Add-On Daclizumab Treatment May Be Better In Reducing Multiple Sclerosis Disease Activity Than Interferon Beta Alone

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Main Category: Multiple Sclerosis
Also Included In: Clinical Trials / Drug Trials
Article Date: 16 Feb 2010 - 0:00 PDT

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An article published Online First and in the April edition of The Lancet Neurology reports that add-on daclizumab treatment might reduce multiple sclerosis disease activity more than standard interferon beta treatment alone. The article is the work of Dr John W Rose, Neurovirology Research Laboratory, VA Medical Center, Salt Lake City, Utah and University of Utah, USA, and colleagues.

Daclizumab is a humanised monoclonal antibody. It is a genetically engineered antibody with a human structure and specific binding sites. Daclizumab has reduced multiple sclerosis disease activity in earlier non-randomised studies. The authors aimed in this new study to investigate whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving standard interferon beta treatment.

Fifty-one centres in the USA, Canada, Germany, Italy, and Spain took part in this phase 2, randomised study. Patients with active relapsing multiple sclerosis who were taking interferon beta were randomly assigned to different groups:

• interferon beta and high-dose daclizumab group: received add-on subcutaneous daclizumab 2 mg/kg every two weeks
• interferon beta and low-dose daclizumab group: received daclizumab 1 mg/kg every four weeks
• interferon beta and placebo group, for twenty-four weeks

The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain MRI scans every four weeks between weeks eight and twenty-four. This indicates multiple sclerosis disease activity. Effects of daclizumab on pre-specified subsets of immune system cells and immune system response were assessed in an exploratory sub-study.

A total of 230 patients were randomly assigned to receive interferon beta and high-dose daclizumab (n=75), interferon beta and low-dose daclizumab (n=78), or interferon beta and placebo (n=77). The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4•75 in the interferon beta and placebo group compared with 1•32 in the interferon beta and high-dose daclizumab group and 3•58 in the interferon beta and low-dose daclizumab group. In the sub-study, daclizumab was not related with significant changes in absolute numbers of T cells, B cells, or natural killer cells, or T-cell proliferative response compared with interferon beta alone. The number of CD56bright natural killer cells was seven to eight times higher in both daclizumab groups than in the interferon beta and placebo group. Common adverse events were similar across groups.

The authors explain: "This study provides confirmatory data that daclizumab treatment causes an expansion of CD56bright natural killer cells and adds support to the theory that expansion of CD56bright natural killer cells might mediate some of the effects of daclizumab on reducing multiple sclerosis lesion activity. In addition to the results of previous trials of daclizumab in multiple sclerosis, several lines of evidence have suggested a potential immunoregulatory function for CD56bright natural killer cells: they are expanded during conditions of natural immune tolerance - for example, pregnancy."

They write in conclusion: "This randomised controlled trial indicates that daclizumab can reduce new lesion formation in relapsing multiple sclerosis compared with interferon beta alone...Multiple sclerosis treatments that have the potential to improve in risk - benefit ratios when compared with available treatments are needed; thus, additional studies to define the long-term clinical risks and benefits of daclizumab are warranted."

In an associated note, Dr Olaf Stüve, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA and Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA, and Dr Benjamin M Greenberg Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA, comment: "All clinical and paraclinical evidence suggests that daclizumab mediates its beneficial effects at least partly through expanding regulatory CD56bright natural killer cells. It might now be time to explore further how these cells can be expanded in patients by other means... Identifying the physiological mechanism or mechanisms that lead to the expansion of these cells during disease remission might prove crucial in further understanding disease mechanisms and in developing novel therapeutics."

"Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind,placebo-controlled, add-on trial with interferon beta"
Daniel Wynn, Michael Kaufman, Xavier Montalban, Timothy Vollmer, Jack Simon, Jacob Elkins, Gilmore O'Neill, Lauri Neyer, James Sheridan, Chungchi Wang, Alice Fong, John W Rose; for the CHOICE investigators
DOI: 10.1016/S1474-4422(10)70033-8
The Lancet Neurology

Written by Stephanie Brunner (B.A.)
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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