Immunomodulatory medicines for multiple sclerosis: Progress and prospects

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Current therapies are mainly biological agents (b-interferons, a 4-amino acid peptide, and a monoclonal antibody to a cell adhesion molecule on the blood CNS barrier) that either attenuate the inflammatory response or block the movement of immune cells into the CNS. The market landscape for MS drugs is set to change substantially in the near future with the market leaders coming off patent, which gives permission for the emergence of biosimilars. In addition, new small-molecule immunomodulatory drugs are beginning to enter the market (Gilenya is the first to gain widespread approval), along with a number of immunomodulatory monoclonal antibodies. Both existing and emerging immunomodulatory medicines for MS are reviewed and their impact on the expression and progression of MS (in all its forms) considered, along with the rapidly changing landscape of MS pharmacotherapy. Drug Dev Res 72:664-673,

New and emerging immune‐targeted drugs for the treatment of multiple sclerosis

“…The first IFNβ drug gained regulatory approval in 1993 and glatiramer acetate in 1997 and have dominated the MS market ever since . However, a number of factors are now changing this situation.…”

Pharmacotherapeuetic Options for the Treatment of Multiple Sclerosis

“…BCNSB disruption permits the movement of more leukocytes into the CNS parenchyma where they probably contribute to the process of neurodegeneration. 2,53,54…”

“…IFNβ-1a (but not IFNβ-1b) is glycosylated with a carbohydrate very similar to that found in human IFNβ and IFNβ-1b (but not IFNβ-1a) has an amino acid substitution at position 17 (serine replacing cysteine), which reduces the probability of erroneous disulfide bond formation. 2 Table 3 describes trials that directly compared one IFNβ drug with another in studies of people with rrMS lasting from 16 to 24 months.…”

“…It constitutes the most common, non-traumatic, disabling neurological disease of young adults, affecting approximately 2.1 million people worldwide. 1–3 The disease is associated with a substantial economic burden, which is attributable to the direct medical costs associated with health along with disability-related resource utilization and indirect costs relating to reduced productivity; there are also indirect costs associated with reduced health-related quality of life. 4 The clinical features of MS are heterogeneous, with its severity ranging from benign to malignant.…”

“…Symptoms include changes in motor function (particularly walking, manual dexterity, and bladder control), sense perception and mental function (particularly affect and cognition). 1–3 Fatigue is a further symptom, which is commonly reported and often initiated by heat. 5…”