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.¹ Approximately 77,000 Canadians aged 20 years and older live with MS and almost 75% are women.² 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.³ 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.⁴ 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.^5,6 Glatiramer acetate is an immunomodulatory agent that is made of alanine, lysine, glutamate, and tyrosine amino acids.⁷ β-IFNs are naturally occurring cytokines that facilitate the growth of anti-inflammatory agents.⁸ Though DMTs may be useful in managing patients with CIS, their mechanisms of action and safety profiles are not well-understood.^6,9 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.¹⁰ Based on this evidence, the Canadian Drug Expert Committee (CDEC) recommended in 2009 that glatiramer acetate (Copaxone) not be reimbursed for CIS.¹¹ 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.¹⁰ 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.¹² 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.