Table 3.
Comparison of currently available data on interferon β-1a and pegylated interferon β-1a
| IFNβ-1a aPRISMS: 2-year study24 | PEG-IFNβ-1a aADVANCE: 1-year study 5 | |||||
|---|---|---|---|---|---|---|
| Administration | Placebo SC; TIW | 22 µg SC; TIW | 44 µg SC; TIW | Placebo SC; Q2W | 125 µg SC; Q2W | 125 µg SC; Q2W |
| Number of patients enrolled | 187 (170) | 189 (167) | 184 (165) | 500 (456) | 512 (438) | 500 (438) |
| % Completed treatment | 91 | 88 | 90 | 91 | 86 | 88 |
| Clinical outcomes | ||||||
| Relapse rateb | 2.56 | 1.82 | 1.73 | 0.40 | 0.26 | 0.29 |
| % reduction of relapse rate vs placebo | – | 27 | 33 | – | 36 | 28 |
| % relapse free (1 year) | 22 | 37 | 45 | 71 | 81 | 78 |
| Disability progressionc | 0.48 | 0.23 | 0.24 | 0.105 | 0.068 | 0.068 |
| MRI outcomes | ||||||
| Burden of diseased | 10.9% | −1.2% | −3.8% | 0.77 cm3 | −0.26 cm3 | 0.06 cm3 |
| T2 new/enlarging lesions | 4.5 | 1.3 | 0 | 10.9 | 3.6 | 7.9 |
| T1 Gd-enhancing lesions | 8.0 | 1.4 | 1.3 | 1.4 | 0.2 | 0.9 |
| New active lesionse | 10.6 | 2.1 | 1.3 | 11.2 | 3.7 | 7.3 |
| NAbs | – | Anti-IFN: 23.8% | Anti-IFN: 12.5% | – | Anti-IFN: <1%f anti-PEG: 6%f |
Anti-IFN: <1%f anti-PEG: 8%f |
| Adverse events (%)g | ||||||
| Injection-site reactions | 22 | 61 | 62 | 7 | 62 | 56 |
| Influenza-like illness | 24 | 25 | 27 | 13 | 47 | 47 |
| Headache | 44 | 47 | 45 | 33 | 44 | 41 |
| Fatigue | 16 | 14 | 19 | 10 | 10 | 11 |
| Myalgia | 8 | 13 | 14 | 6 | 19 | 19 |
| Fever | 6 | 13 | 12 | 15 | 45 | 44 |
| Abnormal blood cell counts | ||||||
| Leukopenia | 2 | 4 | 8 | 1 | 7 | 4 |
| Lymphopenia | 4 | 5 | 13 | 3 | 5 | 4 |
| Elevated liver enzymes | ||||||
| Alanine aminotransferase | 1 | 5 | 7 | 1 | 2 | 2 |
| Aspartate aminotransferase | 1 | 2 | 3 | 1 | 1 | 1 |
| Adverse events resulting in discontinuation | 1 | 3 | 5 | 1 | 5 | 5 |
| Pharmacokinetics62 | ||||||
| AUCh | – | 12 IU⋅h/mL | 71.6 IU⋅h/mL | – | 24.5 ng⋅h/mL | 23.5 ng⋅h/mL |
| Cmax | – | 1.3 IU/mL | 12.8 IU/mL | – | 221 pg/mL | 202 pg/mL |
| Tmax (h) | – | 1–2 | 0.25 | – | 35.9 | 35.1 |
| half-life (h) | – | n.a. | 12.8 | – | 62.8 | 56.8 |
Notes:
Comparison of placebo-controlled studies; no head-to-head trials have directly compared IFNβ-1a to PEG-IFNβ-1a.
Defined as number of relapses over 2-year study period (PRISMS) or ARR at 48 weeks (ADVANCE).
Defined as change in EDSS over duration of study (PRISMS) or proportion of patients with 12-week sustained progression in EDSS ≥1.0 (ADVANCE).
Defined as change in total in T2 lesion volume from baseline (PRISMS, mm2; ADVANCE, cm3).
Defined as the sum of T1 Gd-enhancing and new or newly enlarging T2 lesions (PRISMS, clinically unique; ADVANCE new active).
Reported at 2 years.122
PRISMS reported adverse events in first 3 months of therapy and ADVANCE reported adverse events over the full 48 weeks.
Measured over 8 h for 22 µg IFNβ-1a and measured over 168 h for 44 µg IFNβ-1a and 125 µg PEG-IFNβ-1a. Cmax, maximum serum concentration; Tmax, time to reach Cmax.
Abbreviations: ARR, annualized relapse rate; AUC, area under curve; EDSS, Expanded Disability Status Scale; IFN, interferon; Q2W, once every 2 weeks; MRI, magnetic resonance imaging; n.a., not available; NAbs, neutralizing antibodies; PEG, polyethylene glycol; SC, subcutaneous; TIW, three times weekly.