Daclizumab vs. Interferon Compared in Moderately, Severely Disabled RRMS Patients
VANCOUVER, BC—Daclizumab high-yield process (DAC HYP) demonstrated greater efficacy than interferon (IFN) beta-1a in prolonging the onset of disability progression in relapsing-remitting multiple sclerosis (RRMS), according to a post-hoc analysis of the randomized, double-blind Phase 3 DECIDE clinical trial, reported in a poster presentation at the 68th AAN Annual Meeting.
“These analyses provide additional support for DAC HYP effectiveness in slowing disability progression, independent of relapses, in a moderately/severely disabled cohort,” reported lead study author Jeffrey Bennett, MD, of the University of Colorado Denver School of Medicine, in Aurora, CO, and coauthors.
Disability in MS can accumulate either because of acute inflammation and clinical relapse, or because of relapse-independent disease progression, the coauthors noted. Their study therefore included both types of disability progression (disability progression without acute relapses or progression regardless of relapse activity) in their analysis.
“A neurophysical composite endpoint is in use in clinical trials of MS to provide a more objective, sensitive, and clinically-relevant disability measure, that may overcome limitations of the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC),” they wrote.
The neurophysical composite's components included: (1) 20% increase from baseline in 9-Hole Peg Test (9HPT) mean score from two hands; (2) 20% increase over baseline in Timed 25-Foot Walk (T25FW); and (3) a ≥1.0 point increase in EDSS.
In order to compare DAC HYP's and IM IFN beta-1a's efficacy in slowing disability progression with the neurophysical composite endpoint and its component measures, the researchers conducted a post-hoc analysis of data from the DECIDE trial. Efficacy was compared for DAC HYP and IM IFN beta-1a with data from a cohort of moderately/severely disabled study participants with baseline EDSS of ≥3.5, at 12 and 24 weeks. (This patient cohort was described by the coauthors as a “representative sample of RRMS patients who are at risk of disability progression.”)
Separate analyses were also conducted for 24-week confirmed disability progression for patients with no on-study relapse activity.
9HPT and particularly T25FW each more sensitively detected treatment effects than EDSS alone, they reported.
“DAC HYP showed a trend for reducing the risk of disability progression at 24 weeks compared with IM IFN beta-1a in moderately/severely disabled patients who did not relapse during the study,” the researchers reported. “Applying the neurophysical composite endpoints in this cohort, progression was most often identified by an increase in either T25FW or EDSS, with few cases of progression in multiple criteria.”
For patients with no on-study relapses, the 24-week neurophysical composite hazard ratio (HR) for DAC HYP vs. IM IFN beta-1a was 0.55 (95% CI: 0.29, 1.08; P=0.08); the component HRs were 0.35 for T25FW (95% CI: 0.14, 0.84; P=0.0188) and 0.43 for 9HPT (95% CI: 0.11,1.67; P=0.22, not significant). The EDSS HR was 1.03 (P=0.95, n.s.).
“DAC HYP also demonstrated a favorable trend for reducing disability progression compared with IM IFN beta-1a independent of acute relapses, with the neurophysical composite endpoint identifying a statistically significant difference between treatments” (HR 0.66; 95% CI: 0.44,0.98; P=0.0395), the coauthors reported.
“DAC HYP demonstrated an acceptable safety profile in this cohort of moderately/severely disabled RRMS patients,” they reported. Adverse events and most common AEs were similar between treatment groups but a “slight increase” in serious AEs (SAEs), but not treatment discontinuations, was noted in the DAC HYP study group (any SAE: 34% vs. 29%; discontinuations due to AEs: 10% vs. 10%).
The study was funded by AbbVie Biotherapeutics (Redwood City, CA) and Biogen (Cambrdige, MA); the firms participated in study design, data collection, analysis, and interpretation.