June 24, 2002
A major pan-European survey1,2 of over 300 neurologists in seven EC countries (France, Germany, Italy, the Netherlands, Spain, Sweden and the UK) has revealed that, on average, disease-modifying beta interferon treatment for multiple sclerosis (MS) is not initiated until a patient has experienced between four and five documented MS relapses, despite current knowledge supporting earlier treatment .3,4
However, MS experts at the European Neurological Society (ENS) meeting - taking place this week in Berlin - are predicting that this situation is set to change in the light of the recent extension of indication of AVONEXÒ (Interferon beta-1a) for high risk MS patients.
Presenting the pan-European survey findings, Professor Hans-Peter Hartung, Chair of the Department of Neurology at Heinrich-Heine University, Dusseldorf, Germany, pointed out that, while these findings show there is still some way to go before clinical practice begins to match current knowledge, they represent an improvement on the results of similar research conducted twelve months previously3, with the average number of relapses prior to treatment initiation falling over this period from 5.0 to 4.4.
"There is clearly a trend towards earlier treatment, but there continue to be barriers for prescribers to contend with" Professor Hartung said. He expressed the hope, however, that this situation should change significantly as a consequence of this year's extension of indication for AVONEX to include patients who have experienced only one attack or demyelinating event (insufficient for a conclusive diagnosis of MS) but who are judged to be at high risk of progressing to clinically definite MS. Prior to this development, disease-modifying therapy was only indicated for individuals with established Relapsing Remitting MS, in whom considerable "silent" neurological damage might already have occurred.
"The licensing of AVONEX for patients who do not even have a confirmed MS diagnosis gives prescribers an added impetus for starting treatment earlier in patients with clinically definite MS" Professor Hartung said. ****
Reviewing the data that support early intervention, Professor Frederick Munschauer, Professor of Neurology and Interim Chair at State University of New York (SUNY) at Buffalo School of Medicine, Buffalo General Hospital cited strong evidence that - in patients with a single attack - significant subclinical disease activity (as detected by CNS lesions on MRI scanning) is predictive of a progression to clinically definite MS3,4. He also cited a recent study, which showed that CNS lesion volume at this very early stage correlates with the risk of MS disability many years later4.
"We now have compelling data from the sub analysis of the CHAMPS5 trial that use of AVONEX in a high risk* patient population significantly reduces the rate of progression to clinically definite MS. This means some patients will no longer have to wait for an MS diagnosis under the traditional approach to reap the benefits of disease-modifying therapy", Dr Munschauer affirmed, adding "Importantly, AVONEX provided even greater benefit to patients who had more aggressive disease as measured by MRI * ".
In the CHAMPS5 study, 383 patients with a first demyelinating event and abnormal MRI scans were given either AVONEX (30 mcg once weekly, administered intramuscularly) or placebo for up to three years. At two years, AVONEX was found to reduce the risk of a second attack by 44% compared to placebo (p=0.002). In a post-hoc sub-group analysis of 91 particularly high-risk patients as measured by
MRI *, this risk reduction was magnified to 63% at two years **, confirming that AVONEX has even greater efficacy in the face of more subclinical disease activity.
AVONEX is the only MS disease-modifying treatment approved for use prior to a diagnosis of clinically definite MS*** and the only one for which the benefits of early treatment have been clearly established at a licensed dosage. In addition, recent four-year data - from a pan-European trial of patients with established relapsing-remitting MS6 - supports a sustained therapeutic benefit of AVONEX.
Returning to the survey findings on when clinicians in Europe initiate treatment, Professor Hartung concluded: "The clinical evidence and extension of indication for AVONEX may ultimately change usage patterns quite dramatically. Hopefully these developments will significantly accelerate the natural shift towards earlier treatment that we are currently seeing".
"High risk" is defined as =9 hyperintense T2 lesions plus =1 gadolinium-enhancing lesion
** Based on Kaplan Meier estimates of the cumulative probability of developing clinically definite MS at two years (21% in Avonex-treated patients vs 56% in placebo patients).
*** AVONEX (30 mcg i.m. once weekly) is now indicated for the treatment
of patients who have experienced a single demyelinating event:
with an active inflammatory process
severe enough to warrant treatment with intravenous corticosteroids
if alternative diagnoses have been excluded
if they are determined to be at high risk of developing clinically definite MS
**** Clinical Definite Multiple Sclerosis is defined as the occurrence
of a second attack of MS.
Champs - (Controlled High Risk Subjects AVONEX Multiple Sclerosis Prevention Study)
MS Research Monitor: MS in Europe - Phase 9. March 2002
MS Research Monitor: MS in Europe - Phase 7. March 2001
O'Riordan JI et al. Brain 1998; 12: 495-503
Brex et al. N Engl J Med 2002; 346:158-64.
Jacobs LD et al. N Engl J Med 2000; 343: 898-904
Kappos et al, Neurology, 2002; 58(suppl3) A460
SOURCE: Forest Laboratories, Inc.
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