Intramuscular interferon beta-1a and evolving treatment options and outcomes measurement for MS: considerations for managed care.

The treatment options for multiple sclerosis are rapidly changing. With the increasing number of products available to treat this disease, treatment decisions are becoming more complex. Over the years, diagnosis and assessment of treatment efficacy in multiple sclerosis have evolved, but the primary endpoints used to evaluate patients have remained relatively consistent. Relapse rates, magnetic resonance imaging parameters, and disability progression are all key considerations when assessing efficacy for multiple sclerosis treatments. As selection of therapy becomes increasingly complex for both patients and physicians, risk-benefit considerations that incorporate long-term efficacy and safety on an individualized basis will be of greater importance. The information provided in this article will help to elucidate these considerations. J Manag Care Pharm. 2013;19(1-a):S4-S15 Copyright © 2013, Academy of Managed Care Pharmacy. All rights reserved. • Multiple sclerosis (MS) is a chronic, immune-mediated neurologic disease that is associated with progressive disability and diminished quality of life by interfering with a person’s ability to work, pursue leisure activities, and conduct typical life activities. • Several approved disease-modifying therapies (DMTs) are available to treat MS. These DMTs have demonstrated efficacy in key traditional MS outcome measures, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. • This article provides an overview of the key traditional outcomes assessed in MS studies and critically evaluates phase 3 and longterm follow-up outcomes data for intramuscular interferon beta1a (IM IFNβ-1a), one of the frequently prescribed treatments for patients with MS. • IM IFNβ-1a administered once weekly has demonstrated efficacy in reducing relapse rates, disability progression, and disease activity visible on MRI in multiple MS studies. • IM IFNβ-1a has been an effective first-line treatment option for patients with MS for more than 15 years. Its efficacy and safety profiles have been well established in the post-marketing setting, and no new safety considerations have emerged. The adverse reactions most commonly reported in patients associated with the use of IM IFNβ-1a are flu-like symptoms occurring within hours to days following an injection. Summary Points Presented in this Article MS will result in significant changes in treatment. Fingolimod is the most recently approved DMT for treatment of relapsing forms of MS, and several other drugs are currently in late-stage development. The pivotal studies for these latest therapies, which include laquinimod,27,28 teriflunomide,29-31 dimethyl fumarate (BG-12),32,33 alemtuzumab,34 and PEGylated interferon beta-1a,35 have primary endpoints (relapse rates, disability progression, MRI activity) similar to those used in the registration trials of currently approved DMTs. Because traditional measures of efficacy in MS do not capture other important aspects of the disease, additional measures, including the Multiple Sclerosis Functional Composite (MSFC), cognition, and quality of life (QoL), as well as newer imaging techniques, such as brain atrophy and magnetization transfer, are often included as endpoints in more recent clinical trials.24,27,35,36 The objective of this article is to provide an overview of the key traditional outcomes assessed in MS studies and to summarize and critically evaluate the 2 published phase 3 studies and respective long-term follow-up outcomes data for IM IFNβ-1a, one of the more frequently prescribed treatments for patients with MS. This review provides an overview of traditional MS outcomes and is not a systematic review of all studies of the drug. The studies selected for this review examined patients who were naive to treatment with IFNβ. Evidence supporting the use of relapses, disability progression, and MRI activity in clinical trials will be summarized. A brief overview of the key clinical trials and a long-term follow-up study for IM IFNβ-1a are provided, and the primary and secondary efficacy outcomes from these studies are described. Finally, important considerations for clinical trials in MS are reviewed. ■■ Traditional MS Outcome Measures Expanded Disability Status Scale Measures of disability have often been used to assess efficacy in the clinical trials of the treatments that have received approval of the U.S. Food and Drug Administration (FDA) for MS. Measuring disability is clinically relevant because it is an evaluation of the long-term progressive course of the disease. The Kurtzke Expanded Disability Status Scale (EDSS) is the most commonly used measure of neurologic impairment in MS clinical trials.37-39 The EDSS scale ranges from 0.0 (indicating no clinical effects) to 10.0 (indicating death due to MS) in 0.5-unit increments. EDSS scores are based on the sum of 8 functional systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral function.37 Functional system scores have a greater bearing on total scores of < 4.5, whereas higher scores are influenced more by the patient’s ambulation status. The EDSS scale is nonlinear. A 1.0-point change in EDSS at the low end of the scale is often Several disease-modifying therapies (DMTs) are currently approved to treat multiple sclerosis (MS), with proven efficacy in reducing relapse rates, disability progression, and disease activity visible on magnetic resonance imaging (MRI).1,2 Positive outcomes for approved DMTs (subcutaneous [SC] interferon beta-1b [IFNβ-1b],3-7 intramuscular [IM] IFNβ-1a,8-11 glatiramer acetate,12-16 SC IFNβ-1a,17-21 natalizumab,22,23 fingolimod,24,25 and mitoxantrone26) have been demonstrated in patients with MS for many of these endpoints. Over the next few years, the introduction of new agents to treat