Consistent efficacy of daclizumab beta across patient demographic and disease activity subgroups in patients with relapsing-remitting multiple sclerosis

Highlights

• Efficacy of daclizumab beta on ARR was assessed in patient subgroups.

• Daclizumab beta resulted in lower ARRs than placebo across nearly all subgroups.

• Daclizumab beta caused lower ARRs than interferon beta-1a across all subgroups.

• ARR reductions were supported by reductions in MRI lesion activity.

Abstract

Background

Daclizumab beta is a humanized monoclonal antibody specific for the human interleukin-2 receptor alpha chain (CD25). In two pivotal studies in relapsing multiple sclerosis (MS), patients treated with daclizumab beta exhibited lower annualized relapse rates (ARR) when compared with placebo or with intramuscular (IM) interferon beta-1a.

Objectives

To determine if the efficacy of daclizumab beta demonstrated in the phase 2 SELECT study and the phase 3 DECIDE study was consistent in patient subgroups.

Methods

In the SELECT study, patients received daclizumab beta 150 or 300 mg administered subcutaneously every 4 weeks for 52 weeks, and were compared with patients who received placebo. In the DECIDE study, patients received daclizumab beta 150 mg administered subcutaneously every 4 weeks for 96–144 weeks, and were compared with patients who received IM interferon beta-1a 30 µg. Subgroups were defined by sex, age, the number of relapses in the year before the study, disease duration, baseline disability measured by EDSS, presence of Gd-enhancing lesions, T2 hyperintense lesion volume at baseline, and previous interferon beta-1a use.

Results

Treatment with daclizumab beta was associated with relative lower ARR, with 95% confidence intervals (CIs) below 1 in 13 of 15 subgroups (SELECT study) compared with placebo and in all 17 subgroups compared with interferon beta-1a (DECIDE study). In 2 subgroups in the SELECT study (patients who were older than 35 years of age or who had a disease duration of 10 or more years), the rate ratio point estimate for the ARR was in favor of daclizumab beta but the 95% CI overlapped with 1. The clinical benefits in ARR achieved with daclizumab beta treatment compared with placebo or interferon beta-1a across subgroups were similarly supported by reductions in lesion activity on magnetic resonance images (MRIs).

Conclusions

These findings suggest that treatment with daclizumab beta is consistently effective among clinically important patient subgroups and support its potential as a viable therapeutic option across the spectrum of relapsing MS.

Introduction

Daclizumab beta,¹ a humanized monoclonal antibody, binds to the alpha subunit (CD25) of the high-affinity interleukin-2 receptor (IL-2R) (Martin, 2012, Wiendl and Gross, 2013), preventing signaling via the high-affinity IL-2R and thereby increasing the availability of interleukin-2 to signal at the intermediate affinity receptor (Bielekova, 2013, Wiendl and Gross, 2013). Daclizumab beta is thought to provide therapeutic effects in multiple sclerosis (MS) by reversibly modulating interleukin-2 signaling, resulting in targeted antagonism of proinflammatory activated T cell responses and expansion of immunoregulatory CD56^bright natural killer cells. (Elkins et al., 2015, Gold et al., 2013, Wiendl and Gross, 2013). In the SELECT study, patients with relapsing MS treated with daclizumab beta for 52 weeks had significantly lower annualized relapse rates (ARRs) when compared with placebo (Gold et al., 2013). In the 2–3-year DECIDE study, relapsing MS patients treated with daclizumab beta had significantly lower ARRs than did patients treated with intramuscular (IM) interferon beta-1a after at least 96 weeks (up to 144 weeks for patients who completed a third year) of treatment (Kappos et al., 2015). In both studies, treatment with daclizumab beta resulted in significant reductions in all brain magnetic resonance imaging (MRI) parameters evaluated, including T1 Gd-enhancing and new/newly enlarging T2 lesion activity (Gold et al., 2013, Kappos et al., 2015).

Even if clinical studies demonstrate overall efficacy and safety, the effects may not be consistent across different patient demographics and baseline disease characteristics. For example, treatments for the indication of relapsing forms of MS may vary in efficacy between genders and across different age groups (Lucchinetti et al., 2000). Treatment response can also vary across different clinical and MRI baseline disease characteristics that are known predictors of a more aggressive clinical course (Held et al., 2005, Kantarci and Weinshenker, 2001, Miller et al., 2005, Miller, 2004). Therefore, we performed a series of analyses to determine if the efficacy of daclizumab beta in patient subgroups based on demographics and baseline disease characteristics was consistent with the overall patient populations in a placebo-controlled (SELECT) and an active comparator-controlled (DECIDE) clinical study (Gold et al., 2013, Kappos et al., 2015).