Injectable disease-modifying therapy for relapsing-remitting multiple sclerosis: a review of adherence data.
Patient compliance (Management)
Medical care surveys (Methods)
|Publication:||Name: Journal of Neuroscience Nursing Publisher: American Association of Neuroscience Nurses Audience: Professional Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2010 American Association of Neuroscience Nurses ISSN: 0888-0395|
|Issue:||Date: Oct, 2010 Source Volume: 42 Source Issue: 5|
|Topic:||Event Code: 200 Management dynamics Computer Subject: Company business management|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Long-term adherence to disease-modifying therapy in relapsing-remitting multiple sclerosis (RRMS) is associated with improved patient outcomes, including a reduced risk of relapse and a better preserved quality of life. However, the unpredictable nature of the disease---even when it is being treated--may make it difficult to convince patients of the importance of treatment adherence. A number of studies have attempted to pinpoint factors that affect adherence. Nursing interventions that address some of these factors may improve adherence and, thus, the disease course for a variety of RRMS patients. This article summarizes literature that approximates the prevalence and impact of nonadherence and reviews factors identified in clinical trials that affect adherence. Nursing interventions that can improve adherence, including telephone counseling and motivational interview techniques, are also addressed.
Long-term adherence to therapy is vital for people living with a chronic condition such as multiple sclerosis (MS). However, evaluating research on the topic of adherence is hampered by the lack of consistency of the methods used between studies. Currently, the available information concerning adherence provides glimpses that have identified potential causes of nonadherence, but the evidence about the balance between adherence/nonadherence does not generate an adequately detailed "road map" for patients and their healthcare providers to follow to yield the best benefits.
Studies have shown that the best prospects for reducing the risk of relapse, optimizing functional and cognitive abilities, and preserving quality of life are enhanced when patients adhere closely to recommended regimens (Devonshire et al., 2006; Fraser, Margante, Hadjimichael, & Vollmer, 2004). Notably, however, many patients may not experience relapses or significant symptoms for months or years after being diagnosed with MS--a fact that may make it difficult for them to accept the need for careful attention to prescribed care (Costello, Kennedy, & Scanzillo, 2008). Conversely, disease exacerbations necessitating changes in treatment can occur even in the face of good adherence (Fraser et al., 2004). Consequently, patients may believe that adherence provides little protection against a therapy "failing," undermining their motivation to adhere to subsequent treatments. In this review, the prevalence of nonadherence, the factors affecting adherence, and the nursing interventions that can affect adherence are discussed. Nursing interventions designed to address these and other obstacles can help patients and their caregivers develop the skills necessary for good adherence. Measures aimed at achieving this goal may contribute toward reducing the toll of nonadherence.
Prevalence of Nonadherence
Adherence is defined as the ongoing, voluntary, and collaborative involvement in a mutually acceptable behavior that results in a therapeutic outcome, unlike compliance, which is how well a patient follows the clinical prescription and recommendations (Namey, 2007). Continuous, long-term use of disease-modifying therapy (DMT) to treat MS provides the greatest benefit by preventing relapses and delaying disease progression. Adherence to DMT is the cornerstone of MS treatment and management; thus, the discontinuation of therapy is often measured to determine whether MS patients are adherent or nonadherent. By its very nature, nonadherence is difficult to measure empirically. Because most of the current DMTs approved to treat MS must be injected, adherence to MS DMTs is inevitably linked to the problems patients face when self-administering injections. Although it is important to remember that this consideration introduces an additional confounding factor while attempting to gauge the prevalence of nonadherence, the information from various studies suggests that there is a lower percentage of patients who are nonadherent, at least during the first few years of therapy.
A 2008 review of the literature noted that approximately 60% to 76% of patients with MS adhere to treatment with interferon (IFN)-[beta] or glatiramer acetate for 2 to 5 years (Costello et al., 2008). Most of those who discontinue treatment do so during the first 2 years of therapy, as demonstrated by Rio et al. (2005) in a study of 632 patients followed for a mean of 4 years. Of 107 patients who stopped IFN-[beta] or glatiramer acetate during follow-up, 49% did so within 2 years of treatment initiation (Rio et al., 2005).
The Global Adherence Project evaluation of 2,646 patients at 179 sites in 22 countries who had been on their current therapy for at least 6 months (median duration of treatment was 32 months) reported a 25.3% rate of nonadherence to approved DMTs for relapsing-remitting MS (RRMS; Devonshire et al., 2006). Nonadherent patients will obviously not reap all the benefits associated with DMTs and are more likely to be affected by certain factors that can impact adherence, which will be discussed in greater detail in the following section.
Factors Affecting Adherence
In this article, factors affecting adherence that have been identified in the MS literature are reviewed. The factors that have the greatest impact are associated with self-injection and the side effects associated with the DMTs (e.g., injection-site reactions, pain, bruising, lipoatrophy, flu-like symptoms) as well as cognitive impairment and self-efficacy. Other factors, such as patients' level of trust in their healthcare providers, lifestyle and economic stability, family support, and the presence of depression were also identified as barriers to adherence during a recent summit on MS treatment adherence. Although the evidence that supports the impact these factors have on adherence is mainly anecdotal in nature, these observations from practice and patient experiences still serve to educate clinicians about MS patient care. (For more information on these additional adherence factors, please see the accompanying article in this supplement by Saunders et al.).
Clinical studies conducted during the past several years have consistently found that self-efficacy is a strong predictor of treatment adherence (Fraser et al., 2004). The term self-efficacy can be defined as an individual's judgment of his or her ability to organize and implement a course of action necessary to accomplish a task (Fraser & Polito, 2007; Bandura, 1986). Self-efficacy can be further applied to MS patients on DMTs to include an individual's ability to initiate coping behaviors to overcome an abhorrent task (to begin injections), to persist in that behavior because they believe they can accomplish it (continue to inject despite the obstacles), and to set goals to determine how long they will continue said behavior (institute strategies to inject themselves indefinitely; Bandura, 1977).
A prospective study of 104 patients receiving glatiramer acetate (daily, subcutaneous injection) for MS revealed that scores on the Multiple Sclerosis Self-Efficacy Scale (MSSE) significantly predicted adherence (Fraser et al., 2004). The MSSE was adapted from an arthritis scale but includes several additional items that directly pertain to MS (Rigby, Domenech, Thornton, Tedman, & Young, 2003). It is a patient-rated scale that measures a patient's confidence in his or her ability to manage MS and its symptoms, how a patient reacts to limitations of MS, and how MS impacts life activities. The level of a patient's self-efficacy is directly related to their total ratings on questions related to these factors (Rigby et al., 2003). In this study, MSSE scores measured at the initiation of therapy correctly predicted 98.8% of patients who were adherent at a 6-month follow-up (Fraser et al., 2004). The likelihood of adherence increased with each unit of increase in the total score, indicating greater degrees of self-efficacy (Fraser et al., 2004).
Patients' perceptions and beliefs also affect self-efficacy and adherence. A longitudinal study of 101 patients with RRMS who were self-administering IFN [beta]-1 a found that individuals' pretreatment expectations of self-efficacy significantly increased the likelihood of adherence at 6 months (Mohr, Boudewyn, Likosky, Levine, & Goodkin, 2001). In a prospective, open-label study involving 307 patients beginning therapy with glatiramer acetate, clinical observations showed that a sense of control over the disease throughout treatment correlate with better treatment adherence (Kennedy, 2007). Another study, a telephone survey of 89 patients with MS receiving DMTs, was designed to assess the 4 perceptions of the Health Belief Model: the perceived severity of the disease, the susceptibility of the patient to MS (e.g., the patient's belief that their body will be able to fight MS in the future), the perceived benefits associated with treating the disease, and the perceived obstacles to initiate and persist in those behaviors (Turner, Kivlahan, Sloan, & Haselkorn, 2007). Turner et al. (2007) indicated that perceived benefit of medication use at baseline or the confidence that remaining on their medication will positively affect the MS disease process was the only predictor of adherence at 6 months. Similarly, the pros (e.g., belief that the treatment will slow down the deterioration of their condition and the belief that adherence increases the likelihood of maintaining their faculties) and the cons (e.g., side-effects prevented continuation of injections, belief that the treatment did not work, or the injections were too painful) of treatment were key variables influencing adherence in a study of 530 patients receiving intramuscular IFN [beta]-1a (once weekly injection; Berger, Hudmon, & Liang, 2004).
Some data have suggested that self-efficacy may vary by gender and type of MS. A comparative study found that the mean score on the MSSE function subscale was significantly higher among 432 women than among 124 men (p = .001; Fraser & Polito, 2007). Among patients with RRMS compared with progressive forms of the disease, scores on the MSSE subscales were significantly higher for men with RRMS than for those with progressive MS (p = .05 and p = .000, respectively) as well as for women with RRMS versus women with progressive MS (p = .000 for both subscales) (Fraser & Polito, 2007).
Other work has shed light on other factors affecting adherence, including the effects cognitive problems, injection-site reactions and other adverse events, and disability level may have on adherence. In a recent multicenter, observational, Internet-based assessment of 708 patients, Treadway et al. (2009) found that the rate of nonadherence with DMT therapy (defined as missing 1 or more injections during the preceding 4 weeks) was 39% at the time of the initial survey, 37% at 1 month, and 36% at 2 months. The most common reason for lack of adherence (cited by 58% of those deemed nonadherent) was that the patient simply forgot to administer the medication (Treadway et al., 2009). In the Global Adherence Project analysis, the most common reason for lack of adherence was forgetting to administer the injection, reported by 50.6% of nonadherent patients (Devonshire et al., 2006). Compared with patients who adhered to treatment, nonadherent individuals had significantly greater cognitive impairment according to the Multiple Sclerosis Neuropsychological Screening Questionnaire (p = .0002), more problems with injection-site reactions (p < .01), and lower scores on 7 of 9 dimensions of the Multiple Sclerosis International Quality of Life Questionnaire (p < .05; Devonshire et al., 2006). Analysis revealed that further factors affecting adherence were duration of current DMT (p = .017) and duration of disease (p = .0004). Patients who were on therapy for a shorter period as well as those with a shorter disease duration were more adherent (Devonshire et al., 2006). (For more information on injection-specific issues, such as needle phobia and injection-site reactions, please see the accompanying article by Saunders et al., in this supplement.) In the aforementioned literature review by Costello et al. (2008), adverse events accounted for anywhere from 14% to 51% of treatment discontinuations among patients receiving DMTs. The investigation by Rio et al. (2005) found that the primary predictor of discontinuation of a DMT was greater disability. In addition, Berger et al. (2004) reported that a significant relationship was apparent between the extent of disability and the adherence to therapy.
Because patients with cognitive impairments are less likely to be adherent, it is logical that the most likely reason for nonadherence is forgetting to administer treatment. Also, patients with cognitive impairments might also forget to rotate their injection site, making them more vulnerable to injection-site reactions. Patients with a greater disability or a more progressive form of the disease are more likely to discontinue their treatment, whereas patients with a higher level of self-efficacy feel more confident to adequately manage their disease and are more likely to perceive a benefit in continuing their DMT injections even when obstacles are present. Until better methods can be validated, one of the limitations of studies concerning adherence to DMTs is that healthcare practitioners must rely on self-reported data from patients who may have imperfect recall.
Nursing Interventions to Improve Adherence
Several types of strategies have proved effective for improving adherence to DMTs among patients with MS. Because nurses typically have frequent contact with patients, they are often in an ideal position to establish ongoing relationships and to provide supportive interventions (Ross, 2008). Nurses can provide education and information in areas such as correct techniques for self-administration of DMTs, methods for reducing adverse events associated with injections, and self-care behaviors that can minimize the impact of MS on everyday life (Webb, 2008).
Several studies have examined the effects of motivational telephone counseling by nurses. Patients enrolled in a prospective, open-label study at the beginning of their therapy with glatiramer acetate who received scheduled contacts from MS office nurses combined with support from the Shared Solutions[R] program displayed better treatment adherence at 90 days compared with a group of patients who received only the Shared Solutions support (Kennedy, 2007). In an observational investigation, MS patients receiving IFN [beta]-1b (subcutaneous injection, every other day) were offered education, training, and assistance through a telephone-based nursing initiative that encouraged behaviors such as the use of autoinjectors, rotation of injection sites, and adherence to dosetitration protocols (Schapiro, 2004). Patients received initial telephone counseling from participating nurses, who subsequently followed up with additional telephone calls and/or personal visits to ensure appropriate management of treatment (Schapiro, 2004). Data from more than 10,000 patients enrolled in this program showed that only 0.8% discontinued treatment because of injection-site reactions, 2.1% due to flu-like symptoms, and 1.7% due to perceived lack of efficacy (Schapiro, 2004). The results of this study demonstrate how nursing support can improve adherence, in part by improving patients' experiences with DMTs (Ross, 2008).
In a randomized, controlled trial involving 130 community-dwelling patients with MS, those assigned to a treatment group underwent an initial in-person motivational interview and goal-setting meeting with a research care manager, followed by a series of 5 follow-up telephone counseling sessions over 12 weeks (Bombardier et al., 2008). At study completion, measures of health promotion behaviors (including an assessment of "health responsibility") increased significantly in the treatment group (p < .01) but remained unchanged in controls (Bombardier et al., 2008).
The abovementioned studies conducted on the effectiveness of nurse interventions to promote adherence of DMTs, whether telephone based or in person, consistently show that patients benefit from the extra contact. One reason for their success could be because the patient, once enrolled in the study, was not required to continue to initiate contact, and the healthcare practitioners were proactive. However, one limitation to the study performed by Bombardier et al. (2008) was that the motivational interview fidelity could not be objectively measured, although the therapist was properly trained. More important, most studies were carried out in the short term, with durations of roughly 3 months (Bombardier et al., 2008; Kennedy, 2007), except in the observational program for patients receiving IFN [bet]-1b, which did not specify the quantity and span of time that contact was maintained (Schapiro, 2004). Therefore, it would be interesting to understand whether patients benefit further from more prolonged contact and follow-up or if there is an initial vulnerable period, as suggested by the reports from Costello et al. (2008) and Rio et al. (2005), when patients benefit most from nurse contact.
A large body of evidence has confirmed the risks of nonadherence and benefits of adherence with DMT in patients with MS, and a number of factors have been identified that contribute to a patient's level of adherence (see Table 1). Specific interventions have proved effective in helping patients understand the importance of paying close attention to recommended treatment regimens. Clearly, the unique position of nurses within the community of healthcare providers presents a valuable opportunity for helping patients develop practices and behaviors that will facilitate adherence. Good adherence can improve patients' prospects for reducing or delaying the risk of relapse, preserving cognitive and functional abilities for as long as possible, and experiencing the best possible quality of life.
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Questions or comments about this article may be directed to Christina Caon, MSN NP-C, at firstname.lastname@example.org. She is an assistant director of clinical research at the Multiple Sclerosis Center at Wayne State University School of Medicine, Detroit, MI.
Carol Saunders, RN MSCN, is in private practice in Oceanside, CA.
Jennifer Smrtka, ANP-BC MSCN, is a board certified adult nurse practitioner and an IOMSN certified MS nurse at the Ft. Lauderdale MS Center, Pompano Beach, FL.
Nancy Baxter, Expert Medical Education, Washington, DC.
Jennifer Shoemaker, PhD, Expert Medical Education, Washington, DC
This supplement was supported by a grant from Teva Neuroscience. Expert Medical Education contributed to the editorial refinement of this article and to the production of this supplement. Authors may have accepted honoraria for their supplement contributions.
TABLE 1. Clinical Trial-Identified Factors Affecting Adherence Neuropsychological Depression: has been identified as a barrier to adherence Level of cognitive impairment: Patients with a greater level of cognitive impairment were more likely to be nonadherent (Devonshire et al., 2006) Memory problems: The most common reason for nonadherence cited by patients was that they simply forgot to administer their DMT (Devonshire et al., 2006; Treadway et al., 2009) Self-efficacy: Self-efficacy is a strong predictor of adherence (Fraser et al., 2004) Pretreatment expectations of self-efficacy: Greater self-efficacy before treatment increased the likelihood of adherence 6 months after treatment began (Mohr et al., 2001) Sense of control over the disease: A greater sense of control over MS strongly correlated with adherence (Kennedy, 2007) Disease characteristics Duration of disease: Patients with a shorter disease duration were more likely to be adherent (Devonshire et al., 2006) Duration of current DMT: Patients on therapy for a shorter period were more likely to be adherent (Devonshire et al., 2006) Quality of life Extent of disability: A higher EDSS score (greater disability) was a primary predictor of treatment discontinuation (Rio et al., 2005); patients with a greater level of MS disability were more likely to have discontinued therapy (Berger et al., 2004) Number and extent of adverse events: Adverse events accounted for up to 51% of treatment discontinuation (Costello et al., 2008) Problems with injection-site reactions: More patients who were nonadherent reported problems with injection-site reactions (Devonshire et al., 2006) Scores on quality of life questionnaires: Nonadherent patients had lower scores on the Multiple Sclerosis International Quality of Life Questionnaire (Devonshire et al., 2006) Baseline perceptions Perceived benefit of medication use at baseline: A perceived benefit of medication at baseline or the confidence that staying on therapy will have a positive effect on MS was the only predictor of adherence (Turner et al., 2007) Perceived pros and cons of treatment: Pro scores decreased as patients went through various stages that lead to treatment discontinuation while the con scores increased. (Berger et al., 2004) Pros of treatment continuation: treatment will slow down deterioration; adherence increases the likelihood of maintaining faculties Cons of treatment continuation: side-effects prevent continuation of injections; perception that the treatment did not work; injections too painful
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