Critical Papers in Multiple Sclerosis: From Evidence to Practice for Managed Care Pharmacists

Emerging Options for MS Therapy: Efficacy and Safety

Supported by an educational grant from Biogen IDEC.

OVERVIEW
Multiple sclerosis (MS) is a chronic, disabling autoimmune disease that typically occurs for the first time in young adults.1 Most patients experience 2 distinct stages of MS: an early phase that is characterized by episodes of central nervous system (CNS) inflammation, acute symptom exacerbations, and symptom-free remissions; and a later stage of neurodegeneration, fewer acute exacerbations, and the gradual accumulation of permanent disability.2 Over the last 2 decades, the introduction of several disease-modifying drugs has transformed the treatment of MS. First-line disease-modifying agents, including interferon ß-1a, interferon ß-1b, and glatiramer acetate (GA), significantly decrease magnetic resonance imaging evidence of disease activity, reduce the number of relapses, and delay the transition to definite MS when treatment is initiated at the earliest signs of MS.3 The long-term safety and tolerability of interferon ß and GA have been demonstrated over many years of careful study in prospective, clinical trials, and most patients are able to self-administer therapy for extended periods of time. However, there are important limitations with currently available first-line agents. Many patients continue to experience relapses despite first-line therapy, although at a lower rate than before treatment. The first-line agents act primarily on CNS inflammation, and are thought to have less effect on neurodegeneration and the gradual progression of disability.4 In addition, patients are generally required to perform regular self injections, which may be a barrier to long-term adherence. Newer treatment options are being explored for MS, and many have produced significant improvement in MS symptoms in clinical studies. In some cases, newer treatments have improved outcomes in patients who did not respond adequately to first-line therapies. However, these agents act by different mechanisms than the conventional first-line treatments, they cause a variety of potentially serious adverse events that have been unusual in MS care until now, and the long-term efficacy and safety of newer treatments will require careful study to understand how they should be integrated into MS care.5

This University of Tennessee Advanced Studies in Pharmacy journal club module provides managed care pharmacists with brief, focused reviews of recent publications and CMSC 2010 Annual Meeting abstracts that have examined the efficacy and safety of new treatment approaches to MS. The studies selected for this journal club describe the use of fingolimod, the first oral disease-modifying agent; cladribine, a second oral agent that is being investigated for MS treatment; rituximab, a monoclonal antibody that reduces B lymphocyte activity; ibudilast, an immunomodulator that is used in Asia; and alemtuzumab, a monoclonal antibody that depletes T and B lymphocytes. These brief reviews will provide an overview of some of the central issues in the identification of new options for MS treatment, including efficacy, safety, economic implications, and the potential place of these new agents in MS care.

References
1. Mangas A, Coveñas R, Geffard M. New drug therapies for multiple sclerosis. Curr Opin Neurol. 2010;23:287-292.
2. Rudick RA. Evolving concepts in the pathogenesis of multiple sclerosis and their therapeutic implications. J Neuroophthalmol. 2001;21:279-283.
3. Ryan M, Deno S, Zwibel HL. Review of the clinical debate regarding interventions for multiple sclerosis. J Manag Care Pharm. 2009;15(suppl S-b):S1-S17.
4. Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology. 2008;71:136-144.
5. Spain RI, Cameron MH, Bourdette D. Recent developments in multiple sclerosis therapeutics. BMC Med. 2009;7:74.

GOAL
To provide managed care pharmacists with up-to-date information on emerging options for the treatment of patients with MS.

INTENDED AUDIENCE

This activity is designed for managed care pharmacists. No prerequisites required.

LEARNING OBJECTIVE

The University of Tennessee College of Pharmacy takes responsibility for the content, quality, and scientific integrity of this CPE activity. Upon the conclusion of this activity, the participant should be able to:

  • DISCUSS the potential efficacy of emerging immunotherapies based on available data in comparison to currently available disease-modifying drugs for reducing disability and relapse rate in MS.

CPE INFORMATION

Accreditation Statement
The University of Tennessee College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education to provide continuing education for pharmacists.

Credit Designation Statement
The University of Tennessee College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Successful completion of this knowledge-based educational activity will provide 1.5 contact hours credit (0.15 CEUs). A statement of CPE credit will be available online immediately following successful completion of the activity. Successful completion includes taking the pre-test, attending the session, and completing the post-test and educational activity evaluation. ACPE Program #0064-0000-10-219-H01-P.

After reviewing this online activity, participants may receive credit by completing the CPE test, evaluation, and receiving a score of 70% or higher.

The estimated time to complete this activity: 1.5 hours.

Release date: October 31, 2010. Expiration date: October 31, 2011.

Fee: There is no fee for this educational activity.

STEERING COMMITTEE

Full Disclosure Policy Affecting CME Activities
As an accredited provider by the Accreditation Council for Pharmacy Education (ACPE), it is the policy of The University of Tennessee College of Pharmacy to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Steering Committee reported the following:

Jacci Bainbridge, PharmD (Chair)
Associate Professor
Department of Clinical Pharmacy
University of Colorado at Denver
Health Sciences Center
Denver, Colorado
Dr Bainbridge reports receiving grants/research support from the National Institutes of Health; and serving on advisory boards for Bayer and TEVA Pharmaceuticals.

Melody Ryan, PharmD, MPH, BCPS, CGP
Associate Professor
Department of Pharmacy Practice and Science
University of Kentucky College of Pharmacy
Department of Neurology
University of Kentucky College of Medicine
Lexington, Kentucky
Dr Ryan reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Sheldon J. Rich, RPh, PhD
President – SJR Associates, LLC
Clinical Assistant Professor –  University of Michigan
Adjunct Assistant Professor – Wayne State University
Palm Beach Gardens, Florida
Dr Rich reports serving as a consultant for Serono and TEVA Neuroscience.

Off-Label Product Discussion
In accordance with ACPE Criteria for Quality, the audience is advised that authors in this CPE activity may include reference(s) to unlabeled, unapproved, or investigational uses of therapeutic agents or biomedical devices. The authors will inform the reader of when they discuss or reference an unapproved, unlabeled, or investigational use of therapeutic agent or biomedical device.

DISCLAIMER
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The University of Tennessee College of Pharmacy name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

GRIEVANCE POLICY
A participant, sponsor, faculty member, or other individual wanting to file a grievance with respect to any aspect of an educational activity sponsored or cosponsored by The University of Tennessee College of Pharmacy may contact the Associate Dean for Continuing Education in writing. The grievance will be reviewed and a response will be returned within 45 days of receiving the written statement. If not satisfied, an appeal to the Dean of the College of Pharmacy can be made for a second level review.

JOURNAL CLUBS
Please complete the pre-test, read the following journal clubs, and complete the post-test and evaluation to receive CPE credit for this activity.

Pre-Test

Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402-415.

Naismith RT, Piccio L, Lyons JA, et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology. 2010;74:1860-1867.

Barkhof F, Hulst HE, Drulovic J, et al. Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology. 2010;74:1033-1040.

Consortium of Multiple Sclerosis Centers (CMSC) 2010 Annual Meeting Summaries

  • [S48] Analysis of clinical and radiological disease activity-free status in patients with relapsing–remitting multiple sclerosis (RRMS) treated with cladribine tablets, in the double-blind, 96-week CLARITY study
  • [S31] Oral fingolimod (FTY720) vs placebo in relapsing-remitting multiple sclerosis (RRMS): 2-year efficacy results of the phase III FREEDOMS trial
  • [S1 36] Durable Efficacy of Alemtuzumab Treatment: Clinical Efficacy at Four Years

Post-Test

Step 1. Pre-Test

 
Step 2. Journal Clubs

 
Step 3. Post-Test

 
     
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