2006Expert Review of Clinical ImmunologyRequires access

Interferon-β1a: a once-weekly immunomodulatory treatment for patients with multiple sclerosis

R. Philip Kinkel

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Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. The most common form of MS at onset, relapsing-remitting disease, is defined not by pathological features but by unpredictable periods of acute or subacute neurological worsening, followed by gradual improvement over weeks to months, often with residual neurological deficits. Evidence from serial magnetic resonance imaging studies in relapsing-remitting disease reveals significant inflammation, demyelination and axonal loss occurring both during and between relapses. Disease-modifying agents, such as interferon (IFN)-beta(1a), reduce the frequency of relapse by 30% in well established relapsing patients, reduce the risk of a second attack by 50% in high-risk patients, following a first attack, and reduce the number and volume of magnetic resonance imaging lesions. Intramuscular IFN-beta(1a) is effective in delaying disability progression and brain atrophy. The relationship between response to therapy and pathological subtype of MS is unknown. This review summarizes key findings of Phase III clinical trials, extension studies and postmarketing trials, demonstrating the efficacy and safety of intramuscular IFN-beta(1a). Results demonstrating the negative impact of anti-IFN-beta neutralizing antibodies on clinical efficacy are also addressed. Finally, expert commentary regarding the treatment of MS with IFN-beta therapy and future strategies to augment intramuscular IFN-beta(1a) efficacy by combination treatment with other agents is presented.

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What this paper is about

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. The most common form of MS at onset, relapsing-remitting disease, is defined not by pathological features but by unpredictable periods of acute or subacute neurological worsening, followed by gradual improvement over weeks to months, often with residual neurological deficits. Evidence from serial magnetic resonance imaging studies in relapsing-remitting disease reveals significant inflammation, demyelination and axonal loss occurring both during and between relapses. Disease-modifying agents, such as interferon (IFN)-beta(1a), reduce the frequency of relapse by 30% in well established relapsing patients, reduce the risk of a second attack by 50% in high-risk patients, following a first attack, and reduce the number and volume of magnetic resonance imaging lesions. Intramuscular IFN-beta(1a) is effective in delaying disability progression and brain atrophy. The relationship between response to therapy and pathological subtype of MS is unknown. This review summarizes key findings of Phase III clinical trials, extension studies and postmarketing trials, demonstrating the efficacy and safety of intramuscular IFN-beta(1a). Results demonstrating the negative impact of anti-IFN-beta neutralizing antibodies on clinical efficacy are also addressed. Finally, expert commentary regarding the treatment of MS with IFN-beta therapy and future strategies to augment intramuscular IFN-beta(1a) efficacy by combination treatment with other agents is presented.

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Available abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. The most common form of MS at onset, relapsing-remitting disease, is defined not by pathological features but by unpredictable periods of acute or subacute neurological worsening, followed by gradual improvement over weeks to months, often with residual neurological deficits. Evidence from serial magnetic resonance imaging studies in relapsing-remitting disease reveals significant inflammation, demyelination and axonal loss occurring both during and between relapses. Disease-modifying agents, such as interferon (IFN)-beta(1a), reduce the frequency of relapse by 30% in well established relapsing patients, reduce the risk of a second attack by 50% in high-risk patients, following a first attack, and reduce the number and volume of magnetic resonance imaging lesions. Intramuscular IFN-beta(1a) is effective in delaying disability progression and brain atrophy. The relationship between response to therapy and pathological subtype of MS is unknown. This review summarizes key findings of Phase III clinical trials, extension studies and postmarketing trials, demonstrating the efficacy and safety of intramuscular IFN-beta(1a). Results demonstrating the negative impact of anti-IFN-beta neutralizing antibodies on clinical efficacy are also addressed. Finally, expert commentary regarding the treatment of MS with IFN-beta therapy and future strategies to augment intramuscular IFN-beta(1a) efficacy by combination treatment with other agents is presented.

Key concepts: Medicine, Multiple sclerosis, Magnetic resonance imaging, Clinical trial, Atrophy, Disease, Internal medicine, Glatiramer acetate

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