(MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.
Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.
The phase 3 DECIDE study () compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).
To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics,PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.
Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.
Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups werein terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.
Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.
The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.
In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.
“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.
Biogen and AbbVie Biotherapeutics supported the study.
SOURCE: Cohan S et al. Mult Scler J. 2018.
This article was updated on 3/22/19.