# Abstract

 

## Background: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain. 

## Objective: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT). 

## Methods: In DECIDE, patients with relapsing--remitting multiple sclerosis (RRMS) (age: 18--55 years; Expanded Disability Status Scale (EDSS) score 0--5.0) were randomized to daclizumab beta ( *n* = 919) or IM IFN beta-1a ( *n* = 922) for 96--144 weeks. SDMT was administered at baseline and at 24-week intervals. 

## Results: At week 96, significantly greater mean improvement from baseline in SDMT was observed with daclizumab beta versus IM IFN beta-1a ( *p* = 0.0274). Significantly more patients treated with daclizumab beta showed clinically meaningful improvement in SDMT (increase from baseline of ⩾3 points ( *p* = 0.0153) or ⩾4 points ( *p* = 0.0366)), and significantly fewer patients showed clinically meaningful worsening (decrease from baseline of ⩾3 points ( *p* = 0.0103)). Odds representing risk of worsening versus stability or improvement on SDMT were significantly smaller for daclizumab beta ( *p* = 0.0088 (3-point threshold); *p* = 0.0267 (4-point threshold)). In patients completing 144 weeks of treatment, the effects of daclizumab beta were generally sustained. 

## Conclusion: These results provide evidence for a benefit of daclizumab beta versus IM IFN beta-1a on cognitive processing speed in RRMS. 

## Trial registration: ClinicalTrials.gov identifier NCT01064401 (Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis (DECIDE)): [https://clinicaltrials.gov/ct2/show/NCT01064401](#) . # Results 

## Descriptive data A total of 1841 patients were randomized (daclizumab beta, *n* = 919; IM IFN beta-1a, *n* = 922). All were included in the ITT population. Demographic and baseline MS disease characteristics were well balanced across treatment groups, as reported previously. ^[18](#)^At baseline, in the daclizumab beta and IM IFN beta-1a groups, mean (SD) SDMT score was 48.5 (15.9) and 47.7 (16.1), respectively, and median (range) SDMT score was 49 (0--110) and 49 (3--110), respectively. 

## Group effects on SDMT Based on the linear mixed model analysis approach, there was a significant group × time interaction ( *p* = 0.0004). Significantly greater mean improvement from baseline in SDMT scores was observed with daclizumab beta compared with IM IFN beta-1a at week 96 (mean (SD) change from baseline: 4.1 (12.4) vs 2.9 (12.7); *p* = 0.0274), as reported previously ( [Figure 1](#) ). ^[18](#)^This effect was sustained at week 144 (6.3 (12.6) vs 3.1 (13.2); *p* = 0.0024) in a limited number of patients completing 144 weeks of treatment with available SDMT scores (daclizumab beta, *n* = 287; IM IFN beta-1a, *n* = 277). <figure> <p><img src="" /></p> <figcaption>Mean change from baseline in Symbol Digit Modalities Test (SDMT) score at weeks 24, 48, 72, 96, and 144. Patients with available data for baseline covariates were included. Analyses were based on observed data with no imputation for missing data. IFN: interferon; IM: intramuscular; SD: standard deviation.</figcaption> </figure> 

## Clinically meaningful change and responder analyses In the GEE analysis, significantly more patients treated with daclizumab beta compared with IM IFN beta-1a showed clinically meaningful improvement, defined as a ⩾3-point increase on the SDMT, at week 96 (60.0% vs 54.1%; odds ratio (OR; 95% confidence interval, CI): 1.30 (1.05--1.62); *p* = 0.0153) and week 144 (65.5% vs 52.0%; OR (95% CI): 1.60 (1.18--2.19); *p* = 0.0028; [Figure 2(a)](#) ). Similarly, significantly more patients treated with daclizumab beta showed a ⩾4-point increase at week 96 (55.4% vs 50.1%; OR (95% CI): 1.26 (1.01--1.56); *p* = 0.0366) and week 144 (61.7% vs 48.4%; OR (95% CI): 1.53 (1.12--2.07); *p* = 0.0067; [Figure 2(b)](#) ). <figure> <p><img src="" /></p> <figcaption>Percentage of patients with (a) ⩾3-point improvement or (b) ⩾4-point improvement in Symbol Digit Modalities Test score at weeks 24, 48, 72, 96, and 144. Patients with available data for baseline covariates were included. Analyses were based on observed data with no imputation for missing data. IFN: interferon; IM: intramuscular.</figcaption> </figure> Significantly fewer patients treated with daclizumab beta versus IM IFN beta-1a showed clinically meaningful worsening, defined as a ⩾3-point decrease on the SDMT at week 96 (19.4% vs 24.8%; OR (95% CI): 0.72 (0.56--0.92); *p* = 0.0103; [Figure 3(a)](#) ). There was a trend for significance at week 144 (18.8% vs 26.4%; OR (95% CI): 0.72 (0.50--1.03); *p* = 0.0754). When clinically meaningful worsening was defined as a ⩾4-point decrease, there was a trend for significance at week 96 (17.5% vs 21.1%; OR: 0.78 (95% CI: 0.60--1.02); *p* = 0.0645) and no significant difference between daclizumab beta and IM IFN beta-1a at week 144 (17.1% vs 23.5%; OR: 0.77 (95% CI: 0.53--1.12); *p* = 0.1719; [Figure 3(b)](#) ). <figure> <p><img src="" /></p> <figcaption>Percentage of patients with (a) ⩾3-point decline or (b) ⩾4-point decline in Symbol Digit Modalities Test score at weeks 24, 48, 72, 96, and 144. Patients with available data for baseline covariates were included. Analyses were based on observed data with no imputation for missing data. IFN: interferon; IM: intramuscular.</figcaption> </figure> Based on the 3-point threshold, the percentage of patients exhibiting worsening, stability, and improvement at week 96 was 19.4%, 20.6%, and 60.0%, respectively, in the daclizumab beta group and 24.8%, 21.1%, and 54.1%, respectively, in the IM IFN beta-1a group ( [Figure 4(a)](#) ). Based on the 4-point threshold, the percentage of patients exhibiting worsening, stability, and improvement at week 96 was 17.5%, 27.1%, and 55.4%, respectively, in the daclizumab beta group and 21.1%, 28.7%, and 50.1%, respectively, in the IM IFN beta-1a group ( [Figure 4(b)](#) ). The OR (95% CI) for worsening and worsening or stable SDMT scores for daclizumab beta compared with IM IFN beta-1a was 0.75 (0.61--0.93; *p* = 0.0088) for the 3-point threshold and 0.79 (0.64--0.97; *p* = 0.0267) for the 4-point threshold. <figure> <p><img src="" /></p> <figcaption>Percentage of patients with worsened, stable, or improved Symbol Digit Modalities Test score at week 96 using (a) a 3-point threshold or (b) a 4-point threshold. Patients with available data for baseline covariates were included. Analyses were based on observed data with no imputation for missing data. CI: confidence interval; IFN: interferon; IM: intramuscular; OR: odds ratio.</figcaption> </figure>


Extracted trial result:
Outcome: clinically meaningful improvement at week 96 (⩾3-point increase on the SDMT) (binary)
Intervention: daclizumab beta
Comparator: intramuscular (IM) interferon (IFN) beta-1a
Intervention events: 432
Intervention group size: 720
Comparator events: 369
Comparator group size: 682
Notes: counts calculated from percentages given in text, totals found in figure