May 25, 2001
Findings from a European clinical trial have been published indicating that early treatment with Rebif ® (interferon beta-1a, Serono International SA, Geneva, Switzerland) is beneficial in people who are at high risk of developing clinically definite multiple sclerosis (MS).
Findings from a European clinical trial have been published indicating that early treatment with Rebif ® (interferon beta-1a, Serono International SA, Geneva, Switzerland) is beneficial in people who are at high risk of developing clinically definite multiple sclerosis (MS). This includes people who have had one neurologic episode suggesting the loss of myelin, and multiple MRI-detected lesions, or areas of myelin damage. Giancarlo Comi, MD (IRCCS Ospedale San Raffaele, Milan, Italy) and colleagues in the Early Treatment of MS Study (ETOMS) Group report results in the May 19, 2001 issue of The Lancet (Vol. 357, pp. 1576-82).
The diagnosis of clinically definite MS requires two neurological events suggesting demyelination (loss of nerve-fiber insulation) in the central nervous system separated in time and in location. Studies have shown that individuals who experience a single occurrence of a sign or symptoms of demyelination and multiple clinically “silent” magnetic resonance imaging (MRI)-detected brain lesions are at high risk for developing clinically definite MS within several years. Individuals who have similar neurologic problems but no evidence of MRI-detected lesions are at relatively low risk for developing MS over the same time period.
The ETOMS study, sponsored by Serono International SA, was designed to determine whether Rebif would delay the occurrence of another neurologic event, and thus, the onset of clinically definite MS. Additional outcomes measured included the impact of treatment on lesion activity in the brain determined by MRI scans.
Rebif is available for relapsing-remitting MS in Europe, Canada, Australia and elsewhere, but cannot currently be marketed in the U.S. because of the orphan drug status of Avonex ® (interferon beta-1a, Biogen, Inc., Cambridge, MA). FDA regulations provide a 7-year market protection for new drugs found to be effective for rare or “orphan” disorders to help stimulate investment by pharmaceutical companies in such disorders. Avonex is currently protected from market competition until mid-2003, unless the FDA determines that Rebif or another interferon beta-1a is clinically superior.
Individuals between 18-40 years of age were eligible for this study if they had had a first neurologic episode in the previous 3 months, one or more abnormalities evident during the neurological examination, and MRI scans showing multiple brain lesions. The 308 participants (from 14 European countries involving 57 medical centers) were randomly assigned to receive either a low dose (22 micrograms) of Rebif or placebo injected under the skin weekly for two years. Neurological and clinical assessments were done every six months and MRI scans were taken every 12 months. Results: The treatment did not prevent MS, but significantly reduced the rate of development of clinically definite MS, delayed the conversion to definite MS, and reduced accumulation of new MRI-detected lesions in the brain. Specifically, fewer patients on Rebif developed clinically definite MS (34%) than in the placebo group (45%) during the study time. The number of new lesions and the increase in the total accumulation of areas of myelin damage were significantly lower in the Rebif group.
The authors conclude that treatment with Rebif in individuals at high risk for developing MS significantly delayed the development of definite MS. These results are similar to those of the CHAMPS study group, which reported in the September 28, 2000 issue of The New England Journal of Medicine that initiating treatment with Avonex is also beneficial in people with “monosymptomatic” disease who are at high risk for developing clinically definite MS.
These results support the notion that there is benefit to early treatment of people with MS or even at risk for developing MS. The relatively short duration of the study (two years) makes it impossible to determine whether such treatment has longer-term benefits on MS symptoms and on the progression of disability.
In an accompanying editorial to the ETOMS paper, Dr. George C. Ebers (University of Oxford, UK) states that, “…Comi and colleagues are continuing to track the patients in the ETOMS study, so more useful information might be obtained during the follow-up.”
-- Research Programs Department