Advances in the treatment of relapsing–remitting multiple sclerosis: the role of pegylated interferon β-1a

Abstract

Multiple sclerosis (MS) is a progressive, neurodegenerative disease with unpredictable phases of relapse and remission. The cause of MS is unknown, but the pathology is characterized by infiltration of auto-reactive immune cells into the central nervous system (CNS) resulting in widespread neuroinflammation and neurodegeneration. Immunomodulatory-based therapies emerged in the 1990s and have been a cornerstone of disease management ever since. Interferon β (IFNβ) was the first biologic approved after demonstrating decreased relapse rates, disease activity and progression of disability in clinical trials. However, frequent dosing schedules have limited patient acceptance for long-term therapy. Pegylation, the process by which molecules of polyethylene glycol are covalently linked to a compound, has been utilized to increase the half-life of IFNβ and decrease the frequency of administration required. To date, there has been one clinical trial evaluating the efficacy of pegylated IFN. The purpose of this article is to provide an overview of the role of IFN in the treatment of MS and evaluate the available evidence for pegylated IFN therapy in MS.

Illuminating an Invisible Epidemic: A Systemic Review of the Clinical and Economic Benefits of Early Diagnosis and Treatment in Inflammatory Disease and Related Syndromes

“…The pathology of MS is characterized by infiltration of auto-reactive T cells, B cells, and other immune mediators into the CNS, culminating in widespread neuroinflammation and neurodegeneration [30]. Neuroinflammation results in patients developing symptoms that include sensory disturbances, visual impairments, muscle weakness, difficulty walking, and problems with coordination [31].…”

Current immunotherapies for multiple sclerosis and neuromyelitis optica spectrum disorders: the similarities and differences

“…It causes fewer adverse reactions, so it is a safe and generally well tolerated drug for NMOSD [169] . The efficacy of rituximab is better than that of azathioprine regulates T-, B-, natural killer, and dendritic cells; blocks leukocyte migration to the central nervous system [99][100][101] RRMS [87][88][89][90][91][92][93] , SPMS [94][95][96] , PPMS [97,98] [102][103][104] RRMS [105][106][107][108][109] , PPMS [110] Mitoxantrone Novantrone, 2000 12 mg/m 2 , once every 3 months, iv…”

<p>Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy</p>

“…2 Since these initial theories were proposed, it has been demonstrated that IFNβ has pleiotropic effects on the peripheral immune system including reducing pathogenic Th1 and Th17 cells and increasing Tregs that produce IL-10 via the JAK-STAT signaling pathway. [3][4][5] Additionally, IFNβ has been shown to reduce CD27+ memory B cells and increase IL-10 producing transitional B cells, which is thought to be beneficial on disease activity. 3 Finally, IFNβ may downregulate adhesion molecules suppressing the ability of pro-inflammatory cells to enter the CNS.…”

“…3 Finally, IFNβ may downregulate adhesion molecules suppressing the ability of pro-inflammatory cells to enter the CNS. 5 There are currently multiple formulations of IFNβ that are approved for use in clinically isolated syndrome, relapsing remitting MS (RRMS), and secondary progressive MS (SPMS) with relapses. These include IFNβ-1b (Betaseron ® and Extavia ® ) that are administered subcutaneously every other day at a dose of 250μg, IFNβ-1a that is administered intramuscularly once a week (Avonex ® ) at a dose of 30μg, IFNβ-1a (Rebif®) that is administered subcutaneously three times weekly at a dose of 22 or 44μg, and pegylated IFNβ-1a (Plegridy®) that is administered subcutaneously every 2 weeks at a dose of 125μg.…”

“…These include IFNβ-1b (Betaseron ® and Extavia ® ) that are administered subcutaneously every other day at a dose of 250μg, IFNβ-1a that is administered intramuscularly once a week (Avonex ® ) at a dose of 30μg, IFNβ-1a (Rebif®) that is administered subcutaneously three times weekly at a dose of 22 or 44μg, and pegylated IFNβ-1a (Plegridy®) that is administered subcutaneously every 2 weeks at a dose of 125μg. 5 Interferons effect on disease activity in MS is multifactorial and not fully understood. Since the pivotal approval of IFNβ, the therapeutic landscape has rapidly and continuously expanded with 18 FDA-approved DMTs for MS to date (Figure 1).…”