2009 Update on the Science of Multiple Sclerosis: Managed Care Pharmacist Perspectives
J. Jacquelyn Bainbridge, PharmD, FCCP*
Achronic, progressive autoimmune disorder of the central nervous system (CNS), multiple sclerosis (MS) is estimated to affect approximately 400 000 Americans and 2.5 million people worldwide. Most patients are diagnosed with MS between the ages of 20 and 50, and those who are more likely to be afflicted include women and individuals of northern European descent.1 Both the symptoms and course of MS appear to be somewhat unpredictable, with some individuals experiencing mild illness, with few relapses that produce effects such as fatigue, numbness, and stiffness. Other patients suffer from more progressive disease and experience increasingly severe symptoms (eg, slurred speech, tremors, difficulty walking, and cognitive dysfunction) and permanent disability.
Researchers examining the pathophysiology of this disease have made several observations that underscore the need for early treatment. Essentially, they have determined that disease progression occurs in the absence of clinical relapses, as evidenced by magnetic resonance imaging (MRI) studies that have demonstrated ongoing brain lesion development and atrophy among individuals in clinical remission. Even early relapses that appear relatively benign may have permanent neurologic consequences. Researchers have also found that beyond the deregulated inflammatory cascade that causes demyelination, evidence of progressive neurodegeneration exists. This pathologic phenomenon, which leads to a loss of brain volume and ultimately to cognitive dysfunction, is known to occur early in the disease, is independent of axonal loss, and may continue well after the inflammatory process is suppressed. As such, the National MS Society has recommended, in their disease management consensus statement, that disease-modifying therapy, with either an interferon or glatiramer acetate, be made available early in the disease process to appropriate candidates, and that mitoxantrone and natalizumab be available for patients with aggressive relapsing disease and for those not responding to other treatments.2
The aforementioned disease-modifying drugs have increasingly been shown (in relapsing disease) to have positive long-term outcomes including a reduction in the frequency of relapses, reduction of brain lesion development (as shown in MRI studies), and possible reduction of disability progression. As a result, clinicians and researchers have concluded that these agents are likely to reduce future disease activity and improve patient quality of life, but that treatment must be sustained for years because discontinuation may result in progression of disease activity.
As with most chronic conditions, MS presents many challenges that are inherent to managing patients requiring lifelong treatment and follow-up. With results of a longitudinal study indicating that 43% of patients are not being treated with a disease-modifying drug,1 one of the main issues in this disease is making treatment available to all patients and making certain that patients remain on treatment. Indeed, one of the greatest challenges to optimal patient care is ensuring patient adherence to treatment. The 2 reasons given most often for treatment discontinuation are adverse effects and lack of efficacy. Adverse effects can be anticipated and managed through well-established protocols that can reduce needless discontinuations when patients experience common problems. Perceived lack of efficacy can be addressed by providing patients with enough education to develop reasonable expectations for treatment and long-term prognosis.
Managed care pharmacists can play an essential role in MS by educating patients and clinicians about current treatment approaches, as well as by monitoring therapeutic efficacy and potential adverse effects. In addition, managed care pharmacists can become involved in developing protocols that may be used to address a myriad of issues (ie, breakthrough disease, appropriate diagnostic follow-up, and cost of medication) that arise in the comprehensive care of patients with MS. This issue of University of Tennessee Advanced Studies in Pharmacy is based on a Webcast series held in May through June 2009, which was intended to offer a thorough and timely update on the pathophysiology and treatment of MS, as well as a practical, managed care perspective on the care of patients with MS.
In a discussion on the pathophysiology of MS, Jeffrey L. Bennett, MD, PhD, explores the immunopathologic origins of the disease and how the immunologic cascade of cellular events relates to disease progression and compensation within the CNS. Dr Bennett reviews the cellular characteristics of plaques and the different patterns of demyelination, and also examines the current rationale for the increasingly aggressive therapeutic approach in MS.
Melody Ryan, PharmD, MPH, BCPS, CGP, focuses on comparative efficacy and adverse-effect profiles of currently available disease-modifying therapies. She examines methods of alleviating common adverse effects (eg, injection site reactions and flu-like symptoms) and offers a discussion on factors implicated in nonadherence to treatment.
Ellen Whipple Guthrie, PharmD, reveals new research regarding MS pathology, specifically that which relates to neurodegeneration and its relation to the inflammatory process. Dr Guthrie highlights the current challenges related to assessing neurodegeneration, and reviews the available data on current and emerging treatments that target neuroprotection.
Sheldon J. Rich, RPh, PhD, offers an extensive discussion of the practical treatment considerations in MS, including monitoring of disease progression and treatment adherence, and management of progression-related symptoms and breakthrough disease. He emphasizes the importance of ensuring treatment adherence because 17% to 40% of patients who are prescribed a disease-modifying drug will discontinue treatment within 1 year of initiation. He also includes examples of treatment algorithms that can be used to help guide clinicians in stratifying patients, making evidence-based therapeutic decisions, and optimizing patient outcomes. At the conclusion of his discussion, Dr Rich presents a case study, intended to illustrate how pharmacists can help patients choose among the different disease-modifying therapies.
Finally, each Webcast included a question and answer session reprising major points and additional insights from the faculty. The monograph concludes with highlights from these sessions.
1. Just the facts 2007-2008. National Multiple Sclerosis Society Web site. Available at: www.nationalmssociety.org/ download.aspx?id=22. Accessed June 26, 2009.
2. Disease management consensus statement. The National Clinical Advisory Board of the National Multiple Sclerosis Society. Available at: www.nationalmssociety.org/download.aspx?id=8. Accessed June 26, 2009.
*Professor, Department of Clinical Pharmacy/ Department of Neurology, University of Colorado Denver, Aurora, Colorado.
Address correspondence to: Jacquelyn Bainbridge, PharmD, FCCP, Professor, Department of Clinical Pharmacy/ Department of Neurology, University of Colorado Denver, Academic Office 1, 12631 E. 17th Avenue, Room L15-1419, PO Box 6511, Aurora, CO 80045. E-mail: Jacci.Bainbridge@ucdenver.edu.
The content in this monograph was developed with the assistance of a medical writer. The authors made substantial contributions to the intellectual content of the articles by conceiving and designing the original presentations, researching references and studies, drafting the manuscripts, reviewing and revising the manuscripts, and/or providing supervision.