Abstract
Background
Monoclonal antibodies such as daclizumab could be a possible alternative immunotherapy to interferon beta treatment in people with multiple sclerosis (MS). It blocks the interleukin-2 receptor alpha subunit (CD25), and seems to be beneficial to patients with relapsing remitting multiple sclerosis (RRMS) in clinical and magnetic resonance imaging (MRI) measures of outcomes.
This is an update of a Cochrane review first published in 2010, and previously updated in 2012.
Objectives
To assess the safety of daclizumab and its efficacy to prevent clinical worsening in patients with RRMS.
Search methods
The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (17 May 2013). We handsearched the references quoted in the identified trials and reports (May 2013) from the most important neurological associations and MS societies. We contacted researchers participating in trials on daclizumab.
Selection criteria
All randomised controlled clinical trials (RCTs) evaluating daclizumab, alone or combined with other treatments versus placebo, or any other treatment for patients with RRMS.
Data collection and analysis
Two review authors independently assessed references retrieved for possible inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality. We resolved any disagreements by consensus among review authors.
Main results
We included two trials with 851 patients that evaluated the efficacy and safety of daclizumab versus placebo for RRMS. We judged them to be at low risk of bias. Due to different time point evaluations and available data on primary studies, we were unable to undertake a meta-analysis. At 24 weeks, the median change was 0 (range -2 to 3) in the interferon beta and placebo group, 0 (-2 to 4) in the interferon beta and low-dose daclizumab group and 0 (-2 to 2) in the interferon beta and high-dose daclizumab group in 230 participants. The proportion of patients who had new clinical relapses were the following: 16 patients (21%) in the interferon beta and high-dose daclizumab group, 19 (24%) in the interferon beta and low-dose daclizumab group and 19 (25%) in the interferon beta and placebo group had relapses (P value = 0.87). At 52 weeks, the changes in Expanded Disability Status Scale (EDSS) from baseline was 0.09 ± 0.71 in placebo group, -0.08 ± 0.52 in low-dose daclizumab group and 0.05 ± 0.61 in high-dose daclizumab group in 621 participants. There was a significant difference between placebo and low-dose daclizumab groups (P value = 0.01), but no significant difference between placebo and high-dose daclizumab groups (P value = 0.49). The proportion of patients with new relapsing MS was significantly reduced in both daclizumab groups (19% in low-dose daclizumab group, 20% in high-dose daclizumab group) compared with placebo group (36%) (P value < 0.0001 and P value = 0.00032, respectively). There was no increased number of patients in any adverse events (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07) or serious adverse events in daclizumab groups compared with placebo (RR 1.15, 95% CI 0.29 to 4.54). Infections were the most frequent adverse events in treated participants and were resolved with standard therapies. One trial was still ongoing.
Authors’ conclusions
There was insufficient evidence to determine whether daclizumab was more effective than placebo in patients affected by RRMS in terms of clinical and MRI measures of outcomes. Daclizumab appeared to be relatively well tolerated. Infections were the most frequent adverse events, and were resolved with standard therapies.
Plain language summary
Daclizumab, an antibody, as possible alternative therapy to interferon beta in people with relapsing remitting multiple sclerosis
Background
Monoclonal antibodies such as daclizumab could be a possible alternative immunotherapy to interferon beta treatment in people with multiple sclerosis. This is an update of a Cochrane review first published in 2010, and previously updated in 2012. In this review, we aimed to evaluate the effectiveness and safety of daclizumab, alone or combined to other treatments for the improvement in relapsing remitting multiple sclerosis.
Study characteristics
To test the efficacy we measured the disability changes and the proportion of patients who had new relapses, while to test the safety we took into account the number of patients who exhibited any type of adverse events. We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment group) comparing daclizumab, alone or with other treatments versus placebo (a pretend treatment). Patients were aged 18 to 65 years with relapsing remitting multiple sclerosis. Evidence is current to May 2013.
Key results
We found two studies (funded by Facet Biotech/Biogen Idec and Biogen Idec/AbbVie Biotherapeutics Inc), which met our inclusion criteria, with 851 patients, both male and female, aged 18 to 65 years. The results did not provide sufficient evidence on the effectiveness of daclizumab, and further studies are needed. One study is still ongoing. Daclizumab was generally well-tolerated, the most frequent adverse events being infections, which were all resolved with standard therapies. In order to have more clear results, the length of follow-up (where the patients are observed and monitored following treatment) needs to be longer.
Quality of the evidence
We considered both studies to be of high quality.
