36096
document
Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis : a multicentre , randomised , double-blind , placebo-controlled phase IIb study . BACKGROUND A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions . We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind , placebo-controlled phase IIb study . METHODS The study was done in 51 centres in nine countries . Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing ( GdE ) lesion on screening MRI . Of 720 patients screened , 306 eligible patients were enrolled . Patients , aged 18-50 years , were randomly assigned to placebo ( n=102 ) , laquinimod 0.3 mg a day ( n=98 ) , or 0.6 mg a day ( n=106 ) . Brain MRI scans and clinical assessments were done at week -4 , baseline , and monthly from week 12 to week 36 . The primary outcome was the cumulative number of GdE lesions at weeks 24 , 28 , 32 , and 36 . The principal analysis of the primary endpoint was done on the intention-to-treat cohort . This study is registered with ClinicalTrials.gov , number NCT00349193 . FINDINGS Compared with placebo , treatment with laquinimod 0.6 mg per day showed a 40.4 % reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans ( simple means 4.2 [ SD 9.2 ] vs 2.6 [ 5.3 ] , p=0.0048 ) ; treatment with 0.3 mg per day showed no significant effects ( 3.9 [ 5.5 ] vs placebo , p=0.6740 ) . Both doses of laquinimod were well tolerated , with some transient and dose-dependent increases in liver enzymes . A case of Budd-Chiari syndrome-ie , a thrombotic venous outflow obstruction of the liver-occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0.6 mg laquinimod . Anticoagulant treatment resulted in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation . INTERPRETATION In patients with relapsing-remitting multiple sclerosis , 0.6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated .
36097
Intervention_Pharmacological
laquinimod
36098
Intervention_Pharmacological
laquinimod
36099
Intervention_Pharmacological
laquinimod
36100
Intervention_Control
placebo
36101
Intervention_Pharmacological
laquinimod
36102
Outcome_Physical
MRI-monitored disease activity
36103
Outcome_Physical
active lesions
36104
Outcome_Physical
MRI-monitored disease
36105
Outcome_Physical
gadolinium enhancing ( GdE ) lesion
36106
Outcome_Physical
Brain MRI scans and clinical assessments
36107
Outcome_Physical
cumulative number of GdE lesions
36108
Outcome_Physical
cumulative number of GdE lesions per scan
36109
Outcome_Physical
liver enzymes
36110
Outcome_Adverse-effects
Budd-Chiari syndrome-ie
36111
Outcome_Adverse-effects
thrombotic venous outflow obstruction of the liver-occurred
36112
Outcome_Physical
liver enzymes
36113
Outcome_Physical
hepatic decompensation
36114
Outcome_Physical
MRI-measured disease activity
36115
Participant_Condition
relapsing-remitting multiple sclerosis
36116
Participant_Condition
multicentre
36117
Participant_Condition
51 centres in nine countries .
36118
Participant_Condition
one or more relapses in the year before entry and at least one gadolinium enhancing ( GdE ) lesion on screening MRI .
36119
Participant_Sample-size
306
36120
Participant_Age
18-50