Multiple sclerosis (MS) is a disease in which disability progresses for many sufferers despite effective disease-modifying therapies [1,2]. It cannot be cured with current therapies. As a result, the generally accepted goals of treatment for MS sufferers are as follows: improve quality of life (QOL) by relieving symptoms caused by exacerbations and reduce the number of these events; reduce MRI activity; delay the onset of secondary progressive MS; slow or stop the course of disease progression; and minimize treatment-associated adverse events . Although these overall goals are generally accepted, they also may vary substantially from one MS sufferer to another. This article focuses on MS sufferer-related, disease-related, and medication-related factors that should be considered in selection of therapy for persons with relapsing-remitting MS (RRMS). It also considers the importance of education and communication aimed at understanding MS sufferer needs, managing expectations, and establishing treatment goals in concordance with the person with MS; and the potential for this approach to improve adherence to therapy and outcomes.
PATIENT-RELATED FACTORS THAT SHOULD BE CONSIDERED IN SETTING TREATMENT GOALS
A very large number of factors should be considered in tailoring treatment for the person with MS (Fig. 1) . Characteristics that may influence treatment goals and selection of therapy include age, culture, education, duration of disease and degree of disability, desired lifestyle, work requirements, literacy and health literacy, coping skills, treatment history (e.g., inability to tolerate specific agents and/or adhere to self-injection regimens), preferences for route of drug/biologic delivery, degree of family/social support, and risk tolerance/aversion [5,6]. For example, younger and more active MS suffers with important work/family responsibilities may want treatment with the greatest potential to slow disease progression and may be willing to accept increased risk for adverse events to achieve this goal. Older, more sedentary persons with long-standing and slowly progressing disease may be willing to accept treatments with lower efficacy in order to avoid the potential for rare, but potentially serious, adverse events.
Consideration of MS sufferer characteristics listed in the preceding paragraph may influence both the treatment selected and route of administration. For example, oral disease-modifying therapy is now available, and many persons with MS may prefer an oral drug. However, the ultimate choice of route of treatment administration should be a decision shared by the person with MS and his or her healthcare providers  and within national guidelines. For example, those with a high probability of poor adherence with self-treatment may benefit from a therapy delivered at specific visits in a healthcare setting. Conversely, MS sufferers who are more likely to adhere to their therapies may prefer a self-injected or oral medication.
ACHIEVING CONCORDANCE IN MULTIPLE SCLEROSIS TREATMENT
Achieving concordance with the person with MS is an important initial consideration in individualizing treatment for individuals with MS. Concordance is a very different concept from compliance to therapy. Compliance is defined as the extent to which the behavior of the individual being treated matches the prescriber's recommendations. It implies a limited role for the person being treated in selection of therapy and in deciding whether or not to take it . Adherence is defined as the extent to which the behavior of the person being treated matches agreed-upon recommendations from the prescriber. It emphasizes that he or she is free to decide whether to adhere to the neurologist's recommendations and that failure to do so should not be a reason for blame . Concordance is a broader concept that includes the consultation process, in which the neurologist and MS sufferer agree upon therapeutic decisions that incorporate their respective views and patient support for taking of medications [8,9▪]. The differences between the compliance and concordance approaches for prescription and taking of medication are summarized in Table 1[8,10,11].
One of the assumptions underlying a concordance model for prescribing and taking of medications is that the MS sufferer desires involvement in these decisions . Results from surveys of such individuals indicate that this is the case. One survey indicated that about 80% of MS sufferers desire autonomous roles in treatment decisions [12,13]. In another small-scale survey, Paterson et al. assessed MS sufferers’ approaches to everyday self-care decision making. These investigators interviewed 21 persons with type 2 diabetes, HIV/AIDS, or MS who were identified as ‘expert self-care managers’ by their clinicians. Study results indicated that these individuals made decisions based on a large number of disease-specific elements related to timeliness, interpretation of biomarkers, interaction within a social context, the construction of health practices, and available relevant information. The MS sufferers stated that they made numerous self-care decisions every day, and that these decisions were made in view of short-term, intermediate-term, and long-term consequences .
MULTIPLE SCLEROSIS SUFFERERS’ ASSESSMENTS OF DISEASE AND TREATMENT RISKS AND BENEFITS
MS sufferers’ involvement in decisions regarding MS treatment includes making judgments about the impact of the disease and the risks and benefits of treatment. There may be substantial differences between patients’ and neurologists’ perceptions of these issues. In one study, 42 consecutive MS sufferers attending a neurology outpatient clinic completed the SF-36 and EuroQol assessments. A neurologist measured neurological impairment using the Expanded Disability Status Scale and an independent nonclinically qualified assistant administered the disability questionnaire of the Office of Population Censuses and Surveys. Study results indicated that persons with MS and clinicians disagreed on which domains of health status were most important. MS sufferers’ assessments of their physical disability using the physical functioning domain of the SF-36 were highly correlated with the clinicians’ evaluations and the nonclinical measurements. However, none of the measures of physical disability correlated with overall health-related QOL measured with EuroQol. These investigators concluded that persons with MS are less concerned than their clinicians about physical disability in their illness .
Persons with MS are also willing to accept significant risk to achieve their treatment goals, and they may be less risk averse than their neurologists. In one study, 651 MS sufferers chose hypothetical treatments from pairs of alternatives with varying levels of clinical efficacy and associated risks. Study results indicated that delay in years to disability progression was the most important factor in treatment preferences. In return for decreases in relapse rates from 4 to 1 and increases in delay in progression from 3 to 5 years, persons with MS were willing to accept a 0.38% annual risk of death or disability from progressive multifocal leukoencephalopathy (PML), a 0.39% annual risk of death from liver failure, or a 0.48% annual risk of death from leukemia . Another study assessed MS sufferers’ and neurologists’ perceptions of risks associated with MS therapy with natalizumab. This treatment is highly effective, but is associated with a rare, but potentially fatal opportunistic infection, PML [17,18]. In this study, 69 persons with MS receiving treatment with natalizumab and 66 neurologists received an evidence-based informational brochure about the risk of PML and were asked to fill out an evaluation sheet. After reading the information, persons with MS were significantly more likely than neurologists to continue natalizumab treatment and willing to accept higher risks of PML; 49% of neurologists would stop treatment at a PML risk of 2 : 10 000 or higher, whereas only 17% of MS sufferers would do so at that event rate [19▪]. Results from another survey of risk acceptance that included results from 5446 persons with MS in the North American Research Committee on Multiple Sclerosis registry indicated that one-half of the respondents would accept a mortality risk more than 1 in 10 000 for a hypothetical MS cure [20▪▪].
It has also been shown that MS sufferers’ prior experience with treatment significantly influences assessment of risk and benefit. In a cross-sectional study conducted between 2007 and 2009, ambulatory sufferers with RRMS and without significant depression or cognitive impairment and who had been taking an IFN-β or glatiramer acetate were asked to respond to a series of questions during a clinic visit [21▪▪]. They were asked if they would consider switching to a new therapy with mild risk and requiring mild vigilance, a new therapy with significant risk and requiring significant vigilance, a new oral therapy with mild risk and requiring mild vigilance, and a new oral therapy with significant risk and requiring significant vigilance. MS sufferers were divided into groups based on duration of therapy (≤5 years or >5 years), with 100 in each group. Persons with MS in both groups indicated they would favorably consider switching to new therapies that carry a mild risk and require mild vigilance or treatment monitoring, with more than 90% in each group indicating they would consider switching to a new oral therapy with mild risk requiring mild vigilance (Fig. 2). Those with longer disease duration were significantly more likely to switch to a new therapy with significant risk and requiring significant vigilance than MS sufferers with shorter treatment durations. More MS sufferers with longer disease duration (59%) than with shorter disease duration (31%) said they would consider switching to a new oral therapy with significant risk requiring significant vigilance. Persons with MS in both groups (70% for shorter treatment duration and 91% for longer duration) favored a reduction in disability progression over decreased relapses as a 10-year treatment outcome [21▪▪].
All of the results reviewed in this section underscore the importance of developing, validating, and implementing tools to educate persons with MS about risk and to help align their perceptions of risk with those of their neurologists.
HELPING PERSONS WITH MULTIPLE SCLEROSIS MAKE INFORMED TREATMENT DECISIONS
In the concordance model, a major role of the clinician who manages persons with MS is to inform, advise, and work with them as part of a team to decide on a course of therapy that best meets their needs. Morgante et al. have described approaches to helping persons with MS make better decisions about their care. The approaches are as follows:
- Establish a collaborative, trusting relationship.
- Be nonjudgmental (understand the MS sufferer's perspective).
- Explore MS sufferer's health beliefs and values, focusing on ethnic/cultural differences (e.g., ask about previous experiences).
- Assess the MS sufferer's support system (family, employment, finances).
- Identify obstacles to MS sufferer participation in decision making (e.g., cognitive limitations).
- Clarify treatment options by explaining the risks and benefits of each therapy.
- Identify the MS sufferer's priorities.
- Listen to the MS sufferer's concerns.
- Help the person with MS recognize and achieve personal comfort with decision making.
- Advocate for the person with MS if his/her decision goes against the team's consensus.
- Help the MS sufferer implement his/her decision (e.g., navigate insurance hurdles).
- Evaluate the outcome of the decision.
- Realize that decision making is a continuous process.
These investigators noted that newly diagnosed MS sufferers may be compelled to make important and emotionally charged decisions regarding treatment that may be influenced by fears about the future. Clinicians should assess the individual MS sufferer's ability and willingness to participate in the decision-making process and tailor interactions accordingly . It has been suggested that education of persons with MS and shared decision making can result in improved treatment satisfaction, better communication by MS sufferers of their values to clinicians, and earlier recognition of ineffective or harmful therapies . In addition, these approaches may result in risk-averse MS sufferers appropriately initiating immunomodulatory therapy early in the course of the disease .
In counseling individuals about treatment for MS, neurologists need to be aware of their ability to influence MS sufferers’ decisions and the potential impact of changing their opinions. One recent study investigated whether neurologists’ recommendations caused persons with MS to change their treatment selection. This investigation included 101 persons with MS who were presented with a hypothetical choice between two drugs. They selected a medication, and then received a fictitious clinician's recommendation for the alternative choice. They then made a final choice between the two agents. Overall, 26% of the persons with MS followed the advice of their neurologist and thus chose the treatment option that differed from their initial preference. Those who followed their neurologist's advice were less satisfied with their decision than patients who did not .
Engaging the person with MS in decision making regarding his or her MS treatment requires the provision of evidence-based information. This has been defined as information about relevant treatment effects communicated in absolute numbers (as absolute risk reductions and/or numbers needed to treat), preferably with the use of illustrations. Presentation of relative risk reductions should be avoided as these are not intuitively understood by MS sufferers and usually overestimate treatment effects . Although absolute risk data may be more readily comprehended, they are derived from clinical trial data and patients should understand that their individual situation is unique. It has been suggested that evidence-based patient information should also focus on the most relevant outcomes for persons with MS (e.g., relapses) with less attention to surrogate measures (MRI results) . These approaches to presentation of information were implemented in an education program aimed at involving MS sufferers in decisions on relapse management. In this study, 150 persons with RRMS were randomized to a single, 4-h group session on relapse management (intervention group) or a standard information leaflet (control group). The author assumed the group session would increase decision autonomy. The primary outcome measure was the proportion of relapses treated with self-administered oral corticosteroids or no corticosteroids (oral or intravenous therapy) as an indicator of MS sufferer autonomy in treatment decision making. Study results indicated that 78% of persons with MS in the intervention group chose to treat their relapse with oral corticosteroids or no corticosteroids. This was the case for 56% of those treating relapses in the control group. Intravenous corticosteroids were administered on an inpatient or outpatient basis to 22% of MS sufferers in the intervention group vs. 44% of those in the control group. Autonomy of treatment decision making in the intervention group was also reflected by fewer visits and telephone calls to neurologists to gain assistance in managing relapses .
Although provision of evidence-based decision aids has gained wide acceptance, concerns have been raised about delivery of such information to persons evaluating treatments, even in highly simplified formats. It has been noted that more than one-half of adults have significant difficulty understanding or applying probabilistic and mathematical concepts and that at least 22% have only the most basic quantitative skills, such as counting; whereas another 33% can do only simple arithmetic. In addition, people may also be biased in their interpretation of risks. They may give exaggerated importance to small risks or, conversely, exhibit optimism bias and exaggerate the chance that they will be among those who benefit from treatment . All of these concerns underscore the importance of the neurologist-MS sufferer interaction in assessing the risks and benefits of alternative treatments in reaching a concordant decision regarding a therapeutic regimen.
EFFECTS OF CONCORDANCE ON ADHERENCE TO THERAPY AND TREATMENT OUTCOMES
Although much has been written about the potential benefits of a concordance approach to treatment selection in persons with MS, there is as yet relatively little evidence from controlled studies to support this approach. However, studies of individuals with other chronic diseases that require significant decisions regarding treatment have indicated substantial benefits with this model. A study of concordance during decision making regarding HIV treatment switching and stopping in relation to patient health-related outcomes included 217 patients who completed a scale that measured concordance. Concordance was measured between the HIV patients’ and physicians’ opinions regarding the change in treatment. Higher concordance was significantly associated with better QOL, less severe and burdensome symptom experience, lower global distress index scores, fewer symptoms reported, higher CD4 cell count, and significantly greater adherence to treatment . The use of a concordance model has also been shown to be effective for controlling blood pressure in individuals with diabetes. Results from a survey of 212 older persons with hypertension and diabetes who were being treated at a Veterans Administration Medical Center indicated that two communication-related factors had independent associations with blood pressure control as determined by multivariate regression analysis: endorsement of a shared decision-making style and proactive communication with one's clinician about abnormal results of blood pressure self-monitoring. A third factor, clinicians’ use of collaborative communication when setting treatment goals, also affected hypertension via its effects on decision-making style and proactive communication .
Although a concordance approach to decision making has not yet been evaluated in persons being treated for MS, there is evidence that improved communication and education enhances the response to treatment. In one study, 120 newly diagnosed MS sufferers were randomly assigned to diagnosis disclosure (current practice) or current practice with an information aid that consisted of a personal interview with a neurologist using a navigable compact disc and a take-home booklet. The primary composite endpoint was a score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety, treatment adherence, extra contacts/consultations, switching of care center, and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores. Study results indicated that 50% of MS sufferers who received the intervention and 13% of those in the control group achieved the primary endpoint. However, no significant treatment effects were seen on secondary outcomes . A second study assessed the influence of an evidence-based patient aid on the decision to undertake MS immunotherapy in a group of 297 patients. The intervention group received the decision aid and a control group received standard information. The primary outcome measure was the match between the MS sufferer's preferred and actual roles during consultation with the neurologist. A secondary outcome was treatment choice. There were no significant between-group differences for the primary or secondary outcome . It has also been shown that education can alter MS sufferers’ expectations regarding therapy. However, these effects are relatively modest. A study that included 99 persons with MS indicated that, before educational intervention, 57% expressed unrealistically optimistic expectations regarding reduction in attack rate, and 34% expressed unrealistically optimistic expectations regarding improvement in functional status that would result from treatment with IFN-β-1b. Education significantly altered unrealistic expectations, but 33% of the persons with MS maintained overly optimistic expectations regarding reduction in attack rate. Posteducation, unrealistic expectations of improvement in functional status were significantly related to discontinuing therapy within 6 months .
In contrast to the modest benefits of the interventions described in the preceding paragraph, results from other studies have indicated that support from healthcare professionals, which might be considered as a component of the concordance model, is associated with better adherence to MS therapy. Results from a study of 341 persons with RRMS who were being treated with glatiramer acetate indicated that 225 were adherent to treatment and 116 were not adherent. Logistic regression analysis revealed that MS sufferers’ perceptions that the neurologist supported taking medication as prescribed was significantly associated with adherence . Similar results were reported in an evaluation of 199 persons with self-reported progressive forms of MS who were also being treated with glatiramer acetate .
Persons with MS vary across a wide range of parameters and their treatment should be individualized to meet their specific characteristics and needs (see Key Points). Individualized treatment may change over the course of a MS sufferer's disease due to variability of symptoms, changes in relapse frequency, and treatment tolerability. When and how therapy should be escalated or switched should be part of the treatment plan for each person with MS. Optimal treatment regimen and route of administration also may vary across MS sufferers and over the course of their disease.
Decisions regarding whether or not to initiate treatment and the selected regimen should be made in consultation with the MS sufferer. Current approaches to optimizing therapy for persons with MS and other chronic diseases have increasingly focused on the MS sufferer as a partner in medical decision making. Studies reviewed in this article indicate that persons with MS value unbiased communication of clinical evidence to support their decision making; and there is a growing body of evidence that provision of such evidence and a concordance approach to decision making has the potential to increase MS sufferer satisfaction and possibly change behavior. As the number of options for disease-modifying therapy in MS grows, the neurologist–MS sufferer partnership in treatment decisions will become increasingly important.
Conflicts of interest
G.G. has received consulting fees from Bayer-Schering Healthcare, Biogen Idec, Elan, Five Prime Therapeutics, Genzyme, Ironwood, Merck Serono, Novartis, Roche, Sanofi-aventis, Synthon BV, UCB Pharma, and Vertex; fees for non-CME/CE services directly from a commercial interest or their agents (eg, speakers’ bureaus) from Genzyme, Merck Serono, and Novartis; and contracted research support from GW Pharmaceuticals, Merck Serono, Merz, and Novartis. R.R. has no conflict of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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