REPORT FROM ECTRIMS – BARCELONA, SPAIN – OCTOBER 7-10, 2015 – DECIDE is the second phase III trial evaluating daclizumab, an anti-CD25 monoclonal antibody that modulates IL-2 signalling. Primary results were presented at the American Academy of Neurology annual meeting (Kappos et al. AAN 2015; abstract S4.003) but are not yet published. Subjects (mean age 36 years) were randomized to subcutaneous daclizumab 150 mg q4weeks or intramuscular interferon-beta-1a for 96-144 weeks.
The annualized relapse rate (ARR) was significantly lower with daclizumab versus IFNbeta (0.216 vs. 0.393). The risk of three-month confirmed disability progression was reduced 16% with daclizumab versus active control but did not achieve statistical significance.
ARR was significantly lower (0.282 vs. 0.677) in the subgroup of patients with highly active disease, defined as >2 relapses in the year prior to study entry and >1 Gd+ lesions at baseline (Wiendl et al. ECTRIMS 2015; abstract P523). There was also a significant reduction in the mean number of Gd+ lesions with daclizumab (0.8 vs. 1.7).
The rates of no evidence of disease activity (NEDA), defined as no relapses, no new/enlarging T2 lesions and no 12-week confirmed disability progression, were 24.3% with daclizumab versus 13.9% with IFNbeta (Kappos et al. ECTRIMS 2015; abstract 528). In the phase III placebo-controlled SELECT trial, the NEDA rate at one year was 39% with daclizumab versus 11% with placebo (Havrdova et al. Mult Scler 2014;20:464-470).
Potential safety concerns with daclizumab include skin toxicities. In the SELECT trial, there was one death in a patient recovering from serious rash due to complications of a psoas abscess (Gold et al. Lancet 2013;381:2167-2175). In DECIDE, the overall incidence of cutaneous adverse events was 37% with daclizumab compared to 19% with IFNbeta (Selmaj et al. ECTRIMS 2014; abstract P094). The incidence of cutaneous effects by severity for daclizumab and IFNbeta were: moderate (38% vs. 28%); severe (3% vs. 2%); and serious (2% vs. <1%) (Kircik et al. ECTRIMS 2015; abstract P550). A majority of patients with mild (81%) or moderate (73%) cutaneous side effects received topical steroids, while patients with severe (73%) or serious 71%) cutaneous effects were treated with systemic steroids. The median duration of cutaneous adverse effects was 40.5 days for moderate skin reactions, 70.5 days for severe skin reactions, and 54.0 days for serious skin reactions.
Similar results were seen in an integrated analysis of six daclizumab studies (n=1785) (Giovannoni et al. ECTRIMS 2015; abstract P554). Cutaneous events occurred in 35%, of which 2% were considered serious. The overall incidence of serious adverse events (excluding relapse) was 16%. Elevated liver enzymes (>3 x ULN) occurred in 11%. There were two deaths (psoas abscess, autoimmune hepatitis) that may be attributable to treatment.
Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada