"CONCLUSIONS: IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment."
Follow up as many weeks as you want and so far the follow up is already 52 weeks published and counting and Serono has not been able to claim that there is decrease in dissability.
Antegren phase II at 6 months shows a "trend" to decrease dissabilities (lack of power with 258 subjects, it will not be so with ongoing 900 subject phase III), you could be sure that if the coming interin analysis of Antegren ongoing phase III shows not a trend, but statistically proven dissabilities at one year, the filing of Antegren will be in 2004, otherwise BIIB will file on 2005.
Proven decrease in dissabilities with statistical significance is the only hurdle left for the clearance of Antegren in 2004/5 as opposed to 2005/6.
And Antegren side effects profile? what about drinking water comparison !!!
"Patients receiving 44 micro g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw."
Fewer "active lesions", very neat, but how does that compared with NEW Lesions, no mentioned, cause there is no difference. But, the ANTEGREN study is no shy about it: less than one new lesion (0.7) vs Avonex 7 to 8 new lesions (Rebif will bring about similar protection to new MRI lesions as Avonex, notice that I am mixing studies now).
Your direct side effects comparison:
"Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage. Neutralizing antibodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw."
All those side effects after PAYING 50% MORE, and hardly a long term benefit to brag about, do not believe me, then read it in the next post from Serono's own conclusions...
"The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks. RESULTS: After 24 weeks, 74.9% (254/339) of patients receiving IFNbeta-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw."
This means that Rebiff 74.9% vs 63.3% Avonex, out of each 10 subjects 1 was better for the relapse free at 24 weeks, so what that subject will relapse anyway in the next 24 weeks.
Meantime that same subject was having 3 times a week more "flu like syndrome" and more chances of skin damage and more altered liver enzymes, and altered white cells, and way excess anti-interferon antibodies (a massive Rebiff 25% vs just 2% Avonex).
"The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw."
Yes avoiding relapse is great, but when the price is to feel like
Now, read it from Serono:
"Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial.
Panitch H, Goodin DS, Francis G, Chang P, Coyle PK, O'Connor P, Monaghan E, Li D, Weinshenker B; EVIDENCE Study Group. EVidence of Interferon Dose-response: Europian North American Compartative Efficacy; University of British Columbia MS/MRI Research Group.
University of Vermont College of Medicine, Burlington, VT 05401, USA. email@example.com
BACKGROUND: Interferon beta (IFNbeta) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial. METHODS: This randomized, controlled, multicenter trial compared the efficacy and safety of IFNbeta-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFNbeta-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations."
Let's start the criticisms: Yes, Serono study has "blinded Assesors", BUT, Why did Serono start the study with OPEN assignment of the subjects to each drug, WHY NOT BLIND from the start????, try doing that with placebo and your study is label garbage.
"Geneva, Switzerland. 8 March 2002. SERONO'S REBIF� RECEIVES FDA APPROVAL"
"Geneva, Switzerland, Rockland, MA, USA, and New York, NY, USA. 11 July 2002. SERONO AND PFIZER TO CO-PROMOTE MULTIPLE SCLEROSIS TREATMENT REBIF� IN THE UNITED STATES"
More than a year after approval, more than a year after marketing, more than a year after marketing with Pfizer power...
...And still Avonex goes on to sell ONE BILLION DOLLARS.
There is your EVIDENCE trial!!!
: Clin Ther. 2003 Jan;25(1):105-18. Related Articles, Links
Clin Ther. 2003 Jun;25(6):1888-90.
Clin Ther. 2003 Jun;25(6):1890-3.
An examination of the results of the EVIDENCE, INCOMIN, and phase III studies of interferon beta products in the treatment of multiple sclerosis.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. firstname.lastname@example.org
BACKGROUND: Three interferon (IFN) beta products are currently available for the treatment of relapsing multiple sclerosis (MS). Each of these agents showed effectiveness in the treatment of MS in the respective randomized, double-blind, placebocontrolled Phase III trials. However, there have been no randomized, double-blind, placebo-controlled trials directly comparing the efficacy and safety of these formulations. OBJECTIVE: The objective of this article was to compare the results of available comparative studies with the results of the pivotal Phase III trials of each IFN beta product. METHODS: BIOSIS, Current Contents/Clinical Medicine, and MEDLINE were searched for English-language articles published from 1996 to the present comparing the efficacy and safety of IFN beta formulations in the treatment of MS. Search terms included interferon beta 1a, interferon beta 1b, and multiple sclerosis. Articles or abstracts that reported the results of Phase III trials or studies directly comparing IFN beta formulations in the treatment of relapsing or relapsing-remitting MS were included in the review. RESULTS: Seven head-to-head studies were identified that directly compared the efficacy of IFN beta products in the treatment of MS. Two of these studies- INCOMIN (Independent Comparison of Interferon) and EVIDENCE (Evidence for Interferon Dose-Effect: European-North American Comparative Efficacy)- found significant differences in clinical efficacy between IFN beta products, whereas the remaining studies showed equal clinical efficacy between products. CONCLUSION: Inconsistencies within and between the results of the reviewed studies suggest that clinicians should use caution in interpreting the findings of the INCOMIN and EVIDENCE comparative trials.
the ms controversy is laden in politics. the european market has denied their patients the use of avonex for years. only recently great britain agreed to pay bgen for the use of avonex. the europen medical structure is different from that of the united states. they have socialized medicine, essentially quite a poor environment for research and quite bad if you need state of the art medicine for relief.