• Demyelinating Diseases
• Neurology Clinical Trials

• Demyelinating Diseases
• Neurology Clinical Trials
• Neurology

Ludwig Kappos, MD, University Hospital, Basel, Switzerland, described the results of the phase 3, randomized, double-blind, double-dummy, active-controlled Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis trial [DECIDE; NCT01064401] establishing the superiority of the humanized monoclonal antibody, daclizumab high-yield process (DAC HYP), to interferon beta-1a (IFN-β-1a) in the treatment of relapsing-remitting multiple sclerosis (RRMS).

DAC HYP selectively binds to a subunit of CD25 that is exuberantly expressed on T-cells that become abnormally activated in MS [Perry JSA et al. Sci Transl Med. 2012; Wuest SC et al. Nat Med. 2011; Martin JF et al. J Immunol. 2010; Bielekova B et al. Proc Natl Acad Sci USA. 2004; McDyer JF et al. J Immunol. 2002]. DAC HYP modulates interleukin-2 signaling without causing general immune cell depletion.

DECIDE was designed to determine if DAC HYP would provide superior outcomes for identified clinical end points compared with IFN-β-1a in greater than 1800 people with RRMS in 28 countries randomized to treatment with subcutaneous DAC HYP 150 mg every 4 weeks (n = 919) or intramuscular injection of IFN-β-1a 30 μg QW (n = 922). The primary end point was the reduction in annualized relapse rate (ARR). Secondary end points included the number of new or newly enlarging T2 hyperintense lesions on magnetic resonance imaging (MRI), the proportion of patients with sustained disability progression as determined by Extended Disability Severity Scale (EDSS) scores, the proportion of relapse-free patients, and a worsening physical impact score on the MS Impact Scale (MSIS-29).

Baseline demographic and clinical characteristics (duration of RRMS, relapses in previous year, EDSS score, prior treatment, the presence and number of gadolinium-enhancing [Gd+] lesions, and T2 lesions) were similar in both study arms.

The primary end point was met. ARR in the DAC HYP arm was 45% less than in the IFNβ-1a arm (0.216 vs 0.393; 95% CI, 35.5% to 53.1%; P < .0001). Significantly, more patients receiving DAC HYP remained relapse-free throughout the trial (overall RR 41%, P < .0001), with increasing divergence between the arms with time.

Week 96 MRI data revealed a reduction in the mean number of new and newly enlarged T2 lesions with DAC HYP (9.4 with IFN-β-1a, n = 841 vs 4.3 with DAC HYP, n = 864; 54% reduction), new Gd+ lesions (1.0 with IFN-β-1a, n = 909 vs .4 with DAC HYP, n = 900; 65% reduction), and new T1 hypointense lesions (4.4 with IFN-β-1a, n = 908 vs 2.1 with DAC HYP, n = 899; 52% reduction; all P < .0001).

Confirmed disability progression was lower in the DAC HYP arm vs IFN-β-1a, with a risk reduction of 16% (P = .16) at 3 months in patients with suspected disease progression and 27% (P = .0332) at 6 months in patients with confirmed disease progression; a similar pattern was seen in patients with suspected and confirmed progression with further divergence of the study arms out to week 144. More patients treated with IFN-β-1a than with DAC HYP had MSIS-29 scores that were indicative of a clinically meaningful worsening of symptoms (23% vs 19%; 24% reduction; P = .0176). Finally, annualized brain volume change for weeks 0 to 24 and weeks 24 to 96 was lower with DAC HYP (0.67%; P = .0325 and 0.52%; P < .0001, respectively) vs IFN-β-1a (0.74% and 0.56%, respectively).

The number of adverse events and discontinuation rate were comparable in both arms. DAC HYP was associated with more overall serious adverse events (n = 40, 4%) than IFN-β-1a (n = 15, 2%), with more serious cutaneous events (n = 14, 2% vs n = 1, < 1%), and with more hepatic laboratory abnormalities (n = 59, 6% vs n = 31, 3%). These were manageable with standard monitoring and medical interventions. Discontinuation due to adverse events was higher in the DAC HYP arm (130, 14% vs 81, 9%), whereas the number of deaths was less (4 vs 1).

The researchers concluded that the DECIDE findings support the potential of DAC HYP as a once-monthly option for the treatment of patients with RRMS.

• © 2014 MD Conference Express®