Abstract and Introduction
Disease-modifying therapies can positively influence the progression of multiple sclerosis, but how many patients continue to take their medications? A new study shows that the majority of patients with multiple sclerosis stop treatment. Research should focus on ways to improve adherence to disease-modifying therapies.
Several disease-modifying therapies (DMTs) have been shown to reduce disease exacerbations, inhibit the formation of brain lesions, and/or slow disease progression in relapsing–remitting multiple sclerosis (MS). Despite moderate success in the development of these efficacious drug therapies, a recent study by Wong et al. highlights a major problem with maintaining long-term treatment in this condition—patient adherence is poor and many patients stop treatment altogether.
Using a Canadian public health database, Wong and colleagues retrospectively identified 682 patients with MS who had initiated treatment with intramuscular interferon (IFN)-β1a, subcutaneous IFN-β1b, IFN-β1b, or glatiramer acetate. Generally consistent with other studies examining DMT persistence, approximately half of patients with MS discontinued their DMT within 2 years of drug initiation. Poor treatment persistence was independent of drug costs and rarely related to patients switching to another class of DMT (switching between DMT types occurred in only 3.4–6.5% of patients).
The above results are not specific to MS; poor treatment adherence is common among patients with many types of chronic disease. Nonetheless, patients with MS may be at especially high risk of poor long-term adherence for several reasons. DMTs do not typically reduce chronic symptoms; thus, patients do not experience any improvement in their daily activities while on medication. In fact, in some cases, patients experience adverse symptoms from the medications themselves and may, therefore, endure a reduction in quality of life while on therapy. Additionally, during periods of remission, patients with MS might become complacent and not feel the need to take their medication; conversely, they might question efficacy and discontinue their medication when doing poorly. Cognitive and emotional difficulties, which are common in patients with MS, can also impede treatment adherence. Despite high rates of treatment discontinuation, few large-scale studies have examined the myriad factors that may contribute to poor treatment adherence in MS.
Adherence can be defined as a patient's ability to accurately follow a prescribed treatment regimen. Nonadherence in MS can take many forms, including refusing to initiate recommended therapies, discontinuing therapies prematurely, or deviating from prescribed medication regimens. As in the study by Wong and co-workers, large-scale studies that have examined treatment adherence in MS have typically focused exclusively on measures of treatment discontinuation. Findings from these studies indicate that 30–70% of patients with MS prematurely discontinue or switch their DMTs.[5,6] However, these studies frequently rely on pharmacy databases, claims records, or retrospective patient self-reports. Consequently, they do not fully capture the extent of adherence difficulties in MS. Studies focused on patients who continue to take their medication have also identified irregular or inconsistent dosing. A 2010 prospective study using objective methods of adherence measurement found that approximately one-fifth of patients with MS miss over 20% of their scheduled doses. Moreover, studies examining irregular dosing patterns probably underestimate poor adherence due to inflated self-reports of adherence and study-related selection biases (patients who know they are nonadherent are unlikely to participate in an adherence study). If we combine all those groups of patients not taking DMTs adequately—patients who refuse to initiate therapy, patients who discontinue therapy and patients who miss a large proportion of their regular medication—a preponderance of evidence suggests that a clear majority of patients with MS receive inadequate treatment.
In the Wong et al. study, DMT discontinuation was consistent across classes of DMTs. Each of the first-line FDA-approved DMTs requires regular self-injection. A substantial number of patients might discontinue or avoid the initiation of these DMTs because of injection anxiety and discomfort. Several oral therapies have shown promise in clinical trials; one agent (fingolimod) recently received FDA approval and others are expected to follow soon. With the eventual adoption of oral medications as first-line therapies for MS, it is possible that patients may initiate DMT treatments more frequently and earlier. However, oral medications are unlikely to eradicate adherence difficulties in MS. Poor adherence is common in most chronic diseases, regardless of treatment modality, and other issues, such as adverse medication effects, lack of immediate response, and complacency, may still create barriers to good adherence.
The WHO has suggested that improved treatment adherence would have a larger effect on society and health than most major therapeutic advances. Results from Wong et al. reinforce an urgent need to better understand and treat poor adherence in MS. Only a few studies have examined ways to improve adherence to DMTs in MS. In 2005, Berger and colleagues conducted a randomized clinical trial with the aim of increasing medication persistence among a group of patients with MS who had recently initiated treatment with a DMT. In this study, only 1.2% of patients receiving a telephone-based counseling service discontinued their DMT compared with nearly 9% of patients receiving standard care. Another study showed that treatment of depression in patients with MS improved DMT treatment persistence. Several papers point to theoretically important variables to consider when encouraging treatment adherence in MS. Treatment adherence might be increased with patient education, open patient–physician communication, and the mitigation of health-care barriers. Additional research is also needed to better identify emotional, clinical and social factors that contribute to poor adherence in MS. Identifying the relative importance of these factors may lead to the development of effective, specific interventions that reduce adherence problems in MS.
In summary, despite the development of moderately successful pharmacological treatments to reduce disease activity in relapsing–remitting MS, evidence from Wong et al. suggests that approximately half of patients with MS discontinue their DMTs. In combination with adherence research that demonstrates difficulty with treatment initiation and inadequate dosing among long-term users, the majority of patients may well be receiving insufficient medication to reduce or delay the progression of MS. Existing evidence indicates that improved medication adherence could have a major effect on disease progression and overall health in patients with MS. Nonetheless, few studies have examined the underlying factors that contribute to poor adherence in MS, and even fewer researchers have conducted clinical trials that aim to improve adherence. The countless hours and money that have been spent creating and studying efficacious DMTs for MS are wasted if the patients do not take these medications.
More research is needed to improve our ability to understand the underlying barriers to continued therapy and to help patients maintain good treatment adherence in MS. In particular, studies must first help to identify the most common factors associated with nonadherence (such as adverse effects of medications, emotional changes, cognitive problems, or communication patterns), and then evaluate targeted, practical interventions, probably including education or counseling strategies tailored to the individual, to change or reduce the effects of these factors.
S. G. Lynch declares associations with the following companies: Actelion, Artielle Immunotherapeutics, Bayer, Biogen Idec, Eli Lilly, Genentech, Genzyme, Merck Serono, Novartis, ONO Pharma, Teva Pharmaceutical Industries, UCB Pharma. See the article online for full details of the relationships. J. M. Bruce declares no competing interests.
Nat Rev Neurol. 2011;7:421-422. © 2011 Nature Publishing Group