Introduction

Abstract

The introduction of disease-modifying therapies (DMTs) in the early 1990s profoundly changed the treatment of multiple sclerosis (MS). Before the advent of DMTs, few therapeutic options were available, and none was capable of altering the course of the disease (Lim & Constantinescu, 2010). Most patients diagnosed with MS faced the prospect of becoming wheelchair bound within a decade. Moreover, the likelihood of ongoing neurological deterioration portended a poor quality of life and a shortened life expectancy. Now, however, patients with relapsing forms of MS have access to DMTs that can significantly reduce the frequency and severity of clinical attacks, decrease the appearance of new symptoms, and slow the rate of disability progression (Lim & Constantinescu, 2010). Magnetic resonance imaging (MRI) studies have confirmed that these agents reduce the accumulation of damaged or active areas of disease (i.e., lesions or plaques) in the brain and spinal cord. In the United States, the DMTs approved for the treatment of relapsing-remitting MS (RRMS) are subcutaneous (SC) interferon (IFN) β-1a (Rebif, 2009), intramuscular (IM) IFN β-1a (Avonex, 2008), SC IFN β-1b (Betaseron, 2008; Extavia, 2009), SC glatiramer acetate (Copaxone, 2009), intravenous (IV) natalizumab (Tysabri, 2008), and IV mitoxantrone (Novantrone, 2008). (Note that natalizumab is administered under a stringent protocol and monitoring program because it has been linked to the development of progressive multifocal leukoencephalopathy, a potentially fatal brain disease). Although all the DMTs are indicated for RRMS, only IM IFN β-1a, IFN β-1b, and glatiramer acetate are approved for patients who have experienced an initial clinical episode and have MRI features consistent with MS, a condition known as clinically isolated syndrome (Avonex, 2008; Betaseron, 2008; Copaxone, 2009; Extavia, 2009). In addition, mitoxantrone is indicated for use in secondary-progressive MS (Novantrone, 2008). No DMT has yet been approved for primary-progressive MS. Despite the well-documented efficacy of DMTs in RRMS, the full benefits of these agents cannot be realized without long-term adherence to recommended regimens. Comprehensive management of MS requires the collaboration of professionals from different healthcare disciplines who can work with patients and caregivers to overcome the various obstacles to adherence. This supplement reflects the proceedings of a summit that was convened in Philadelphia, Pennsylvania, on August 22, 2009, with the goal of identifying practical strategies for encouraging proper adherence to DMTs. The participants included 3 neurologists, 2 nurse practitioners, a nurse, and a clinical psychologist, reflecting the multidisciplinary nature of MS care. The first article provides a review of the existing data on adherence. The second article focuses on factors that can influence patient adherence to DMTs, such as the level of family support, lifestyle stability, and the presence of depression. Also addressed are methods of maintaining adherence through constant educational reinforcement and involvement of care partners. The third article describes opportunities for education and advocacy that can positively influence adherence. Subjects such as risk-benefit analyses, work-related problems, and cognitive issues are discussed. Understanding the Pathophysiology of MS To fully appreciate the dynamics involved in adherence to MS therapy, one must first understand the impact of the disease itself. MS is a chronic neurologic illness characterized by damage to the myelin sheaths that protect long fibers, called axons, in the brain and spinal cord. The axons are responsible for carrying the electrical signals by which nerve cells communicate. When the insulating sheaths are damaged (demyelinated), the axons are no longer able to conduct signals effectively, resulting in impairments related to sensation, movement, and cognition, among other functions. Although the exact causes of MS remain unknown, both autoimmune and neurodegenerative mechanisms have been identified. An abnormal autoimmune response may result from factors such as exposure to an environmental agent (e.g., a virus) in genetically predisposed individuals. Once the immune system is triggered, activated lymphocytes (white blood cells) migrate across the blood-brain barrier and into the central nervous system (CNS). These lymphocytes interact with other cells inside the CNS and stimulate the production of inflammatory cytokines that break down the blood-brain barrier. The combined effects of this autoimmune response are demyelination, axonal damage, and formation of lesions. Axonal degeneration may begin early in the course of the disease and can lead to permanent neurological dysfunction. Brain atrophy may also occur early and is believed to reflect irreversible tissue damage. Disability results from permanent and irreversible axonal loss throughout the CNS. Diagnosis of MS Unpredictability is the rule in MS with respect to the disease course, type and severity of symptoms experienced by individual patients, and long-term outcomes. This heterogeneous nature can make the diagnosis of MS challenging. An estimated 400,000 people in the United States have MS. Onset of the disease usually occurs in early adulthood but can also occur during childhood. Women are more than twice as likely as men to be diagnosed with MS, and this gender trend may increase over time. Common symptoms (which may be mild, moderate, or severe) include fatigue, sensory or visual disturbances, weakness, bowel and bladder problems, and pain. Symptoms such as vertigo, tremor, speech difficulties, depression, cognitive changes, and sexual dysfunction may also be present. The symptoms of MS may appear as an acute attack (also known as an exacerbation or relapse) or may become chronic, with clinical and functional deterioration marking disease progression. Although MS is seldom fatal today, it continues to carry the threat of severe disability, with approximately one third of patients requiring ambulatory assistance within 10 years of diagnosis (Pittock, Maye, & McClelland, 2004). In the past, months or even years could pass between the actual onset of disease and the time MS was diagnosed on the basis of clinical symptoms alone. Today, however, the diagnosis is facilitated by the combined use of clinical observations, neuroimaging data, and sometimes laboratory tests. Criteria have been established for confirming the diagnosis on the basis of objective clinical evidence alone in some cases, the addition of MRI findings demonstrating dissemination of MS lesions in space or time in other cases, and further testing of evoked potentials and the cerebrospinal fluid in still other cases (Polman et al., 2005). Advances in the ability to diagnose MS have paved the way toward improving outcomes through the timely initiation of DMTs. Nevertheless, the degree of long-term benefit to be derived from these therapies depends heavily on adherence to treatment schedules. Factors Affecting Adherence to DMTs Although oral DMTs are under investigation, all the currently available agents must be administered parenterally. In the case of self-injected agents (IFN-β therapies and glatiramer acetate), patients or their caregivers must assume responsibility for adhering to the prescribed frequency of administration. The need to administer these therapies daily or multiple times per week can be a considerable obstacle to proper adherence. Patients may fear needles, tire of the inconvenience of injections, or have difficulty administering their injections. Furthermore, DMTs are commonly associated with side effects such as injection-site reactions, flu-like symptoms, and increased likelihood of depression, which can further discourage patients from adhering to a treatment that does not offer immediate benefits. Even mild bouts of these side effects may have a tremendous impact on adherence. Nurses and nurse practitioners can play an especially important role in helping patients to understand the risks and benefits of each DMT and to recognize the value of adhering to injection schedules. Nurses can be vital sources of practical information concerning the indications, effectiveness, and side effects of therapy, thereby facilitating patients' treatment decisions and ensuring proper use of these medications. Conclusions Recent advances in disease modification have changed the landscape of long-term MS care and have offered patients the prospect of a better future. It is hoped that the information offered in this supplement will encourage nurses to assume a proactive role in optimizing adherence to DMTs among patients with RRMS.Living With MS: Patient and Care Partner Perspectives