A J Wagstaff1, K L Goa. 1. Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Abstract
UNLABELLED: This review focuses on Rebif, one of 2 available formulations of recombinant interferon-beta-1a, a molecule with the same molecular weight and primary structure as native interferon-beta. The product under review is intended for subcutaneous injection and contains 22 or 44microg of recombinant interferon-beta-1a. This molecule has the same antiviral, antiproliferative and immunomodulatory profile as native interferon-beta. Regulation of excessive immune responses in the inflamed lesions of patients with multiple sclerosis is thought to be important to its mode of action. In vivo studies indicate that the biological response to interferon-beta-1a is sustained with 3-times-weekly, in preference to once-weekly, administration. Subcutaneous interferon-beta-1a 22 and 44microg 3 times weekly for 2 years slowed sustained progression of disability (by 6.6 and 9.4 months; first quartile), decreased the mean number (by 27 and 33%) and severity of relapses, decreased the number of hospital visits and steroid courses, and decreased the acute activity [measured as the number of new or enlarging lesions seen with magnetic resonance imaging (MRI)] and burden (measured as the cumulative area or calculated volume of the lesions) of disease in patients with relapsing-remitting multiple sclerosis. All changes (except hospital visits: significant results were obtained with the higher dose only) were significant versus placebo with both doses. A recent study of once weekly interferon-beta-1a 22 or 44microg has confirmed the dose-dependency of the clinical and MRI effects. Patients with more severe disease appear to require the higher dosage regimen. Further studies of long term (>2 years) clinical efficacy, tolerability, and pharmacoeconomic aspects are required. Although injection site disorders and alterations in liver enzymes and lymphopenia are common, they rarely lead to withdrawal from treatment. As with other interferons, an influenza-like syndrome is often seen in patients receiving interferon-beta-1a. The sustained (over 2 years) presence of neutralising antibodies has been noted in 6 to 7% of patients; 16 to 18% of patients developed neutralising antibodies at some time during 2 years of treatment. This formulation is available as powder for reconstitution, or in liquid-prefilled syringes or an autoinjector device. CONCLUSIONS: Subcutaneous interferon-beta-1a 22 to 44microg 3 times weekly dose-dependently decreases the number and severity of relapses in patients with relapsing-remitting multiple sclerosis, slows the progression of disability, and decreases lesion activity and burden of disease. This formulation offers ease of dosage adjustment and convenience of administration, and is a valuable well-tolerated and effective addition to the choice of treatments for relapsing-remitting multiple sclerosis.
UNLABELLED: This review focuses on Rebif, one of 2 available formulations of recombinant interferon-beta-1a, a molecule with the same molecular weight and primary structure as native interferon-beta. The product under review is intended for subcutaneous injection and contains 22 or 44microg of recombinant interferon-beta-1a. This molecule has the same antiviral, antiproliferative and immunomodulatory profile as native interferon-beta. Regulation of excessive immune responses in the inflamed lesions of patients with multiple sclerosis is thought to be important to its mode of action. In vivo studies indicate that the biological response to interferon-beta-1a is sustained with 3-times-weekly, in preference to once-weekly, administration. Subcutaneous interferon-beta-1a 22 and 44microg 3 times weekly for 2 years slowed sustained progression of disability (by 6.6 and 9.4 months; first quartile), decreased the mean number (by 27 and 33%) and severity of relapses, decreased the number of hospital visits and steroid courses, and decreased the acute activity [measured as the number of new or enlarging lesions seen with magnetic resonance imaging (MRI)] and burden (measured as the cumulative area or calculated volume of the lesions) of disease in patients with relapsing-remitting multiple sclerosis. All changes (except hospital visits: significant results were obtained with the higher dose only) were significant versus placebo with both doses. A recent study of once weekly interferon-beta-1a 22 or 44microg has confirmed the dose-dependency of the clinical and MRI effects. Patients with more severe disease appear to require the higher dosage regimen. Further studies of long term (>2 years) clinical efficacy, tolerability, and pharmacoeconomic aspects are required. Although injection site disorders and alterations in liver enzymes and lymphopenia are common, they rarely lead to withdrawal from treatment. As with other interferons, an influenza-like syndrome is often seen in patients receiving interferon-beta-1a. The sustained (over 2 years) presence of neutralising antibodies has been noted in 6 to 7% of patients; 16 to 18% of patients developed neutralising antibodies at some time during 2 years of treatment. This formulation is available as powder for reconstitution, or in liquid-prefilled syringes or an autoinjector device. CONCLUSIONS: Subcutaneous interferon-beta-1a 22 to 44microg 3 times weekly dose-dependently decreases the number and severity of relapses in patients with relapsing-remitting multiple sclerosis, slows the progression of disability, and decreases lesion activity and burden of disease. This formulation offers ease of dosage adjustment and convenience of administration, and is a valuable well-tolerated and effective addition to the choice of treatments for relapsing-remitting multiple sclerosis.