsche Forschungsgesellschaft, the Else Kröner-Fresenius Foundation, the German Ministry for Education and Research, the Hertie Foundation, the Interdisciplinary Center for Clinical Studies in Münster, Germany, Merck Serono, Novartis, the NRW Ministry of Education and Research, the RE Children’s Foundation, Sanofi-Genzyme and Teva. Professor Selmaj has received consulting fees from Genzyme, Novartis, Ono, Roche, Synthon and Teva; and speaker fees from Biogen. Dr Havrdová has received honoraria/research support from Actelion, Biogen, Merck Serono, Novartis, Celgene, Sanofi-Genzyme and Teva; and has served on advisory boards for Biogen, Celgene, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva. She has been supported by the Ministry of Education of Czech Republic, program PRVOUK-P26/LF1/4. Dr Rose has received research support from AbbVie Biotherapeutics Inc., Biogen, Cumming Foundation, the National Institutes of Health, the National Multiple Sclerosis Society, Teva and the U.S. Department of Veterans Affairs. Dr Greenberg was an employee of AbbVie at the time of this analysis and the writing of this manuscript; holds stock/stock options in AbbVie. Drs. Phillips, Lima and Sabatella are full-time employees of and hold stock/stock options in Biogen. Dr Wang and Dr Ma were employees of Biogen at the time of this analysis and the writing of this manuscript; both hold stock in Biogen. Dr Wang’s current affiliation is with Shire, Lexington, MA, USA. Dr Ma’s current affiliation is with Institute of Statistics and Big Data, Renmin University of China.

Figures

Figure 1.
Figure 1.
Forest plot for 24-week confirmed disability progression for daclizumab beta versus IM IFN beta-1a by baseline demographics and disease characteristics. CI: confidence interval; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing; IFN: interferon; IM: intramuscular; MS: multiple sclerosis; SC: subcutaneous. aMissing baseline Gd+ lesions data: IM IFN beta-1a,n = 13; daclizumab beta, n = 19. bMissing baseline T2 hyperintense lesion volume data: IM IFN beta-1a, n = 14; daclizumab beta, n = 19. cMissing baseline disease activity data: IM IFN beta-1a,n = 5; daclizumab beta, n = 12.
Figure 2.
Figure 2.
Forest plot for 24-week sustained modified Multiple Sclerosis Functional Composite progression for daclizumab beta versus IM IFN beta-1a by baseline demographics and disease characteristics. CI: confidence interval; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing; IFN: interferon; IM: intramuscular; MS: multiple sclerosis; SC: subcutaneous. aMissing baseline Gd+ lesions data: IM IFN beta-1a,n = 13; daclizumab beta, n = 19. bMissing baseline T2 hyperintense lesion volume data: IM IFN beta-1a, n = 14; daclizumab beta, n = 19. cMissing baseline disease activity data: IM IFN beta-1a,n = 5; daclizumab beta, n = 12.
Figure 3.
Figure 3.
Forest plot for proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale score at week 96 for daclizumab beta versus IM IFN beta-1a by baseline demographics and disease characteristics. aOnly patients with available baseline assessment were included in the overall MSIS-29 PHYS analysis. bPatients included in the overall MSIS-29 PHYS analysis with missing baseline Gd+ lesions data: IM IFN beta-1a,n = 12; daclizumab beta, n = 17. cPatients included in the overall MSIS-29 PHYS analysis with missing baseline T2 hyperintense lesion volume data: IM IFN beta-1a,n = 13; daclizumab beta, n = 17. dPatients included in the overall MSIS-29 PHYS analysis missing baseline disease activity data: IM IFN beta-1a,n = 4; daclizumab beta, n = 11.

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