Avonex Avonex (Interferon Beta-1a) Provides Long-Term Efficacy in Relapsing Multiple Sclerosis Multiple Sclerosis Drug Avonex (Interferon Beta-1a) As Effective As Betaseron (Interferon Beta-1b) With Fewer Side Effects Avonex (Interferon Beta-1a) Slows Disability Progression In Secondary Progressive Multiple Sclerosis Researchers Report on First Drug Shown to Slow Cognitive Impairment in MS Patients Prefilled Syringe Side effects When you should not use this medicine Warnings

Treats multiple sclerosis.

Avonex (Interferon Beta-1a) Provides Long-Term Efficacy in Relapsing Multiple Sclerosis

By Jill Stein

Special to DG News

DENVER, CO -- April 19, 2002 -- New findings indicate that once weekly intramuscular Avonex (interferon beta-1a) at doses of 30 µg or 60 µg are equally in effective in treating relapsing multiple sclerosis.

The results, presented at the 54^th Annual Meeting of the American Academy of Neurology, (AAN) also indicate that the efficacy of the two doses is sustained after four years of treatment.

The trial's principal investigator was Dr. Ludwig Kappos, with University Hospitals in Basel, Switzerland.

For the study, patients with relapsing multiple sclerosis (MS) who had completed at least three years of treatment as part of the European Interferon Beta-1a Dose-Comparison Study were given the option to continue double-blind treatment with either 30 µg or 60 µg intramuscularly once weekly until the completion of the trial. Of 608 patients who completed the first part of the study, 491 subjects had four-year follow-up and 446 completed four years of treatment and follow-up.

The 30 µg and 60 µg treatment groups were similar with respect to age, gender, race, duration of MS, Expanded Disability Status Scale score, magnetic resonance imaging measures of disease activity, and pre-study exacerbation rates.

Analysis of four-year data was conducted on several end points: cumulative rate of sustained disability progression, extent of change in Expanded Disability Status Scale score, relapse rate, and percentage of relapse-free patients, use of intravenous steroids, and neutralizing antibody (NAB) formation.

Results showed that the two study doses were equally effective for up to four years, and there were no significant differences between doses on any of the clinical end points.

Overall, 52 percent of patients in the 30 µg group were free of disability progression at four-year follow-up compared with 57 percent in the 60 µg group (rate ratio, 0.89; 95 percent confidence interval [CI], 0.72 to 1.11; p = 0.32). The percentage of relapse-free patients was 18 and 19 percent in the two groups, respectively (p=0.85).

The incidence of patients who were NAB formation at any time during the study was 2.3 percent in the 30 µg group and 5.8 percent in the 60 µg group (p=0.011).

Dr. Kappos said that the investigation is the largest long-term study ever conducted in MS without patient re-randomization. He also noted that the results concur with the effects of interferon beta-1a on sustained disability progression observed in the pivotal phase III trial.

The trial was supported by Biogen, Inc.

Multiple Sclerosis Drug Avonex (Interferon Beta-1a) As Effective As Betaseron (Interferon Beta-1b) With Fewer Side Effects

BARI, ITALY -- December 10, 2001 -- The use of interferon beta-1a (Avonex®) for the treatment of relapsing-remitting multiple sclerosis (RRMS) stabilizes the disease by delaying progression of patient disability, according to an independent study presented at the 17th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2001) in September.

The study found that Avonex, when compared to interferon beta-1b (Betaseron® in United States; Betaferon outside the U.S.), might also favorably impact the quality of life of patients with multiple sclerosis (MS).

The study found that both Avonex and Betaseron demonstrated efficacy in reducing relapses associated with RRMS. Avonex dosed once weekly reduced relapses by 65 percent, compared to 59 percent in the Betaseron group dosed every 48 hours.

"This study confirms that treatment with both interferon beta therapies is well tolerated and effective for patients with relapsing-remitting MS," said Professor Maria Trojano, Neurologist in charge of the MS Center, at the Department of Neurological and Psychiatric Sciences, directed by Professor Paolo Livrea, University of Bari, Bari, Italy, and lead investigator of the study. "However, patients treated with interferon beta-1a may have a better compliance rate than patients treated with interferon beta-1b due to the infrequency of adverse events."

Patients treated with Avonex experienced a lower incidence of side effects during treatment initiation. In the first three months of treatment, patients treated with Betaseron experienced more clinical and hematologic side effects compared with Avonex patients.

Even though the incidence of side effects declined during the first year of treatment, patients treated with Betaseron continued to experience more injection-site reactions. Fewer Avonex patients discontinued treatment during the trial than did patients treated with Betaseron (9 percent versus 19 percent).

The population-based surveillance study was conducted to evaluate the efficacy and safety of Avonex and Betaseron in RRMS patients. Relapse rates, Expanded Disability Status Scale (EDSS) scores, adverse events, and study dropouts were evaluated every three months during the two-year study. Of the patients enrolled, 408 patients completed two years of treatment with either Avonex (177 patients) or Betaseron (231 patients). Patients in both treatment groups had significant reduction in relapse rates at all time points compared with baseline. While no differences were shown in mean relapse rates or mean EDSS scores from baseline to year two, patients in the Avonex treated group experienced no significant change in EDSS scores, which measure physical disability, compared to a significant increase over baseline in the Betaseron- treated group.

The study, led by researchers at the University of Bari in Bari, Italy and conducted through a network of 16 specialized MS Centers throughout southern Italy, enrolled 1,033 patients with RRMS. Results also showed that age at treatment onset and the pre-treatment disease duration and relapse rate are all factors influencing the clinical response to treatment. These findings suggest that the earlier patients start on treatment, the better they will respond to therapy.

The most common side effects experienced by enrollees treated with Avonex compared to Betaseron included fever (50 percent vs. 70 percent), depression (6 percent vs. 14 percent), leukopenia (increased risk of infection) (6 percent vs. 22 percent), anemia (reduction in the concentration of red blood cells) (5 percent vs. 18 percent), and thrombocytopenia (reduction in the number of platelets) (1 percent vs. 4 percent).

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 400,000 Americans and about one million individuals worldwide. It is a disease of young adults, mostly women, with onset typically between 20 and 40 years of age. Symptoms of MS may include vision problems, loss of balance, numbness, difficulty walking and paralysis.

The disease is believed to be caused by the destruction of myelin by the immune system. Myelin is the fatty tissue that surrounds and protects central nervous system nerve fibers and facilitates the flow of nerve impulses to and from the brain. The loss of myelin disrupts the conduction of nerve impulses, producing the symptoms of MS.

SOURCE University of Bari
 

Avonex (Interferon Beta-1a) Slows Disability Progression In Secondary
Progressive Multiple Sclerosis



By Jill Stein

Special to DG News


PHILADELPHIA, PA -- May 9, 2001-- New findings indicate that Avonex
(interferon beta-1a) is an effective treatment for secondary
progressive multiple sclerosis (MS).

The Food and Drug Administration (FDA) approved Avonex for the
treatment of relapsing remitting MS.

The data, from a phase III study reported at the 53rd Annual Meeting
of the American Academy of Neurology (AAN), showed that patients with
secondary progressive MS who were treated with Avonex had a 40
percent decrease in the progression of disability compared to
patients who received a placebo.

"Our results are important because they demonstrate that Avonex also
benefits patients at later stages of the disease," said Dr. Jeffrey
A. Cohen, with the Cleveland Clinic Foundation in Cleveland Clinic.

Currently, none of the FDA approved drugs for the treatment of
relapsing remitting MS has been approved for the treatment of the
secondary progressive form of the disease. The present study tested
the efficacy of Avonex for the treatment of the more progressive form
of the disease.

The trial included 426 patients with clinically definite MS, a
secondary progressive course with or without recent relapses, and a
baseline Expanded Disability Status Scale (EDSS) score of 3.5-6.5
inclusive.

Subjects were randomized to treatment with Avonex 60 µg or placebo by
weekly intramuscular injection.

The primary disease end point was disease progression as measured by
the MS Functional Composite Score (MSFC), a measurement of
ambulation, arm movement and cognitive function.

In addition to a decrease in the median disability progression
favoring Avonex, Avonex-treated patients had a 33 percent decrease in
the disease relapse rate.

No benefit was seen on clinical measures driven by ambulation.

Avonex-treated patients also had improvement in eight of 11 Quality
of Life Inventory subscales and experienced a reduction in new or
enlarging T2 hyper-intense cranial magnetic resonance imaging (MRI)
lesions and gadolinium enhancements at months 12 and 24.

The International Multiple Sclerosis Secondary Progressive Avonex
Clinical Trial (IMPACT) was conducted at 42 centers in Europe and
North America.

 

Drug slows onset of MS, study finds

Patients who had early signs of the disease were given Avonex. It costs $10,000 a year, though.

By Shankar Vedantam
INQUIRER STAFF WRITER

Aggressively treating patients with very early signs of multiple sclerosis - well before the crippling nerve disease is usually diagnosed - can delay the onslaught of the disease and mute its damage.

A study, conducted in 50 centers across the United States and Canada, including in Philadelphia, found results so dramatic that researchers stopped the trial midway and called for early drug intervention for all patients at risk for MS.

"This is huge," said Steven Galetta, a professor of neurology at the University of Pennsylvania, one of the centers that studied the impact of early treatment with the drug Interferon beta-1A. "It has profound implications regarding those patients at high risk for MS."

"The earlier you treat MS, the better off you are," he said.

The study is to be published tomorrow in the New England Journal of Medicine.

The study was sponsored by Cambridge, Mass.-based Biogen Inc., a biotechnology firm that sells the drug Avonex, used in the trial. Avonex is commonly used for MS patients but has not been prescribed so early.

Multiple sclerosis affects about 350,000 people in the United States, according to the National Multiple Sclerosis Society. Women are two to three times more likely to be affected than men.

The disease is characterized by symptoms such as blurred or weakened vision, weakness in the fingers and toes, numbness and imbalance. It sometimes progresses to the point where patients are partially paralyzed and wheelchair-dependent.

Scientists have found that symptoms are caused by the destruction of the myelin sheath that covers nerve fibers – akin to the breakdown of the insulation of a telephone wire. This disrupts the transmission of messages within the nervous system and increases the risk of damage to the underlying nerves.

Piecing together a diagnosis of MS from early symptoms can be difficult since they are common to other conditions and sometimes go away. Doctors have so far relied on multiple outbursts - or relapses - and MRI brain scans to make a diagnosis and begin treatment.

The new study and other research indicates that waiting to treat MS may be harmful. Long before physical symptoms develop, the brains of MS patients appear to undergo a steady, stealthy assault.

And for each flare-up in physical symptoms, said doctors, there may be a dozen silent attacks in the brain. These attacks can cause lapses in concentration, memory, attention and judgment as well as physical disabilities.

The study recruited 383 patients who had reported a single outburst of symptoms. An MRI scan established that they were at risk for MS. One half received weekly injections of interferon beta-1A, a drug currently used to treat fully diagnosed MS, while the rest received a dummy injection or placebo.

After three years of follow-up, scientists found that 44 percent fewer patients in the drug group had developed a second outburst of symptoms compared with those in the placebo group. Since the second outburst is the traditional point at which a diagnosis of MS is made, the scientists concluded that their treatment had substantially delayed the disease.

Even more impressive, according to the researchers, treated patients saw 90 percent fewer brain lesions in certain MRI scans, a crucial benefit, given that such damage to the brain is irreversible.

Eventually half the patients in the placebo group went on to develop MS, compared with just over a third in the group that got the drug.

Lawrence Jacobs, professor of neurology at the State University of New York in Buffalo and the lead investigator of the study, said the results boded well for long-term prognosis.

"It's very good to increase the length of time between the first and second relapse and reduce the number of lesions," he said.

Two difficulties can prevent the implementation of the study results: A year's supply of Avonex can cost $10,000, raising questions about access to care. Second, with the inherent difficulty in diagnosis, patients need to take early symptoms seriously and consult a neurologist, Jacobs said.

The most common early signs to watch for, he said, are lost vision in one eye, pain with eye movements, double vision, coordination problems, and an electric shock-like sensation down the spine when the chin is pressed against the chest.

Researchers Report on First Drug Shown to Slow Cognitive Impairment in MS Patients

Portland, Oregon (December 4, 2000)

Treatment with Avonex® (Interferon beta-1a) has Proven Positive Effect on Cognition

A new study published in the Annals of Neurology shows that treatment with interferon beta-1a, or Avonex, has a significant beneficial effect on the cognitive impairment often suffered by people with relapsing multiple sclerosis (MS). Researchers report that

patients treated with Avonex, an MS therapy already proven to reduce MS relapses and to slow the progression of the disease, performed significantly better than placebo-treated patients on measures of cognitive functioning most commonly disrupted by MS. In fact, patients treated with Avonex had a 47 percent reduction in the risk of experiencing cognitive deterioration versus patients who were treated with placebo.

According to Oregon Health Sciences University, about half of all people with multiple sclerosis experience some form of cognitive dysfunction, such as memory loss, slowed information processing and difficulty in problem solving. Cognitive dysfunction, not physical disability, is cited as the most common reason people with MS leave the work force. More than 400,000 people in the U.S. and over one million worldwide have multiple sclerosis. "The loss of cognitive abilities is a common, yet under-recognized, problem of MS, a disease best known for its debilitating effect on one's physical abilities, not mental abilities," said study co-author Dennis N. Bourdette, M.D., Director, Multiple Sclerosis Center of Oregon, Oregon Health Sciences University. "This study shows that proactive treatment with Avonex has a significant overall positive effect on cognitive functioning in patients with relapsing multiple sclerosis."

Researchers led by Jill Fischer, Ph.D., a neuropsychologist at the Cleveland Clinic's Mellen Center for MS Treatment and Research at the time the research was conducted, administered a comprehensive battery of neuropsychological tests to a subset of 166 persons with MS enrolled in the original double-blind, placebo-controlled trial of Avonex in relapsing MS.

"According to the study, patients treated with Avonex were almost 50% less likely to worsen neuropsychologically compared to those who did not receive Avonex therapy," Bourdette said. "It is clear that cognitive dysfunction should be considered when making decisions regarding disease-modifying therapy in MS."

The positive effects of Avonex were most pronounced on cognitive domains most frequently affected by MS. These areas include information processing (the ability to focus, sustain and shift attention particularly when information is presented rapidly) and learning and memory tasks (ability to learn new information and remember it later). There was also a beneficial trend in other cognitive domains that are impaired moderately often in MS, including higher-level executive functions and visuospatial abilities. "This is the first multi-center clinical trial in MS to prospectively assess neuropsychological outcomes across a wide range of cognitive functions,"

said Fischer. "We believe that treatment with Avonex exerts its neuropsychological effects via both short- term mechanisms, by inhibiting inflammation, and longer term mechanisms by slowing or preventing further central nervous system tissues damage. By modifying the disease process in MS, we may be able to preserve important cognitive functions that can directly affect a person's ability to carry out those daily activities that are most important to him or her."

According to Dr. Bourdette, this extensive and irreversible cognitive impairment is most likely attributable to cerebral plaque accumulation and brain atrophy. Avonex has already been clinically proven to favorably affect brain atrophy and cerebral lesions. Previous studies with other MS treatments failed to show the same positive effect on cognition.

"MS-related cognitive dysfunction can have a devastating impact on individuals with MS and their families, affecting employment, social functioning and quality of life," said Stephen Reingold, Ph.D., Vice President Research, of the National Multiple Sclerosis Society. "This new report is important because it indicates that treatment with this disease-modifying agent, Avonex, can have significant impact on this important symptomatic problem that affects many with MS."