Glatiramer Acetate and Interferon Beta 1a and 1b for Clinically Isolated Syndrome: A Review of Clinical Effectiveness and Guidelines

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating, degenerative disease of the central nervous system characterized by axonal injury and loss. Approximately 77,000 Canadians aged 20 years and older live with MS and almost 75% are women. The majority of new patients are aged 20 to 49 years. A possible precursor of MS is clinically isolated syndrome (CIS) which refers to a single demyelinating event lasting at least 24 hours. As with MS, patients with CIS may present with optic neuritis or symptoms suggestive of a brain stem syndrome, a cerebellar syndrome, or a spinal cord disorder.Disease-modifying therapies (DMTs) such as glatiramer acetate, interferon beta-1a (IFN β- 1a), and IFN β-1b have been used to treat patients with MS and are therefore potential therapies for patients with CIS., Glatiramer acetate is an immunomodulatory agent that is made of alanine, lysine, glutamate, and tyrosine amino acids. β-IFNs are naturally occurring cytokines that facilitate the growth of anti-inflammatory agents. Though DMTs may be useful in managing patients with CIS, their mechanisms of action and safety profiles are not well-understood., Findings from the PreCISe trial – a double-blind, placebo-controlled RCT – suggested that 20 mg of glatiramer acetate administered subcutaneously once a day was superior to placebo in prolonging the time to conversion from CIS to clinically definite MS (CDMS) but its effect on disability was unclear. Based on this evidence, the Canadian Drug Expert Committee (CDEC) recommended in 2009 that glatiramer acetate (Copaxone) not be reimbursed for CIS. A 2012 review by CADTH found that no new evidence regarding the efficacy of glatiramer acetate for treating patients with CIS had been published since the completion of PreCISe. In 2013, based on a systematic review which retrieved one placebo-controlled RCT of IFN β- 1a 44mcg administered subcutaneously, CDEC recommended that it not be reimbursed for CIS. Again, the benefit on disability was unclear.This review aims to summarize and evaluate evidence regarding the clinical effectiveness and safety of glatiramer acetate, IFN β- 1a, and IFN β-1b, in treating patients with CIS. The review also aims to summarize and assess relevant evidence-based guidelines.