Table 1.
Pivotal clinical trials of IM IFN β in MS
| Study | Design | Treatment | Patients | Study duration | Key data | References |
|---|---|---|---|---|---|---|
| IT study of IFN β | Multicenter, randomized, open-label, PBO controlled | IFN β 106 IRU/m2 at each lumbar puncture semiweekly for the first 4 weeks and once per month for the next 5 months | MS (n = 20) |
IFN β: 1.8–2.0 years PBO: 1.5–1.7 years |
Patients who received IT IFN β (mean follow-up time 1.5 years) were more likely to show improvement in their clinical condition than those who received PBO (mean follow-up time 1.2 years; p < 0.036) | Jacobs et al. (1981) [44] |
| MSCRG | Multicenter, randomized, double blinded, PBO controlled | IFN β-1a 30 µg IM QW for up to 104 weeks | RMS (n = 301) | 104 weeks |
Clinical outcomes: Over 104 weeks, the time to 6-month CDW was greater in patients treated with IM IFN β-1a (n = 158) than with PBO (n = 143; p = 0.02). At 104 weeks, the estimated proportion of patients with 6-month CDW was 21.9% with IM IFN β-1a and 34.9% with PBO. In patients followed for ≥104 weeks, the ARR was 0.61 with IM IFN β-1a and 0.90 with placebo (p = 0.002) MRI outcomes: After 1 year of treatment, IM IFN β-1a treatment caused greater reductions than PBO in the number (67.2% vs 31.5% reduction; p = 0.02) and volume (72.5% vs 55.9% decrease; p = 0.02) of Gd+ lesions. Differences were sustained over 2 years of treatment (reduction in number of lesions: 74.8% vs 28.9%; p = 0.05; reduction in volume of lesions: 70.9% vs 44.1%; p = 0.03) |
Jacobs et al. (1996) [78] |
| Follow-up MRI analyses: After 2 years, IM IFN β-1a patients compared with PBO patients had a lower mean (SD) number of new or enlarging T2 lesions (3.2 [3.6] vs 4.8 [4.4]; p = 0.002) | Simon et al. (1998) [197] | |||||
| CHAMPS | Multicenter, randomized, double blinded, PBO controlled | IM IFN β-1a 30 µg QW for 3 years | Patients who had a first acute, clinical demyelinating event (n = 383) | 3 years |
Clinical outcomes: After 3 years of treatment, the estimated cumulative probability of CDMS was lower in patients treated with IM IFN β-1a (n = 193) than with PBO (n = 190; RRR 30%; RR 0.56; 95% CI 0.38–0.81; p = 0.002) MRI outcomes: At 18 months, IM IFN β-1a patients had less increase than PBO patients in the volume of T2 lesions (28 mm3 vs 313 mm3; p < 0.001), fewer new or enlarging T2 lesions (mean [SD] 2.1 [3.2] vs 5.0 [7.7]; p < 0.001), and fewer Gd+ lesions (0.14 [1.5] vs 1.4 [3.6]; p < 0.001) |
Jacobs et al. (2000) [79] |
| Subgroup analyses: Over 2 years, IM IFN β-1a had a lower estimated probability of reaching a composite endpoint of CDMS or >1 new or enlarging T2 lesions than PBO (RRR 27.2%; RR 0.47; 95% CI 0.36–0.62; p < 0.001) in the overall CHAMPS population. Analysis of patients based on the initial demyelinating event demonstrated similar estimated probabilities for the composite endpoint (optic neuritis adjusted RR 0.50 [p < 0.001]; brainstem/cerebellum adjusted RR 0.41 [p < 0.001]; spinal cord adjusted RR 0.40 [p = 0.004]); RR adjusted for T2 lesion volume and number of Gd+ lesions at baseline | Beck et al. (2002) [80] |
ARR annualized relapse rate, CDMS clinically definite multiple sclerosis, CDW confirmed disability worsening, CHAMPS Controlled High Risk Avonex Multiple Sclerosis Study, CI confidence interval, Gd+ gadolinium enhancing, IFN interferon, IM intramuscular, IRU interferon reference units, IT intrathecal, MRI magnetic resonance imaging, MS multiple sclerosis, MSCRG Multiple Sclerosis Collaborative Research Group, PBO placebo, QW once weekly, RMS relapsing multiple sclerosis, RR rate ratio, RRR relative risk reduction, SD standard deviation