Efficacy And Tolerability Of Intramuscular Interferon-beta-1a Compared With Subcutaneous Interferon-Beta-1a In Relapsing MS: Results From PROOF
Minagara A, Murray TJ; PROOF Study Investigators
Murray TJ, Arnold D, Duquette P, Jacques F, Melanson M, Oger J, Rabinovich H, Rice G, Aichner F, Ladurner G, Schautzer F, Strasser-Fuchs S, Boundy K, Butzkueven H, Hodgkinson S, King J, Macdonnell R, Pollard J, Schwartz R, Sedal L, Kachuck N, Kaufman M, Khatri B, Modell E, Minagar A, Rammohan K, Riskind P, Stephens R
Curr Med Res Opin 2008 Apr;24(4):1049-55
Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71107, USA
Benefits from Interferon-beta (IFN-ß treatment in patients with Multiple Sclerosis are affected by many factors.
Including sustained clinical efficacy, acceptable tolerability, adherence to therapy, and the development of Neutralizing AntiBodies (NABs).
The Prospective and Retrospective Long-Term Observational Study of Avonex and Rebif (PROOF) was designed to compare the relative efficacy and tolerability of the two IFN-ß-1a products for up to 5 years.
PROOF compared the relative efficacy and tolerability of IntraMuscular (IM) IFN-ß-1a (Avonex) 30 microg once weekly (n = 69) and SubCutaneous (SC) IFN-ß-1a (Rebif) 44 microg three times per week (n = 67).
The duration of the retrospective portion of the study was 12-24 months. Due to slow enrollment, PROOF ended earlier than planned and the final duration of the prospective portion of the study was 6 months.
Therefore, between 18 and 30 months of efficacy and tolerability data were available for analysis.
After controlling for baseline disability level, Expanded Disability Status Scale (EDSS) scores revealed no statistically significant differences between the treatment groups.
During the prospective portion of the study, with sustained disability progression similar in both groups (25.8% IM IFN-ß-1a 30 mug once weekly vs. 26.7% SC IFN-ß-1a 44 mug three times per week).
Relapse rates were similar in the groups, as were MRI endpoints of Brain Parenchymal Fraction, T1 lesion volume, T2 lesion volume, number of new/enlarging T2 lesions, and Gadolinium-enhancing (Gd+) lesion volume and count.
Treatment groups differed in frequency of NABs, with 19% of patients treated with SC IFN-ß-1a 44 microg three times per week NAb+ compared with none treated with IM IFN-ß-1a 30 microg once weekly.
More NAb+ patients compared with NAB- patients had disability progression (40.0% vs. 27.8%, p = NS), new or enlarging T2 lesions at the end of treatment (63.6% vs. 40.7%, p = 0.003), and Gd+ lesions after 12-24 months of treatment (36.4% vs. 15%, p = 0.001).
The IFN-ß-1a products had comparable tolerability. However, fewer patients treated with IM IFN-ß-1a 30 microg once weekly had injection-site reactions (2.9% vs. 6.0%).
Limitations of this study include its design and sample size, both of which hinder detection of differences in efficacy between IFN-ß-1a treatments.
The results of the present study show that the two IFN-ß-1a products have comparable efficacy and differing Immunogenicity.
Subcutaneous Recombinant Interferon-beta-1a (Rebif): A Review Of Its Use In Relapsing/Remitting Multiple Sclerosis
Murdoch D, Lyseng-Williamson KA
Adis International Limited, Auckland, New Zealand
Subcutaneous recombinant Interferon-beta-1a (Rebif) 22 or 44 microg three times weekly is a valuable option in the first-line treatment in patients with Relapsing/Remitting Multiple Sclerosis (RRMS).
It has shown benefits on outcome measures related to relapses, progression of disability and Magnetic Resonance Imaging (MRI) in clinical trials.
A significant efficacy advantage for subcutaneous Interferon-beta-1a three times weekly over intramuscular Interferon-beta-1a 30 microg once weekly was shown at 24 and 48 weeks.
The most common adverse events are generally mild and clinically manageable.
Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous Interferon-beta-1a 44 microg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat RRMS.
A Comparison Of The Biologic Activity Of Two Recombinant IFN-ß Preparations Used In The Treatment Of Relapsing/Remitting Multiple Sclerosis
Antonetti F, Finocchiaro O, Mascia M, Terlizzese MG, Jaber A
J Interferon Cytokine Res 2002 Dec;22(12):1181-4
Instituto di Ricerca Cesare Serono, Ardea, Rome, Italy
Recent clinical trials with Interferon-beta (IFN-ß) in Relapsing/Remitting Multiple Sclerosis (RRMS) have clearly demonstrated that the IFN-ß dosing regimen affects the clinical efficacy.
Thereby highlighting the importance of determining the relative biologic activities of the IFN-ß products currently available.
Although studies have been published that examine the biologic activities of the two structurally different forms of recombinant IFN-ß, IFN-ß-1a (Rebif), Serono, Geneva, Switzerland) and IFN-ß-1b (Betaseron)/Betaferon), Berlex [Montville, NJ]/Schering [Berlin, Germany]), there have been few direct comparative studies.
Therefore, to obtain a more accurate estimate of the relative biologic activities of Rebif and Betaseron, this study examined the AntiViral activities of these two products within the same assay system and against the same natural human IFN-ß standard.
Whereas the manufacturers' information suggests that the BioActivity of Betaseron is only about 8.7-fold less than that of Rebif:
The results of the present direct, comparative study show that Rebif has an AntiViral activity 14 times greater than that of Betaseron.
This may have important clinical implications, because on the basis of the results reported here, Rebif at 44 microg t.i.w. is approximately double the maximal licensed weekly dose for Betaseron.