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. 2013 Dec 23;2013(12):CD008127.
doi: 10.1002/14651858.CD008127.pub4.

Daclizumab for relapsing remitting multiple sclerosis

Jia Liu  1 , Lu-Ning Wang, Siyan Zhan, Yinyin Xia
Affiliations

Daclizumab for relapsing remitting multiple sclerosis

Jia Liu et al. Cochrane Database Syst Rev. .

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.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Safety, Outcome 1 Any adverse event.
1.2
1.2. Analysis
Comparison 1 Safety, Outcome 2 Serious adverse event.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Gold 2013 {published data only}
    1. Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, et al. Daclizumab high‐yield process in relapsing‐remitting multiple sclerosis (SELECT): a randomised, double‐blind, placebo‐controlled trial. Lancet 2013;381:2167‐75. - PubMed
Wynn 2010 {published data only}
    1. Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, et al. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double‐blind, placebo‐controlled, add‐on trial with interferon beta. Lancet Neurology 2010;9(4):381‐90. - PubMed

References to studies excluded from this review

Ali 2009 {published data only}
    1. Ali EN, Healy BC, Stazzone LA, Brown BA, Weiner HL, Khoury SJ. Daclizumab in treatment of multiple sclerosis patients. Multiple Sclerosis 2009;15(2):272‐4. - PubMed
Bielekova 2004 {published data only}
    1. Bielekova B, Richert N, Howard T, Blevins G, Markovic‐Plese S, McCartin J, et al. Humanized anti‐CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proceedings of the National Academy of Sciences of the United States of America 2004;101(23):8705‐8. - PMC - PubMed
Bielekova 2006 {published data only}
    1. Bielekova B, Catalfamo M, Scrivner SR, Packer A, Cerna M, Waldmann TA, et al. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL‐2Rα‐targeted therapy (daclizumab) in multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America 2006;103(15):5941‐6. - PMC - PubMed
Bielekova 2009 {published data only}
    1. Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, et al. Effect of anti‐CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Archives of Neurology 2009;66(4):483‐9. - PMC - PubMed
Bielekova 2011 {published data only}
    1. Bielekova B, Richert N, Herman ML, Ohayon J, Waldmann TA, McFarland H, et al. Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology 2011;77(21):1877‐86. - PMC - PubMed
Borges 2013 {published data only}
    1. Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, et al. The effect of daclizumab on brain atrophy in relapsing‐remitting multiple sclerosis. Multiple Sclerosis and Related Disorders 2013;2(2):133‐40. - PMC - PubMed
Oh 2009 {published data only}
    1. Oh U, Blevins G, Griffith C, Richert N, Maric D, Lee CR, et al. Regulatory T cells are reduced during anti‐CD25 antibody treatment of multiple sclerosis. Archives of Neurology 2009;66(4):471‐9. - PMC - PubMed
Rose 2004 {published data only}
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Rose 2007 {published data only}
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References to ongoing studies

NCT01064401 {unpublished data only}
    1. NCT01064401. Efficacy and safety of daclizumab high yield process versus interferon beta 1a in patients with relapsing remitting multiple sclerosis. www.clinicaltrials.gov/ct2/show/NCT01064401 (accessed 11 December 2013).

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References to other published versions of this review

Liu 2010
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