Table 1.
Review of natalizumab Phase III clinical trials
| Trial name | Number of patients enrolled | Type of patient enrolled | Study design | Primary outcomes | Secondary clinical outcomes | Secondary MRI outcomes | Notable adverse events |
|---|---|---|---|---|---|---|---|
| AFFIRM20 | 942 | RRMS | Randomized placebo controlled NTZ 300 mg IV every 4 weeks versus placebo infusion every 4 weeks |
1. NTZ reduced ARR by 68% at 1 year compared to placebo (P<0.001) 2. NTZ reduced the risk of sustained disability worsening at 2 years by 42% compared to placebo (P<0.001) |
1. Proportion of relapse-free patients was significantly higher in NTZ group than placebo at 1 year (77% vs 56%, P<0.001) and at 2 years (67% vs 41%, P<0.001) | 1. NTZ reduced the mean number of new/enlarging T2 lesions by 83% compared to placebo over 2 years 2. NTZ reduced the mean number of Gd+ lesions by 92% compared to placebo at years 1 and 2 |
1. Fatigue 2. Allergic reaction 3. Hypersensitivity reactions |
| SENTINEL22 | 1,171 | RRMS | Randomized placebo controlled NTZ 300 mg IV every 4 weeks + IFN-β-1a 30 µg IM weekly (combination therapy) versus IFN-β-1a 30 µg IM weekly + placebo infusion every 4 weeks |
1. Combination therapy reduced the ARR by 54% at 1 year compared to IFN-β-1a 30 µg IM + placebo (maintained at 2 years) (P<0.001) 2. Combination therapy reduced the risk of sustained disability worsening at 2 years by 24% compared to IFN-β-1a 30 µg IM + placebo (P=0.02) |
1. Proportion of relapse-free patients was significantly higher in the combination therapy group compared with IFN-β-1a 30 µg IM + placebo at 2 years (54% vs 32%, P<0.001) 2. Risk of relapse was 50% lower with combination therapy (HR 0.50; 95% CI 0.43–0.59; P<0.001) |
1. NTZ + IFN-β-1a 30 µg IM reduced the mean number of new/enlarging T2 lesions by 83% compared with IFN-β-1a 30 µg IM + placebo over 2 years 2. NTZ + IFN-β-1a 30 µg IM reduced the mean number of Gd+ lesions by 89% at 2 years compared with IFN-β-1a 30 µg IM + placebo |
1. Anxiety 2. Pharyngitis 3. Sinus congestion 4. Peripheral edema 5. PML (n=2 at the time of publication) |
| ASCEND24 | 887 | SPMS | Randomized placebo controlled NTZ 300 mg IV every 4 weeks versus placebo infusion every 4 weeks | 1. No significant difference in disability progression between the NTZ and placebo group (P=0.287) | 1. NTZ was associated with a 44% reduction of upper extremity disability (as measured on the 9HPT) compared to placebo (P=0.001) | 1. NTZ reduced the mean number of new/enlarging T2 lesions by 89% compared to placebo 2. NTZ reduced Gd+ lesions by 95% compared to placebo |
Similar to known safety profile above |
Abbreviations: MRI, magnetic resonance imaging; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IV, intravenous; NTZ, natalizumab; IFN-β-1a, interferon β-1a; IM, intramuscular; ARR, annualized relapse rate; CI, confidence interval; 9HPT, 9-hole peg test; Gd+, gadolinium-enhancing; PML, progressive multifocal leukoencephalopathy; HR, hazard ratio.