Daclizumab phase-II results
Posted: Thu Feb 18, 2010 7:21 pm
Add-On Daclizumab (Zenapax) may reduce MS disease activity more than Interferon Beta alone
ZenapaxAdd-on daclizumab treatment might reduce multiple sclerosis disease activity more than standard interferon beta treatment alone, according to a study published online first and appearing in the April edition of The Lancet Neurology.
Daclizumab has reduced multiple sclerosis disease activity in previous non-randomised studies. In the current study, John W. Rose, MD, Neurovirology Research Laboratory, VA Medical Center, Salt Lake City, Utah and colleagues aimed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving standard interferon beta treatment.
The international, multicentre, phase 2 study randomised 230 patients with active relapsing multiple sclerosis who were taking interferon beta to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks (interferon beta and high-dose daclizumab group; n = 75), daclizumab 1 mg/kg every 4 weeks (interferon beta and low-dose daclizumab group; n = 78), or interferon beta and placebo for 24 weeks (n = 77).
The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain magnetic resonance imaging (MRI) scans every 4 weeks between weeks 8 and 24. Effects of daclizumab on prespecified subsets of immune system cells and immune system response were assessed in an exploratory substudy.
The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta/placebo group compared with 1.32 in the interferon beta plus high-dose daclizumab group and 3.58 in the interferon beta plus low-dose daclizumab group.
In the substudy, daclizumab was not associated with significant changes in absolute numbers of T cells, B cells or T-cell proliferative response compared with interferon beta alone. The number of CD56bright natural killer cells was 7 to 8 times higher in both daclizumab groups than in the interferon beta/placebo group. Common adverse events were equally distributed across groups.
"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," the authors wrote. "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."
"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 accompanying comment, Olaf Stüve, MD, and Benjamin M. Greenberg, MD, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, said: "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."
Source: Doctors Guide Channels (c) 1995-2010 Doctor's Guide Publishing Limited. (16/02/10)
ZenapaxAdd-on daclizumab treatment might reduce multiple sclerosis disease activity more than standard interferon beta treatment alone, according to a study published online first and appearing in the April edition of The Lancet Neurology.
Daclizumab has reduced multiple sclerosis disease activity in previous non-randomised studies. In the current study, John W. Rose, MD, Neurovirology Research Laboratory, VA Medical Center, Salt Lake City, Utah and colleagues aimed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving standard interferon beta treatment.
The international, multicentre, phase 2 study randomised 230 patients with active relapsing multiple sclerosis who were taking interferon beta to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks (interferon beta and high-dose daclizumab group; n = 75), daclizumab 1 mg/kg every 4 weeks (interferon beta and low-dose daclizumab group; n = 78), or interferon beta and placebo for 24 weeks (n = 77).
The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain magnetic resonance imaging (MRI) scans every 4 weeks between weeks 8 and 24. Effects of daclizumab on prespecified subsets of immune system cells and immune system response were assessed in an exploratory substudy.
The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta/placebo group compared with 1.32 in the interferon beta plus high-dose daclizumab group and 3.58 in the interferon beta plus low-dose daclizumab group.
In the substudy, daclizumab was not associated with significant changes in absolute numbers of T cells, B cells or T-cell proliferative response compared with interferon beta alone. The number of CD56bright natural killer cells was 7 to 8 times higher in both daclizumab groups than in the interferon beta/placebo group. Common adverse events were equally distributed across groups.
"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," the authors wrote. "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."
"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 accompanying comment, Olaf Stüve, MD, and Benjamin M. Greenberg, MD, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, said: "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."
Source: Doctors Guide Channels (c) 1995-2010 Doctor's Guide Publishing Limited. (16/02/10)