Choosing the Best Treatment for Multiple Sclerosis: Comparative Effectiveness, Safety, and Other Factors Involved in Disease-Modifying Therapy Choice

Published Online: November 30, 2013
Laura E. Happe, PharmD, MPH
Comparative effectiveness research (CER) has emerged as a priority for outlining the advantages and disadvantages of disease-modifying therapies (DMTs) for multiple sclerosis (MS). CER can provide physicians with valuable information to assist them in selecting the most appropriate therapeutics for their patients with MS. For payers, data from CER could inform decisions regarding the level of coverage for current and developing MS therapeutics, and drive the use of the most effective treatments for patients with MS. The base of CER data for DMTs has been expanding, and findings from a number of CER studies for currently available DMTs have been published, while further CER studies are planned to evaluate currently available and new DMTs or DMTs in development. While CER can be used to guide DMT selection for physicians and payers, the safety and tolerability of these treatments must be considered as well. Other emerging factors (eg, biomarkers and patient-specific factors) may also serve as important determinants of DMT choice in the future.

(Am J Manag Care. 2013;19:S332-S342)
Clinical and coverage-related decisions in the multiple sclerosis (MS) therapeutic category are growing increasingly complex. Comparative effectiveness research (CER) can aid decision makers in navigating these multifaceted issues. The Institute of Medicine (IOM) defines CER as “the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care.”1 This type of information helps physicians and payers alike in evaluating the advantages and disadvantages of one product relative to other available treatments.2

Multiple factors contribute to the increasing complexity of decision making in the MS category, including the advent of novel MS treatments, increasing costs of therapy, and a lack of up-to-date clinical practice guidelines. In a category historically dominated by injectable therapies, approval of the first oral agents (fingolimod in 2010, teriflunomide in 2012, and dimethyl fumarate in 2013) represents a landmark advancement. In addition to these agents, other oral disease-modifying therapies (DMTs) and monoclonal antibodies are currently in phase 3 development or are awaiting US Food and Drug Administration approval.3,4

These advances in MS therapies come at a price. A study of 361 commercially insured patients with MS showed an 8.2% compounded annual growth rate in per patient per year costs since 2006.5 The authors attribute this rise in costs to drug price inflation, citing an increase in member cost share per 30-day supply from $48 in 2006 to $114 in 2010. This increasing member cost share can be detrimental to the fragile population of patients with MS. In addition to the debilitating effects of the disease, persons newly diagnosed with MS are 3.5 times more likely to be hospitalized and twice as likely to go to the emergency department compared with their non-MS counterparts.6 Increased utilization of medical resources is reflected in the total medical costs incurred by MS patients, which can be nearly 5 times greater than those of healthy individuals. For newly diagnosed MS patients, one-fourth of these incremental costs have been attributed to drug prices.6

As a consequence of new product approvals and escalating drug costs, health plan decision makers are viewing the MS category with increased scrutiny. Jeremy Schaefer, PharmD, MBA, director benefit manager, stated that “Opportunities exist for payers to manage the MS categories and control costs. Preferring select agents on formulary, developing utilization management programs to promote patient safety, and encouraging use of preferred agents and specialty pharmacies all provide opportunities to optimize clinical and service outcomes at the lowest cost.”5 Payers are definitively operationalizing the management of this category. A survey of 93 health plans covering more than 115 million lives revealed that 81% to 86% of plans apply prior authorizations to MS agents and 65% have preferred agents.7 Furthermore, consensus statements from a panel of US managed care pharmacists and physicians have been published in order to aid health plan decision makers in managing this class.8 These statements recommend prior authorizations and preferred agents as viable strategies to appropriately manage the MS category. The article highlighted the lack of comprehensive, up-to-date US-based treatment guidelines as a distinct gap in evidencebased information available to payers to support decision making. Specifically, the most recent MS clinical treatment guidelines from the American Academy of Neurology were published in 2002 (and reaffirmed in 2008) and do not address several of the most recent drug approvals.9 In the absence of definitive guidance from physician associations, health plan decision makers must conduct their own assessments of the available literature and data to inform policies.

Because CER evaluates products in relation to one another, it can help payers determine whether a treatment should be elevated to first-line status, be assigned to a given copayment tier, or require a prior authorization for use.2 MS is on the list of the top 100 initial priority CER topics published by the IOM and funded under the American Recovery and Reinvestment Act.1 Although the full benefits of the prioritization of MS are yet to be realized, there is a growing body of CER on MS therapeutics. This article provides an overview of the available and emerging CER for MS.

Comparative Effectiveness and Relative Safety of MS Therapeutics

Relative Effectiveness Outcomes of Current DMTs

The Drug Effectiveness Review Project (DERP) published a drug class review of the comparative effectiveness of DMTs for MS in 2010, and provided an addendum for fingolimod in 2011.10,11 Five studies that evaluated the comparative effectiveness of interferon beta-1a (intramuscular [IM] or subcutaneous [SC] injection) or interferon beta-1b SC were identified in the 2010 drug class review of DMTs in relapsingremitting MS (RRMS).11 Given the existence of this body of work and, in contrast, the lack of comparative effectiveness data on primary progressive or secondary progressive MS, this review will focus on RRMS. The CER studies for current DMTs are summarized in Table 1.12-30

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