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document
Daclizumab high-yield process in relapsing-remitting multiple sclerosis ( SELECT ) : a randomised , double-blind , placebo-controlled trial . BACKGROUND Daclizumab , a humanised monoclonal antibody , modulates interleukin-2 signalling by blocking the α subunit ( CD25 ) of the interleukin-2 receptor . We assessed whether daclizumab high-yield process ( HYP ) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis . METHODS We did a randomised , double-blind , placebo-controlled trial at 76 centres in the Czech Republic , Germany , Hungary , India , Poland , Russia , Ukraine , Turkey , and the UK between Feb 15 , 2008 , and May 14 , 2010 . Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned ( 1:1:1 ) , via a central interactive voice response system , to subcutaneous injections of daclizumab HYP 150 mg or 300 mg , or placebo , every 4 weeks for 52 weeks . Patients and study personnel were masked to treatment assignment , except for the site pharmacist who prepared the study drug for injection , but had no interaction with the patient . The primary endpoint was annualised relapse rate . Analysis was by intention to treat . The trial is registered with ClinicalTrials.gov , number NCT00390221 . FINDINGS 204 patients were assigned to receive placebo , 208 to daclizumab HYP 150 mg , and 209 to daclizumab HYP 300 mg , of whom 188 ( 92 % ) , 192 ( 92 % ) , and 197 ( 94 % ) , respectively , completed follow-up to week 52 . The annualised relapse rate was lower for patients given daclizumab HYP 150 mg ( 0·21 , 95 % CI 0·16-0·29 ; 54 % reduction , 95 % CI 33-68 % ; p < 0·0001 ) or 300 mg ( 0·23 , 0·17-0·31 , 50 % reduction , 28-65 % ; p=0·00015 ) than for those given placebo ( 0·46 , 0·37-0·57 ) . More patients were relapse free in the daclizumab HYP 150 mg ( 81 % ) and 300 mg ( 80 % ) groups than in the placebo group ( 64 % ; p < 0·0001 in the 150 mg group and p=0·0003 in the 300 mg group ) . 12 ( 6 % ) patients in the placebo group , 15 ( 7 % ) of those in the daclizumab 150 mg group , and 19 ( 9 % ) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse . One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess . INTERPRETATION Subcutaneous daclizumab HYP administered every 4 weeks led to clinically important effects on multiple sclerosis disease activity during 1 year of treatment . Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease . FUNDING Biogen Idec and AbbVie Biotherapeutics Inc .
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Intervention_Pharmacological
Daclizumab
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
Daclizumab
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Intervention_Control
placebo
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Intervention_Pharmacological
daclizumab
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Intervention_Pharmacological
daclizumab
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Intervention_Pharmacological
daclizumab
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Intervention_Pharmacological
daclizumab
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Intervention_Pharmacological
daclizumab
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Outcome_Physical
relapsing-remitting multiple sclerosis
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Outcome_Other
annualised relapse rate
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Outcome_Other
relapse
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Participant_Condition
relapsing-remitting multiple sclerosis ( SELECT ) :
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Participant_Condition
patients with relapsing-remitting multiple sclerosis
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Participant_Age
aged 18-55 years
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Participant_Condition
relapsing-remitting multiple sclerosis
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Participant_Sample-size
204 patients
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Participant_Condition
assigned to receive placebo
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Participant_Condition
daclizumab HYP 150 mg
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Participant_Condition
daclizumab
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Participant_Condition
treatment option for relapsing-remitting