Gold R et al. Define Investigators. Placebo-controlled phase 3 study of oral BG12 for relapsing multiple sclerosis. NEJM 367:1098-1107 , 2012
Fox et al. CONFIRM investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. NEJM 2012; 367: 1087-1097.
DEFINE 1234 patients were randomized and received at least one dose of meds (BG 12 , 240 bid, BG 12 240 tid, or placebo), about 400 per group. Primary endpoint was number with relapse at 2 years. Secondary endpoints were ANNUALIZED RELAPSE RATE, TIME TO CONFIRMED PROGRESSION OF DISABILITY, AND MRI FINDINGS.
Results favored BG-12. Percent with relapses were 27 and 26 % in two BG 12 groups and 46 % with placebo, p<.001 for both. ARR was .17, .19, and .36 again favoring BG 12. Percent with confirmed disability was 16 %, 18 %, and 27 % respectively favoring BG 12. MRI was also better.
Patient selection: age 18-55, EDSS ranging from 0-5, one relapse clinically or by MRI in period before entry into study. 198 sites in 28 countries participated with 1:`1:1 randomization. Baseline characteristics were similar in patients. Patients could switch therapy if they completed 48 weeks of study or developed confirmed worse disability.Half in MRI study. 78 % completed study with similar rates of withdrawal in the 3 groups. Time to first relapse was 37 weeks (placebo), 87 and 91 weeks in 2 BG 12 groups.
Safety: key events were nausea, vomiting, abdominal pain, pruritus, flushing, and PROTEINURIA ( 12 %). 3 % had elevated LFT's esp first six months.
CONFIRM
1430 patients were randomized, and patient 18-55, EDSS 0-5, one relapse or MRI change before initiation into study. 1:1:1:1 groups including bid and tid BG 12, placebo and glatiramer. Study went 96 weeks. Primary endpoint was ARR, secondary endpoints were (in an MRI subcohort) new and enlarging lesions, enlarging T1 black holes, proportion of patients with relapse, and proportion with disability progression at two years. Dropout rates were higher in placebo group.
ARR was 0.22, 0.2 and 0.44 favoring BG12 against placebo, and rate was .29 for glatiramer.
Study was not powered to compare BG 12 and glatiramer. Disability was not affected significantly in any group at 24 weeks. All three non placebo groups had better outcome on MRI for new T1 black holes, number of new and enlarging lesions, and gado enhancing lesions.
Comments:
Exciting data. CANNOT compare BG 12 and glatiramer. Define but not Confirm showed benefit for disability. Both studies showed benefit on relapse rates, and MRI although MRI was subgroup analysis in both studies.
Fox et al. CONFIRM investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. NEJM 2012; 367: 1087-1097.
DEFINE 1234 patients were randomized and received at least one dose of meds (BG 12 , 240 bid, BG 12 240 tid, or placebo), about 400 per group. Primary endpoint was number with relapse at 2 years. Secondary endpoints were ANNUALIZED RELAPSE RATE, TIME TO CONFIRMED PROGRESSION OF DISABILITY, AND MRI FINDINGS.
Results favored BG-12. Percent with relapses were 27 and 26 % in two BG 12 groups and 46 % with placebo, p<.001 for both. ARR was .17, .19, and .36 again favoring BG 12. Percent with confirmed disability was 16 %, 18 %, and 27 % respectively favoring BG 12. MRI was also better.
Patient selection: age 18-55, EDSS ranging from 0-5, one relapse clinically or by MRI in period before entry into study. 198 sites in 28 countries participated with 1:`1:1 randomization. Baseline characteristics were similar in patients. Patients could switch therapy if they completed 48 weeks of study or developed confirmed worse disability.Half in MRI study. 78 % completed study with similar rates of withdrawal in the 3 groups. Time to first relapse was 37 weeks (placebo), 87 and 91 weeks in 2 BG 12 groups.
Safety: key events were nausea, vomiting, abdominal pain, pruritus, flushing, and PROTEINURIA ( 12 %). 3 % had elevated LFT's esp first six months.
CONFIRM
1430 patients were randomized, and patient 18-55, EDSS 0-5, one relapse or MRI change before initiation into study. 1:1:1:1 groups including bid and tid BG 12, placebo and glatiramer. Study went 96 weeks. Primary endpoint was ARR, secondary endpoints were (in an MRI subcohort) new and enlarging lesions, enlarging T1 black holes, proportion of patients with relapse, and proportion with disability progression at two years. Dropout rates were higher in placebo group.
ARR was 0.22, 0.2 and 0.44 favoring BG12 against placebo, and rate was .29 for glatiramer.
Study was not powered to compare BG 12 and glatiramer. Disability was not affected significantly in any group at 24 weeks. All three non placebo groups had better outcome on MRI for new T1 black holes, number of new and enlarging lesions, and gado enhancing lesions.
Comments:
Exciting data. CANNOT compare BG 12 and glatiramer. Define but not Confirm showed benefit for disability. Both studies showed benefit on relapse rates, and MRI although MRI was subgroup analysis in both studies.
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