DECIDE: Daclizumab cuts MS relapse rate by 45%

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]

WASHINGTON – Treatment with daclizumab high-yield process, a first-in-class interleukin-2 immunomodulator administered subcutaneously once a month, was significantly more effective on various outcomes in relapsing-remitting multiple sclerosis than was interferon beta-1a therapy during 96-144 weeks of treatment in the international DECIDE study.

The efficacy of daclizumab high-yield process (DAC HYP) was consistently superior to once-weekly intramuscular interferon (IFN) beta-1a “across key clinical, radiographic, and patient-reported MS outcome measures,” with a 45% reduction in the annualized relapse rate over that period, Dr. Ludwig Kappos said at the annual meeting of the American Academy of Neurology.

DAC HYP “has the potential to be a new once-monthly treatment option for patients with relapsing MS,” said Dr. Kappos, chair of neurology at University Hospital Basel and one of the DECIDE study investigators. Dr. Kappos serves as chair of the study’s advisory committee.

Treatment was associated with an increased risk of infections, cutaneous adverse effects, and hepatic enzyme abnormalities, which he said were “manageable with standard monitoring and medical interventions.”

DAC HYP is a humanized monoclonal antibody that selectively blocks the high-affinity interleukin-2 (IL-2) receptor subunit (CD25), which is expressed at high levels on T cells that are abnormally activated in MS. The biological effects of CD25 blockade include the inhibition of activated T cell responses and “normalization of lymphoid tissue inducer cell numbers,” he said.

The DECIDE study randomized 919 patients to treatment with 150 mg of DAC HYP administered subcutaneously once every 4 weeks and 922 patients to treatment with 30 mcg of IFN beta-1a (Avonex) administered intramuscularly once a week. Mean age of the patients was 36 years, 68% were women, and they had been diagnosed with MS for a mean of 5 years. Patients in both groups had had a similar mean number of relapses within the previous year (0.7-0.8); 21% had highly active MS, and 41% had been on disease-modifying treatments previously; their mean Expanded Disability Status Scale (EDSS) score was 1.2-1.3.

The study ended when the last patient had been treated for 2 years. In both arms, 29%-30% discontinued treatment, and adverse events were higher in the DAC HYP-treated group (14% vs. 9%).

During 96-144 weeks, the annualized relapse rate – the primary endpoint – was 0.393 among those on IFN beta-1a, vs. 0.216 among those on DAC HYP, a 45% reduction that was highly statistically significant (P < .0001), Dr. Kappos said.

Secondary endpoints included the proportion who remained relapse free, which was higher among those on DAC HYP at different points during the study (including 73% vs. 59% at week 96, and 67% vs. 51% at week 144). The risk of relapse was reduced by 41% (P < .0001).

Other secondary endpoints were MRI-defined lesions at week 96: The number of new or newly enlarging T2 hyperintense lesions at that point was reduced by 54%, compared with IFN beta-1a (P < .0001). There were similar reductions in new T1 hypointense lesions (black holes), which were reduced by 52% (P < .0001), and in gadolinium-enhancing lesions, which were reduced by 65% (P < .0001). There was a significant effect of treatment on brain volume over time, which was possible to detect because the study was so large, Dr. Kappos said.

At 3 months, the risk of progression was reduced by 16% among those on DAC HYP, compared with those on IFN beta-1a (P = .16), a favorable effect, although not statistically significant. At 6 months, the risk was reduced by 27% (P = .033), Dr. Kappos reported. The proportion of patients with a clinically meaningful worsening in patient-reported physical impact of MS (defined by at least a 7.5 point drop on the MSIS-29 PHYS) was reduced by 24% over those on IFN beta-1a, which was not statistically significant.

The incidence of any type of adverse event was 91% in both groups, and infections, cutaneous events, and hepatic abnormalities were more common among those treated with DAC HYP. Serious adverse events were higher among those on DAC HYP (24% vs. 21%); when MS relapses were excluded, the rate was 15% vs. 10%. Treatment discontinuations due to an adverse event, other than an MS relapse, was 14% among those on DAC HYP vs. 9% of those on IFN beta-1a. There were five deaths, one in a patient on the study drug and four among those on the comparator.

The rate of infectious adverse events was higher among those on DAC HYP (65% vs. 57%), as was the rate of serious infectious adverse events (4% vs. 2%). Cutaneous events were more common among those on DAC HYP (37% vs. 19%), as were serious cutaneous adverse events (2% vs. less than 1%).

Dr. Kappos said that hepatic abnormalities were more common among those on DAC HYP, but were reversible. The rate of ALT/AST greater than five times the upper limit of normal (ULN) was 6% among those on the DAC HYP vs. 3% among those on IFN beta-1a; but the rate of ALT greater than three times the ULN and total bilirubin more than twice the ULN was less than 1% in each group. There was one case that met the “Hy’s law” criteria in each group.

Biogen Idec and AbbVie Biotherapeutics funded the study. Dr. Kappos disclosed that University Hospital Basel has received research support from steering committee/consulting fees, and speakers fees from pharmaceutical companies that include Biogen.

[email protected]