Journal of Neuroscience Nursing:
The Evolving Role of the Nurse in the Treatment of Multiple Sclerosis
Questions or comments about this article may be directed to June Halper, MSCN ANP FAAN, at email@example.com. She is the executive director of the Consortium of MS Centers and the International Organization of MS Nurses, Hackensack, NJ.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The underlying pathology can be both inflammatory and degenerative. It affects over 400,000 Americans per year and usually strikes in the prime of life. The disease can result in serious and debilitating impairment of physical, emotional, and cognitive functions that limit patients' overall status, halt their hopes and dreams, and alter their quality of life. To slow disease progression, administration of disease-modifying treatments early in the course of disease is thought to offer the best option for patients to achieve safe and effective management of this lifelong condition. This strategy, along with symptomatic management, encompasses the newest philosophy of comprehensive MS care. From an evidence-based understanding of MS, the role of the MS nurse has been transformed from a supportive, educative role to that of a highly skilled, knowledgeable and specialized professional. The nurse is a lynchpin in a multidisciplinary team dedicated to a patient's continuing care. In addition, the role of the MS nurse has evolved to incorporate supervising MS clinical trials, monitoring patients, implementing protocols, evaluating outcomes, and ultimately contributing to evidence-based practice. Although it is important that patients receive the appropriate therapy that may slow disease progression and manage symptoms, the individualized support provided by the MS nurse is essential to the sustained use of long-term treatments. Industry-supported nurse-administered patient assistance support programs, such as the Betaseron Education, Training and Assistance Nurse/BETAPLUSTM, MS Lifelines, Shared Solutions, and Avonex Services, employ nurses who offer valuable emotional, educational, and technical support to MS patients, ensuring that their needs are met throughout the course of therapy. These MS nurse specialist programs impart knowledge about self-administration of injections and facilitate self-management to reduce adverse events and promote sustained adherence. Regular contact with patients, a consistent level of care, a trusting relationship, and a greater understanding of prescribed treatment have resulted in increased adherence to complex protocols. As the specialty of MS nursing continues to evolve within the MS healthcare team, the MS nurse will continue to have a profound influence on treatment and improving quality of life in patients with MS.
The prevalence of chronic diseases is increasing, as is the complexity of the management of these conditions (Burden, 2003; Funnell, Kruger, & Spencer, 2004; Long, Kneafsey, Ryan, & Berry, 2002; Newbold, 1996, 2005). Medical advances have helped us understand many features of underlying diseases, resulting in the availability of new and improved therapeutic options for patients. Concomitantly, there is now an increased requirement for effective management of these treatments, often involving the concerted effort of a specialized healthcare team. Therefore, with the expanding demands of care and the recognition of the value of a multidisciplinary team, there is an increasing requirement for a practicing nurse to work effectively in balancing the many aspects of caring while still meeting the specific needs of each patient (Long et al., 2002). To care for patients with neurological disorders, nurses work in conjunction with a number of healthcare professionals, including neurologists, rehabilitation professionals, psychosocial specialists, and primary care practitioners (Porter & Keenan, 2003). Within this multidisciplinary team, the role of the nurse is to provide skilled and supportive patient care, including therapeutics, education, and the ongoing assessment of psychosocial needs, all of which are important factors for the effective management of any chronic disease (Burden, 2003; Funnell et al., 2004; Long et al., 2002; Newbold, 1996, 2005).
Multiple sclerosis (MS) is an example of a neurological disorder in which the nurse's role has increased since the early 1990s due to earlier diagnosis of MS, advances in effective treatments, and the integration of comprehensive care for long-term symptom management. MS is a highly variable and unpredictable disease and is one of the most life-altering diagnoses a person can receive (Holland & Madonna, 2005). Although an increasing number of pediatric cases have been identified during the past decade, MS generally strikes in adulthood, in the prime of life, often between the ages of 20 and 50 (National Multiple Sclerosis Society, 2009a). Four different clinical patterns of MS have been identified. The most common manifestation of MS, occurring in 85% of MS patients, is the relapsing-remitting form of MS (RRMS), which is characterized by unpredictable attacks or disease exacerbations (relapses) followed by periods of months to years of stability (remission), with no new signs or symptoms of disease progression (National Multiple Sclerosis Society, 2009a, 2009b). In RRMS, relapses may cause the patient's condition to worsen in a stepwise manner because of incomplete recovery following acute exacerbations. The progressive forms of MS include secondary-progressive MS (SPMS), primary-progressive MS (PPMS), and progressive-relapsing MS (PRMS). SPMS, which normally follows in most cases of RRMS after approximately 15 years, is characterized by slow but continuous deterioration of functions that may occur with or without exacerbations. PPMS is characterized by a continuous deterioration in function from the outset, where patients do not experience intermittent acute attacks. In contrast, PRMS, a rarer form of progressive disease, which also starts with declining functions from the outset, is characterized by additional clinical exacerbations.
To help diagnose patients in the early stages of MS, clinical expertise is combined with ancillary tests such as magnetic resonance imaging (MRI). New and recently revised McDonald criteria for the evidence of dissemination of lesions in space and time are now commonly employed in the diagnosis of MS (Goodin et al., 2002). Several MRI findings are used to confirm neurological abnormalities in MS patients: contrast-enhanced T1-weighted scans or lesions are used to assess permeability of the blood-brain barrier (BBB); T2-weighted scans or lesions provide information on the extent of brain tissue injury and reduction of total brain volume, and measuring brain atrophy evaluates a process of irreversible tissue loss occurring in the brain, a hallmark of MS. As the disease progresses, the number of relapses decreases as a function of the natural history of MS, but changes due to MS are reflected in brain atrophy and an increase in T2-weighted lesions (Lazeron et al., 2005). Although not a day-to-day monitor of MS activity, MRI has emerged as a window on MS in clinical trials and has assisted investigators in determining disease patterns in particular populations. Therefore, with respect to modifying the disease, the main treatment goals for MS include the reduction of number, severity, and frequency of relapses throughout the course of the disease and a decrease in contrast-enhanced T1-weighted lesions and T2-weighted lesion load to delay or prevent brain atrophy and the onset of permanent disability (Barkhof, 2004; Lazeron, de Sonneville, Scheltens, Polman, & Barkhof, 2006). Nursing goals of treatment are to help MS patients achieve optimal clinical and psychosocial function and quality of life.
Although there are treatment options for RRMS and SPMS, as discussed later in more detail, currently no approved treatments are available for the progressive form of the disease. Sensible management of clinical symptoms of the progressive forms of MS and prevention of complications are essential strategies employed to avoid the consequences of untreated problems, such as bowel and bladder dysfunction, pain, spasticity, fatigue, and the hazards of immobility. Cognitive impairment, which can affect patients' ability to process information, does not always correlate well with the length of illness, degree of physical disability, or disease course. It is important to be aware that a person with MS may be very disabled without cognitive dysfunction or, conversely, may have significant cognitive impairment without any physical disability (National Multiple Sclerosis Society, 2009a, 2009b). These unpredictable variations in presentation make MS a very complex condition for a patient to manage on his or her own.
Using the analogy of the growth and development of an infant to adulthood, the care received by the patient from the time of diagnosis and throughout the course of MS is key to successful adaptation to the impact of the disease and long-term recovery (Porter & Keenan, 2003; Warner, Thomas, & Martin, 2005). Advances in the treatment of MS over the last decade have led to the need for highly skilled nurses, equipped to meet the healthcare, educational, and psychosocial needs of patients across the continuum of the disease course. The expanding responsibilities of MS nurses have resulted in the addition of new roles and required more intense specialization. This article provides an overview of the increasingly important role of the nurse in providing care to patients with MS.
The Evolving Role of the MS Nurse
A review of the literature has documented the role of the nurse in chronic disease and disability management and, most recently, in the case of those affected by MS (Denis et al., 2004; Dhib-Jalbut, 2002; Holland & Madonna, 2005). Due to the recent expanding management strategies and approaches to MS treatment, the nurse's role has, in turn, evolved (Costello & Halper, 2005). The MS nurse has had to become more specialized, fulfilling new roles in a number of settings ranging from primary care, specialty settings, rehabilitation, and long-term care (Costello & Halper, 2005). There is now a large population of MS-certified nurse specialists working within the neurology field worldwide. As of late 2006, there were over 450 nurses who are certified MS nurses. The International Organization of MS Nurses (IOMSN) provides numerous forms of nursing education that offer a comprehensive overview of MS for nursing professionals (International Organization of Multiple Sclerosis Nurses, 2009). It offers courses to cover such topics as the definition of the role of an MS nurse, discussions on evidence-based practice in disease modification and symptom management, strategies for psychological support, and current research priorities in MS (International Organization of Multiple Sclerosis Nurses, 2009). Through publications provided by the IOMSN and via the IOMSN Web site, issues in patient management and skill development are addressed by MS nurse experts.
Assessing and targeting the treatment of MS symptoms have always been areas in which the MS nurse takes a primary function. Autonomy is a key factor as nurses develop and implement complex care plans while efficiently managing their time and workload. The MS nurse is accountable for the quality of the care he or she provides, patient satisfaction, and the efficient use of resources. The role of the MS nurse can be very similar to that of the case manager, frequently requiring him or her to direct resource management and clinical systems development. The nurse has always taken an active role in the MS clinical setting by interacting with patients and their families as an educator, counselor, advocate, and caregiver. The MS nurse's educational responsibilities include providing patients and families with information about the implications of a diagnosis of MS, the pathophysiology of the disease, prognostic indicators, and pharmacologic and nonpharmacologic management. A key role of the nurse is to set realistic patient expectations with regard to lifestyle and treatment options. By using highly specialized knowledge and experience, the MS nurse is able to dispel misconceptions about the disease, interpret research findings, and empower patients by encouraging them to make informed decisions.
As a pivotal member of the MS healthcare team, the MS nurse collaborates with a variety of disciplines to ensure that patients receive appropriate care and follow-up. The MS nurse can function in a role coordinating research efforts in clinical trials, which involves performing physical examinations, ensuring that patients comply with protocols, and evaluating outcomes. Since the emergence of comprehensive care in the mid-1960s, it has become imperative that the MS nurse has an in-depth knowledge of the course of disease, its symptoms, how it is diagnosed, and long-term implications of the disease and treatments. The nurse is also expected to provide advice to the patient to influence the patient's state of wellness. As an advocate, MS nurses negotiate on behalf of patients with employers, insurance companies, and other external agencies. As advocates for staff members, MS nurses provide emotional and situational support for nursing and other staff members. They work to prevent and resolve conflicts, reduce stress, and improve clinical judgment. These are the characteristics of the MS nurse expert.
The Evolution of Disease-Modifying Therapies
The pattern of MS care has changed significantly over the last few decades. During the 1970s and 1980s, treatment focused mainly on palliative care and symptom alleviation (Costello & Halper, 2005). Along with increased understanding of the underlying immunology and pathogenesis of MS, therapies have now been developed to target the inflammatory components underlying the disease rather than simply managing the symptoms (Rizvi & Agius, 2004). Current evidence regarding the mechanism of disease rests on an autoimmune-based model, in which the principal cause of disease begins with the activation of autoreactive T cells that drive the pathogenesis of MS (Dhib-Jalbut, 2002). Autoreactive T cells are thought to become proinflammatory (Dhib-Jalbut, 2002), cross the protective BBB into the central nervous system (CNS), and attack the myelin sheath. It is thought that once these cells enter the CNS, release of inflammatory mediators such as proinflammatory cytokines contribute to the tissue breakdown (Dhib-Jalbut, 2002). Development of relapses and new lesions on MRI are related to the demyelination of axons and subsequent irreversible axonal transection because of chronic inflammation in the CNS. At this time, it is unclear whether axonal damage is a result of this process, a precursor to inflammation, or is totally independent of T-cell activity. It is equally difficult to pinpoint the pathologic origin of the widespread and fluctuating symptoms of MS along with the inability to predict long-term outcomes of the disease. Recently, there has been an increased interest in the role of B cells, inflammatory cytokines, and genetics to explain the variability of the disease. There is also ongoing research in the area of neuroprotection to prevent permanent, irreversible tissue destruction. Even as greater insights into the pathophysiology of MS have led to the availability of disease-modifying agents, the growing array of treatment options and management strategies have led to the emergence of MS nurses as pivotal members of the MS healthcare team.
Since the mid-20th century, corticosteroids have been used to treat and hasten recovery from relapses. Immunosuppressants, such as cyclophosphamide or azathioprine, were thought to have some impact on the overall disease course (Lublin, 2005). It was not until the late 1980s that the concept of using immunomodulation to treat the disease was introduced (Lublin, 2005). The current platform therapies for the management of MS are the disease-modifying therapies (DMTs) that target the pathophysiology of the disease based on evidence from laboratory studies and clinical trial data. The treatments now approved for relapsing forms of MS by the US Food and Drug Administration are the following: interferon (IFN) β1-a (Avonex and Rebif), IFN β1-b (Betaseron), and glatiramer acetate (GA; Copaxone), which specifically target the inflammatory pathogenesis of MS (Dhib-Jalbut, 2002). Mitoxantrone (Novantrone), an infusible immunosuppressant approved for use in the United States in 2000 for worsening relapsing forms of MS, and natalizumab (Tysabri), an infusible monoclonal antibody for relapsing MS that is also associated with immune suppression, are now among medications that increase the possibilities for managing disease activity. Natalizumab is approved as a monotherapy for the treatment of RRMS through a special restricted distribution program called the TOUCH Prescribing Program, in which only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse the product (Biogen Idec, Inc.)
The IFN β (IFN β1-a and IFN β1-b) class of DMTs interferes with T-cell activation by counteracting the effects of IFN γ, which is believed to have an active role in the pathogenesis of MS by activating T cells, which then cross the BBB (Dhib-Jalbut, 2002). The mechanism of action of GA is not fully understood, but it is thought to have a number of immunologic effects, including blocking T-cell activation, thereby inhibiting inflammatory action (Dhib-Jalbut, 2002). There is emerging evidence in the literature that both IFN β and GA may have neuroprotective effects (Rieckmann, 2005; Vajda, 2002; Yong, 2002; Ziemssen, 2004). However, this is still an area requiring more study because the definition of neuroprotection itself lacks consensus. The hope is that as knowledge of this area increases, an accumulation of evidence may provide an immunologic model for neuroprotection. Mitoxantrone is a deoxyribonucleic acid intercalator that inhibits B-cell, T-cell, and macrophage proliferation and impairs antigen presentation and the secretion of IFN γ and the cytokine interleukin-2 (Serono, Inc., 2006). The specific mechanism of action of natalizumab is also not fully understood, but it is thought to interfere with the interaction of adhesion molecules between the T cell (very late antigen 4) and endothelial cells (vascular cell adhesion molecule) on the BBB, preventing T cells from crossing the BBB (Serono, Inc., 2006). An overview of the DMTs currently available for the treatment of MS and their mode of administration and dosing schedules is presented in Table 1.
Because of the current armamentarium of MS treatment, physicians and nurses are now able to discuss therapy options that best meet the patient's individual disease course and lifestyle considerations (Goodin et al., 2002). With the advent of DMTs, the prognosis of relapsing MS patients has improved significantly. Data are now available from pivotal clinical trials and long-term studies, which demonstrate the clinical efficacy of IFN β1-a (Clanet, Kappos, & Radue, 2001; Cohen, Goodman, & Heidenreich, 2001; Comi, Filippi, Barkhof, et al., 2001; Jacobs et al., 1996, 2000; Li & Paty, 1999; Li, Zhao, & Paty, 2001; PRISMS Study Group, 1998, 2001; Rudick et al., 1997; Simon et al., 1998; SPECTRIMS, 2001), IFN β1-b (European Study Group on Interferon Beta-1b in Secondary Progressive MS, 1998; Goodkin & TNASS, 2000; Paty & Li, 1993, 2001; The IFNB Multiple Sclerosis Study Group, 1993; The IFNB Multiple Sclerosis Study Group & The University of British Columbia MS/MRI Analysis Group, 1995), and GA (Comi, Filippi, & Wolinsky, 2001; Johnson et al., 1995).
The pivotal IFN β1-b study (The IFNB Multiple Sclerosis Study Group, 1993) that led to the 1993 Food and Drug Administration approval of this agent for RRMS treatment was a multicenter, randomized, double-blind, placebo-controlled trial in which 372 RRMS patients received either placebo or IFN β1-b (250 or 50 μg) subcutaneously (SC) administered every other day. After 2 years of treatment, IFN β1-b significantly reduced the clinical relapse rate (−34%) and severity of exacerbations as compared with placebo; in addition, IFN β1-b statistically significantly reduced MRI activity, as measured by a reduction in T2-weighted lesions (−80%) and the appearance of new T2-weighted lesions (−83%) when compared with placebo, suggesting that IFN β1-b decreased accumulation of MRI abnormalities and altered the natural history of MS in these patients. This trial showed that high-dose, high-frequency IFN β1-b was an effective, well-tolerated treatment for RRMS patients, with no serious side effects reported. The 16-year long-term follow-up to this study will provide the longest term data on treatment outcomes with any IFN β. Final results of this study presented at the American Academy of Neurology 2006 Annual Meeting in San Diego were promising. The full report of this study will provide cross-sectional data of patients enrolled in the original pivotal trial, including survival rates, disease status, relapse rate, Expanded Disability Status Score (EDSS; outcome measure for clinical trials based on neurological examination), adverse events, and MRI measures examined in patients exposed to treatment compared with natural history data (Ebers et al., 2006).
A pivotal study of intramuscularly (IM) injected IFN β1-a (Avonex; Jacobs et al., 1996) had a similar trial design as the IFN β1-b study, in which 301 RRMS patients were treated once weekly with either placebo or IFN β1-a (30 μg/week) for 2 years (Jacobs et al., 1996). Approximately half of the patients (172, 57%) entered the trial early enough to be followed up for 104 weeks following the end of the trial. As seen with the IFN β1-b trial, IFN β1-a IM treatment, when compared with placebo, resulted in a statistically significant improvement in both clinical and MRI outcomes, as measured by reductions in EDSS progression rate (−37%), clinical attack rate (−18%), and MRI attack rate (measured by the median number of contrast-enhancing lesions on T1-weighted scans [−33%]).
The pivotal study for SC injected IFN β1-a (PRISMS Study Group, 1998) used a similar study design as the previously described trials, with 560 RRMS patients randomized to placebo or IFN β1-a (22 or 44 μg) SC three times weekly for 2 years. After 2 years of treatment, when compared with placebo, IFN β1-a SC provided both clinical and MRI benefits, as seen by statistically significant reductions in the clinical attack rate (−32%), MRI attack rate (as measured by the median number of active T2 lesions [−78%]), and reduction in EDSS progression rate (−30%).
These trials provided evidence that IFN β, as a class, decreases the frequency of relapses from 18% (IFN β-1a IM) to 34% (IFN β-1b) and also inhibits the development of new lesions, as shown by MRI (Goodin et al., 2002, 2007). Although results differ across trials, some studies have demonstrated that compared with low-dose therapy, high-dose high frequency IFN β administration showed a more significant reduction in the severity of attacks and delay of onset of disability (Durelli et al., 2002; Goodin et al., 2002).
For non-IFN β therapies, GA is perhaps one of the most widely used regimens to treat RRMS patients. A study investigating the effect of GA on relapse rate in RRMS patients enrolled 251 patients who were randomized to receive either placebo or GA at 20 mg daily by SC injections for 2 years. Results showed a 29% reduction in relapse rates in patients treated with GA versus placebo (p = .007). In addition, a higher proportion of patients on GA had improved EDSS scores compared with the proportion of patients who received placebo (Johnson et al., 1995). In a subsequent trial investigating the effects of GA on MRI activity in patients with RRMS, there was a significant decrease in total number of contrast-enhancing lesions on T1-weighted scans with GA compared with placebo (p = 0.003), as well as a decrease in relapse rate in 33% of GA-treated patients (Comi, Filippi, & Wolinsky, 2001). There was a consistent favorable outcome for many MRI outcome measures, including number and volume of contrast-enhancing lesions on T1-weighted scans and number of new T2-weighted lesions. Therefore, GA showed significant benefit in decreasing disease activity, as measured by clinical and MRI parameters.
There have been several trials investigating the efficacy of DMTs in SPMS patients with and without relapse (Cohen et al., 2001; European Study Group on Interferon Beta-1b in Secondary Progressive MS, 1998; Goodkin & TNASS, 2000; SPECTRIMS, 2001). Investigators examined changes in EDSS, clinical measures, and MRI outcome findings. These trials confirmed the ability of IFN β to reduce relapses and MRI lesions but showed conflicting results in disability prevention. Therefore, specific treatments that may benefit and improve the lives of SPMS patients remain an unmet clinical need.
An increasing body of evidence suggests that DMTs can make a more drastic difference when patients present with a first demyelinating attack suggestive of MS clinically isolated syndrome (Lublin, Baier, & Cutter, 2003; Thompson et al., 2000). The hypothesis has been that early treatment can delay the onset of a second attack confirming the diagnosis, which would be associated with a potential for more damaging pathology. The Early Treatment of MS trial, investigating the effect of IFN β-1a SC versus placebo in 278 randomized patients for 2 years, demonstrated a reduction in the risk of progression to clinically definite MS (CDMS) by 11% (2-year result) and lower MRI lesion burden in the IFN β-1a SC treated group (22 μg/week; Comi, Filippi, Barkhof, et al., 2001). The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study, which investigated the effect of IFN β-1a IM (30 μg/week) versus placebo in similar groups of patients presenting with an acute demyelinating event, showed a reduced risk of development of CDMS of 44% at 2 years and decreases in new and enhancing MRI lesions (Jacobs et al., 2000). Recently, patients with a first demyelinating event were randomized in a placebo controlled trial, the Betaseron in Newly Emerging MS for Initial Treatment study. This study was designed to assess the efficacy of IFN β-1b (250 μg SC every other day) on the progression of clinically isolated syndrome to CDMS according to the Poser criteria and MS according to the McDonald criteria. The latter criteria can help diagnose MS much earlier than the Poser criteria can. Results from this study showed that the IFN β-1b led to a significant reduction in the risk of conversion to CDMS (by 50% at 2 years) and in the risk of conversion to definite MS by McDonald criteria (by 46% at 2 years) to both CDMS and definite MS using the McDonald criteria, recently revised by an international panel (Kappos et al., 2006). All of the studies relied on MS nurses, who provided an invaluable contribution worldwide in sustaining adherence throughout these difficult yet important studies.
Treatment Adherence Issues
The management of MS is fraught with complex treatment protocols (Costello & Halper, 2005). A key element in positive outcomes in chronic diseases is initiating and sustaining therapy. This is an important part of MS management that, as early as 1997, was discussed by MS nursing experts. If patients are to be treated in the early stages of MS to improve long-term outcomes, adherence to therapy becomes an even greater challenge due to the invisible stage of the disease and the increased duration of treatment (Costello & Halper, 2005). In addition, symptomatic care of confounding symptoms (bowel, bladder, pain, spasticity, and fatigue) poses both pharmacologic and nonpharmacologic challenges to MS patients and their families. With MS, as with any other chronic disease, a number of elements need to be considered to promote treatment adherence. These are mainly connected with patients' history of contact with healthcare, ethnic and cultural variables, and socioeconomic circumstances and also include issues with communication, knowledge, physical impairments, financial concerns, emotional distress, and psychiatric status (Denis et al., 2004; Halper, 2006).
Because MS, in itself, is such a complex disease, MS nurses caring for the patient are faced with numerous difficult and evolving clinical challenges (Denis et al., 2004; Dhib-Jalbut, 2002). The disease is multifaceted and dynamic; symptoms and their intensities can vary greatly from patient to patient, and each case differs. Individual differences depend on the presenting symptoms (Holland & Madonna, 2005) and the patient's outlook on the disease, among other factors (Denis et al., 2004). Since the approval of DMTs in the MS treatment paradigm, the role and responsibilities of the MS nurse have expanded to encompass increasing education and healthcare management needs (Halper, 2006). As with any self- or family member-injected medication, patients may experience pain and discomfort due to the injection itself or may have needle phobia leading to poor injection technique. All disease-modifying agents are available for relapsing forms of MS under most insurance carriers. Of course, issues such as high copayments or a substantial deductible on one's insurance policy may be barriers to adherence to medication. Most Medicare D carriers cover the cost of MS DMTs, but the extent of coverage varies with each policy. Several years ago, Medicare B approved the use of Avonex if the physician purchased the medication and administered it in the office once a week. This has changed with the advent of Medicare D, although it has been this author's experience that some patients prefer to have the injection administered in their physician's office due to lack of family support to perform the injection or inability to self-administer an IM injection. All these factors may contribute to an inconsistent injection routine along with lack of belief in the therapy, resulting in poor adherence to treatments. Although the current view of MS appears more positive to healthcare providers possibly because of new insights into the complexities of the disease, therapeutic advances, and comprehensive care (Halper, 2006), this impression must be conveyed and constantly reinforced to patients and their families. The MS team, including the MS nurse and social support network of the patient, must work together to support and sustain an individualized and optimal quality of life despite the presence of MS. When developing an individualized plan of care, the age and stage of development of each person must be considered, including who they are, where they come from, and who they would like to continue to be.
It is also important to acknowledge that although DMTs are effective, they are partial therapies because they do not totally eliminate relapses or ongoing symptoms. When a relapse occurs, this can result in a time of crisis, which is a particular challenge to the patient and his or her healthcare team (Warner et al., 2005). In this situation, it is important that the patient feels that there is a good support network behind him or her and that there is someone who understands the implications of the sudden reappearance of a disease that may have disappeared for a while. In a research study conducted within a district general hospital in the United Kingdom, patients reported their symptoms to a nurse sooner (within 10 days of onset) as compared with a mean reporting time of 51 days to their physician (Warner et al., 2005). This was thought to be due to the one-to-one contact and the immediate availability of the MS nurse. The nurse, in turn, was able to readily explain the nature of the relapse and organize the appropriate appointments and follow-up. Reports of the patients' relapse via the nurse have been shown to occur in a shorter time frame compared with the patients having to report their symptoms to their physician, 6 days compared with 14 days, for nurses and physicians, respectively (Warner et al., 2005). If the patients feel that they are being supported and receiving prompt care in a short space of time, this will increase patients' confidence and belief in the healthcare system.
Monitoring the patient's disease activity through continual review and documenting the treatment's success are parts of the MS nurse's responsibilities (Warner et al., 2005). The MS nurse has been shown to be pivotal in organizing any additional intervention with areas that require assessment and care from the patient care team. The MS nurse has become a major force in evidence-based practice, including aspects such as diminishing injection site erythema, reducing pain, and preventing infections through skills and knowledge (Denis et al., 2004; Namey, 2007). With the use of IFN β, nurses have been pivotal figures in the development and optimization of dose titration, injection site rotation, and pain reduction (Halper, 2006).
Patient Assistance Programs
In further recognition of the need for specialized support, numerous patient assistance programs are sponsored by the makers of the approved DMTs. Specific nurse-directed programs (e.g., Betaseron Education, Training and Assistance [BETA] Nurse/BETAPLUSTM programs; these programs will be discussed in greater detail in the next sections) also are proving successful in offering high-level patient assistance. An important aspect of patient-centered projects that are administered by nurses is the ability for the program to continually evolve based on the dynamic needs of patients and their families. The expectations of the patient are constantly changing; because patients are being diagnosed much earlier and at a younger age, there is a requirement that programs and services reflect the age, stage of development, and circumstances at those particular times. This, coupled with the fact that there has been a considerable increase in patient knowledge regarding the disease and the therapies available, implies that flexibility and vitality of nurse-administered programs is increasingly important.
The company-sponsored support programs currently available to MS patients that treat thousands of patients (Biogen, Inc., Avonex) are summarized in Table 2; each of these programs is discussed in more detail in the next sections.
Betaseron Education, Training and Assistance Nurse/BETAPLUSTM
The BETA Nurse/BETAPLUSTM program is sponsored by Bayer Healthcare Pharmaceuticals, the makers of IFN β1-b (Bayer Healthcare Pharmaceuticals, 2006a; Madonna & Keating, 1999). The BETA Nurse program is unique in that it is a wholly nurse-coordinated service, with 78 specialist nurses enrolled to date. This individual service provides support to MS patients taking or considering IFN β1-b therapy (Bayer Healthcare Pharmaceuticals, 2006b). The service is run by specialist MS-certified nurses throughout the United States, known as BETA nurses. Although the BETA Nurse program is specifically centered on the MS patient, the program also offers unique opportunities for the nurse and provides a special nursing career track. The program provides nurses with at least 2 months of internal training, after which the nurse (paired with a mentor) works with MS patients in the home setting or at a physician's office. BETA nurses are also encouraged to sit for the IOMSN examinations within 2 years of starting the program.
Trained and experienced BETA nurses provide support to MS patients in a number of ways, both in person (home visits or at a physician's office) and via telephone, and all patients are offered the same regular contacts (Bayer Healthcare Pharmaceuticals, 2006a). Providing a regular contact who can provide support in the home is an important factor of patient care because some patients may find traveling to the hospital or center difficult. This becomes increasingly important if the patient has impaired mobility (Warner et al., 2005). The BETA nurse initiates telephone counseling and in-home training with the patient, where the nurse provides instruction on the appropriate injection techniques. The BETA nurses provide consistent follow-up and record the patient's progress with therapy, including the monitoring of adverse events and tolerance to treatment over time (Bayer Healthcare Pharmaceuticals, 2006a). Additional services offered by the program and advocated by the BETA nurse include invitations to bimonthly seminars that cover educational issues, a platform to share personal experiences with other MS patients, listings of local events, and a newsroom service with which patients are able to view the latest developments in MS online and find information regarding reimbursement. The BETA Nurse program has been one of the most successful nurse-coordinated services, and as such, several elements of the program have been incorporated into other support programs. Coordination with BETAPLUSTM, a patient support program that is available to patients 24 hours a day, 7 days week, has helped distinguish the BETA nurse as an excellent support system for patients.
Shared Solutions is a program sponsored by Teva Neuroscience, the manufacturers of GA. It is a free program that is designed to help people with MS, their families, and their caregivers (Teva Pharmaceutical Industries Ltd., 2006). The Shared Solutions service is individually tailored to the patient using the collective knowledge of leading medical experts in the field of MS, including nurses. The program aims to help MS patients overcome the challenges of living with the disease and is open to patients who are not receiving GA therapy. The support services offered by the Shared Solutions include a telephone service where trained professionals (certified MS nurses) can be reached for advice such as injection administration tips and information regarding GA therapy. Shared Solutions also organizes events including live discussions and educational programs and advice regarding reimbursement issues. The program also provides an MS-focused Web site along with downloadable resources. Shared Solutions nurses are encouraged to become MS certified and to sustain continuing education and information related to their field of expertise. Certain regions of North America now have specialist nurses to provide injection training in patients' homes.
Avonex Services is a program sponsored by Biogen, makers of IFN β1-a IM (Biogen Idec, Inc., 2009). The service offers an Avonex case manager, a person who is knowledgeable about MS and gives guidance and support to the patients in continuing with their therapy in the long run. The Avonex case manager can provide information on a range of issues, from assistance with reimbursement matters to injection training. The program also provides a therapy support coordinator, who can help the patient take advantage of a wide variety of valuable resources that will help get the most out of the treatment. As part of the support to meet the patient's treatment goals, Avonex Services offers injection training, which includes managing injection anxiety and managing common side effects related to treatment, as well as providing advice about treatment expectations and personal support via telephone or on a one-to-one contact within the patient's own home. Other services offered in the program include the Online Mentor program, which allows MS patients to search for or become an MS mentor who will develop into an advocate and support other MS patients by sharing their experiences; the circulation of educational material about MS to empower the patient; and the Live MS events, a forum for sharing their personal experiences with others.
MS LifeLines is an educational and support program sponsored by EMD Serono, Inc. (2006) and Pfizer, Inc. EMD Serono is the manufacturer of IFN β1-a administered SC three times per week. The MS LifeLines program is multifaceted and provides ongoing patient education and assistance through a number of services including reimbursement, informational services, and assistance with Medicare D, as well as facts, tips, and educational support provided by MS-certified nurses for patients receiving SC IFN β1-a treatment. MS LifeLines also provides a range of educational materials and programs, including a Patient Toolkit for MS; booklets concerning the disease and management issues; Connecting, Helping, Assisting, and Teaching (CHAT) programs; and information regarding SC IFN β1-a therapy.
Members of MS LifeLines can attend programs with "Rebif patient ambassadors" (people living well with MS), an important aspect of patient-support programs, because it enables patients to have role models and sustains continued hope in coming to terms with and coping with their MS diagnosis. Members of the program can also have live discussions via the Web or by telephone, providing help and support to the patient. MS LifeLines nurse educators are MS-certified nurses who provide injection training for SC IFN β1-a and personal assistance to patients and families beginning or sustaining SC IFN β1-a therapy in many areas of the United States. The nurses then provide ongoing follow-up until patients are able to assume more responsibility for self-management. MS LifeLines nurses and the MS LifeLines nurse educators in the field are encouraged to sit for the specialist examination and attend ongoing nurse education programs.
Lessons Learned From Nurse-Administered Patient Assistance Programs
One of the most valuable elements of any nurse-administered patient assistance program is the influence that it can have on patient management. For example, preliminary evidence from the Shared Solutions program has suggested that patients beginning therapy with GA who are at risk of nonadherence are more likely to remain on therapy when paired with Shared Solutions nurses (personal communication with B. Beach, Shared Solutions MS Nurse). Another important aspect of these programs is the evaluation of the data that they generate, including insight into the reasons patients switch between therapies and the reasons why they might continue with a specific treatment option (Shapiro, 2005). From the perspective of a program's impact, identification of areas that have provided the greatest benefit to MS patients can be clearly identified, as can areas that need improvement. Importantly, the patient's sense of hope and direction is maintained, which is fundamental in chronic diseases such as MS.
Through the analysis of valuable data gathered by these MS-nurse-administered programs, one of the most common reasons for treatment discontinuation was found to be the result of discomfort associated with injection site reactions (redness, itching, bruising, or swelling). The MS LifeLines program has helped to provide support, education, and training, along with management of injection site technique, to help decrease the incidence of injection site reactions. In addition, the program has provided valuable insight into how the introduction of simple autoinjectors with finer gauge needles may go some way to help with patient adherence. Data were gathered from the MS LifeLines program database before and after the introduction of the Rebiject II autoinjector (Scanzillo et al., 2006). During the period before the autoinjectors were introduced, 13,333 patients received SC IFN β1-a, and of these patients, 2,352 patients discontinued treatment. Of these 2,352 patients, 209 (8.9%) discontinued due to injection site reactions, and 187 (8%) discontinued due to pain and/or burning at the injection site. In regard to the time to discontinuation, 340 (14.5%) patients discontinued within the first 6 months of therapy, and 213 (9.1%) discontinued within the first 3 months. When data were analyzed in the period after the introduction of the autoinjectors, 13,691 patients had received SC IFN β1-a, and of these, 2,454 patients discontinued treatment. Dramatic decreases in discontinuation due to injection site reactions were seen after the introduction of the autoinjector; 131 (5.3%) patients discontinued due to injection site reactions, and 45 (1.9%) of the patients discontinued due to pain and/or burning at the injection site. Also, there were decreases in the numbers of patients discontinuing within 3 and 6 months of therapy, with 72 (2.9%) patients at 3 months and 132 (5.4%) by 6 months. These data reflect the importance of how the introduction of injection tools to ease problems such as injection site reactions promotes patient adherence, especially during the first 6 months of starting treatment (Scanzillo et al., 2006).
An outstanding data set on adherence has emerged from the BETA Nurse program, which was implemented to provide healthcare providers, patients taking IFN β-1b, and their families a comprehensive disease management program that can provide information on the elements of training and support. Patients are encouraged to provide feedback on aspects of the program that they find most and least valuable, in a continuous effort to improve the services offered (Shapiro, 2005). Data generated from the BETA Nurse program have also indicated that the implementation of simple techniques to minimize and manage treatment adverse events and the promotion of good injection site technique has a positive impact on treatment adherence (Denis et al., 2004; Shapiro, 2005).
The BETA Nurse program is an ongoing service, and since the start of the project, over 10,000 patients have participated (Shapiro, 2005); the data generated to date have shown that patients involved in the program are extremely likely to remain on therapy. A total of 88% of patients enrolled in the program remained on IFN β1-b 13 months after the start of the treatment compared with 63% patient retention seen in historic controls and 45% for IM IFN β1-a and GA at 48 months (Shapiro, 2005). Reasons for this impressive patient retention rate may be due, at least in part, to the support offered by the BETA Nurse/BETAPLUSTM program, the considerable attempts made by the BETA nurses to contact patients, and their ability to provide empathic and committed long-term support (Shapiro, 2005).
As this and other programs continue to evolve, it is expected that more patients will participate. Data from these programs can be utilized to provide insight and further enhance nurse support services offered to MS patients and their families by industry and in individual practices. These programs, although industry sponsored, have embraced the MS specialist concept. Most nurses employed by the MS pharmaceutical industry are required to study MS thoroughly and sit for the MS nursing certification examination. The credentials, Multiple Sclerosis Certified Nurse, attest to the value placed on this specialty and are the impetus for many collaborative activities during national and regional meetings in the United States and Canada.
There is increasing complexity of MS patient care in the era of DMTs, and several factors, both common to all chronic diseases and unique to MS, are important for the achievement of optimal treatment outcomes. Nurses are often the main day-to-day contact person for patients. They play a pivotal role in producing positive clinical, psychosocial, and quality-of-life outcomes in MS. As the MS treatment paradigm continues to evolve, it is anticipated that the MS nurse will remain at the forefront of the multidisciplinary team of healthcare professionals dedicated to optimizing outcomes through research, education, and the identification and implementation of best practices. Consequently, specialized nursing support and nurse-administered patient assistance programs are becoming a desirable model of care in MS. The success of pharmaceutical-industry-sponsored patient support programs such as the BETA Nurse program, Avonex Services, Shared Solutions, and MS Lifelines illustrates the nursing impact of the provision of personal assistance, reimbursement support and patient training, education, and skills development. This has had a positive impact on patient adherence to treatment, and continued evaluation of this model of care can only result in sustained benefits for the MS community. The team approach focusing on scholarly inquiry, evidence-based practice and dynamic models of care appears to be the best philosophy in managing MS throughout a patient's lifetime.
The author would like to thank Medicus International for the editorial assistance, which was funded by Bayer Healthcare Pharmaceuticals.
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