The Cost Effectiveness of Lisdexamfetamine Dimesylate for the Treatment of Binge Eating Disorder in the USA

Binge eating disorder (BED) is a chronic psychiatric disorder, characterized by recurrent episodes of compulsive overeating (binge eating episodes) during which patients consume larger amounts of food than normal, experience the lack of control and which are not followed by compensatory behaviors (e.g. self-induced vomiting, diuretic or diet pills abuse, or intense exercising) [1]. Binge eating is often rooted in poor body image, use of food to deal with stress, low self-esteem and dysfunctional thoughts [1]. BED appears to affect a broader spectrum of the population than anorexia nervosa and bulimia nervosa; the lifetime prevalence of BED is about 1–2 % [2, 3, 4, 5, 6]. With the association of BED and obesity, this disorder becomes a clinically significant disorder that presents both medical and psychiatric issues that impair the health-related quality of life (HRQoL) and increase healthcare utilization [2, 7].

BED has a large, under-served patient population due to the absence of satisfactory medical treatments. This is also supported by the fact that currently only a minority of patients receive a specific treatment for BED [4, 7, 8]. Therapies are intended to treat and control the symptoms of BED, such as binge eating, overweight, and the disorder-specific psychopathology [9]. Treatment options of BED include pharmacological and non-pharmacological therapies applied alone or in combination. Studies support the effectiveness of non-pharmacological interventions (i.e. cognitive behavioral therapy, interpersonal psychotherapy, dialectical behavior therapy, and behavioral weight-loss therapy) in the treatment of BED [10]. Nevertheless, non-pharmacological interventions have demonstrated only a minimal impact on weight control in the long term [10], and may not be suitable for people who have more complex mental health needs, or learning difficulties. While some limited scientific evidence suggests that selective serotonin reuptake inhibitors (e.g. fluoxetine) [11, 12, 13], serotonin–norepinephrine reuptake inhibitors (e.g. duloxetine) [14], and antiepileptic drugs (e.g. topiramate) [15, 16] have an advantage over placebo for achieving reduced binge eating frequency and decreased body weight, none of these drugs is approved for the treatment of BED [17].

Lisdexamfetamine dimesylate (LDX, Vyvanse^®) 50 and 70 mg is a novel pharmacotherapy that was recently approved by the United States Food and Drug Administration (US FDA) for the treatment of adults with BED. LDX demonstrated efficacy versus placebo in decreasing binge eating days per week from baseline in two randomized, placebo-controlled, parallel-group, multicenter studies, with the same design and methods (i.e. SPD489-343 and SPD489-344) [18]. LDX also showed improvement in binge eating-related secondary endpoints (e.g. binge eating episodes per week, the global impressions of BED improvement, 4-week cessation from binge eating, change in body weight, obsessive/compulsive binge eating symptoms, and triglycerides) [18]. LDX may be a first-line drug therapy option in BED with or without psychotherapy, as determined by physicians.

Under budgetary constraints, cost-effectiveness analyses have increasingly been used as a tool to select health interventions for public financing. Cost-effectiveness analysis permits comparing different treatment options upon these health benefits and economic value [19]. The objective of this study was to assess the cost effectiveness of LDX compared with no pharmacotherapy (NPT, placebo) for the treatment of adult BED patients from a US healthcare payer perspective.

A decision-analytic Markov cohort model (Microsoft Excel 2010) was designed using a 52-week time horizon to estimate the cost effectiveness of LDX compared with NPT. NPT was represented by placebo in terms of effect. The model was designed from the healthcare payer perspective in the USA, thus only health outcomes [i.e. quality-adjusted life years (QALYs)] and direct medical costs were considered in the analysis. Because of the 52-week time horizon, no discounting was performed. The choice of this relatively short time horizon can be justified by the lack of long-term data (LDX pivotal trials in BED were 12-week long [18]) that could be used to inform the economic model in terms of the long-term benefits of LDX therapy in BED.

The Markov model consisted of seven mutually exclusive health states as presented in Fig. 1 with the duration of each cycle being 1 week. Health states were defined in accordance with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria [1]. The 1-week cycle length was chosen because this time period was appropriate to determine DSM-5 binge eating behavior severity states [1]. Mortality was not included in this analysis as the time horizon of the model was 52 weeks and there were no data available on the effect of LDX on mortality in BED patients.

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The choice of using NPT (placebo) as comparator is supported by the facts that (1) no comparative data with other intervention exist and there is no ongoing LDX clinical trial with active comparator, (2) no other drug therapy is approved for the treatment of BED in the USA, and (3) currently only a minority of BED patients receive pharmacological and/or non-pharmacological treatment specifically for their eating disorder [2].

There are no real-world data on the expected duration of LDX therapy in BED. In the analysis, the treatment length was set to 12 weeks with steady relapse after treatment was completed, which was chosen for the following reasons: (1) in the LDX pivotal clinical trials the treatment period was 12 weeks long [18]; and (2) when conducting this analysis no efficacy data for long-term treatment existed and there were no data on recurrence and remission of BED after the discontinuation of LDX therapy.

Transition probabilities between Markov health states were calculated based on individual binge eating behavior severity data (i.e. number of binge eating episodes in the last week) from the pivotal clinical trials [18] for both LDX and NPT arms. Online Resource 1 depicts the transition probability matrices for LDX and NPT arms. The model assumed steady relapse after LDX treatment was completed, thus after the 12th cycle transition probabilities were equal in both arms. Discontinuation due to adverse events (AEs) on the LDX arm was considered in the analysis.

Treatment-emergent AEs related to LDX therapy occurring in more than 5 % of subjects in the pivotal clinical trials [18] were considered in the analysis, i.e. dry mouth, insomnia, headache, nausea and decreased appetite (weekly incidence rates of AEs were 0.64, 0.29, 0.13, 0.18, and 0.13 %, respectively). Costs of AEs were assumed to be resolved during the cycle in which the AE took place. Costs of AEs per week associated with LDX therapy were calculated by multiplying the weekly incidence of AEs with cost of family doctor visit (US$154.62) [22]. Dis-utilities linked to AEs were considered during the utility estimation of health states [18]. Patients who discontinued therapy were assumed to generate the mean utility and mean cost per week of patients on NPT arm (0.0175 QALY per week, US$132.05 per week).

By systematically changing the base-case estimates [i.e. each variable by ±10 % (utility values were maximized at 1.00, thus utility of non-symptomatic BED health state could be increased only by 5.35 %; to be able to compare the effect of uncertainty related to utility variables ±5.35 % were applied for all utility variables)], a series of one-way deterministic sensitivity analyses (DSA) was programmed and run through the model to find the most sensitive parameters [23]. Probabilistic sensitivity analysis (PSA) was also performed to account for the simultaneous effect of uncertainty relating to model parameter values; 10,000 model iterations were run by using Monte Carlo simulation. In the PSA, transition probabilities, utilities and AE incidence rates were sampled from beta distributions, and healthcare utilization frequencies and costs were sampled from gamma distributions. Parameters for sampling distributions were derived from point estimates and standard errors for each variable [24].

Quality-control procedures were performed by a modeler not involved in the model development according to a pre-specified test plan and included both programming validation and the verification of all input data with their original sources. In addition, a series of diagnostic tests were conducted to confirm that the model was correctly applying all formulas.

This is the first study to examine the cost effectiveness of LDX compared to NPT (placebo) for the treatment of adults with BED in the USA. Results of this Markov model showed that BED patients treated with LDX for 12 weeks had better clinical outcomes [18] at slightly increased costs. The overall ICER was US$27,618 per QALY suggesting that LDX may be a cost-effective option compared with NPT in adult patients with BED considering a willingness to pay threshold of US$50,000. These findings can support healthcare payers regarding the efficient allocation of health resources, as cost-effective interventions are highly desirable in improving healthcare system efficiency.

Based on the results of the conducted DSA, the most sensitive input parameter was the utility value of ‘non-symptomatic BED’ health state; the influence of other model parameters was less marked. A cost-effectiveness acceptability curve was also calculated, showing the probability of cost effectiveness of LDX given varying willingness to pay for a QALY. At the commonly used willingness to pay threshold (US$50,000) in the USA [26], compared with NPT, LDX had an 82 % chance of being cost effective in BED.

LDX is a novel treatment for BED and when conducting this analysis no long-term efficacy data to estimate its potential long-term benefits in BED, including long-term reduction in body weight and the health consequences of weight reduction (e.g. decrease in the prevalence and the severity of diabetes, hypertension, hypercholesterolemia, heart failure, ischemic heart disease) were available, that may affect the cost effectiveness of LDX in the long run.

Evidence suggests that the budget impact of introducing LDX for the treatment of BED would be modest in the USA [26]. In a budget-impact analysis, the total direct budgetary cost of treating BED within the adult US population without LDX was estimated to be US$241,699,596 over one year [26]. If LDX were to treat 17.5 % of patients diagnosed with BED, then the expected total annual budget would increase by US$1,069,080 in the USA, which would be primarily due to the drug cost of LDX, as there would be expected healthcare utilization costs savings of US$2,257,096 [26].

Treatment of BED with LDX showed an increase in QALYs at an acceptable cost and is considered cost effective at the commonly used willingness-to-pay threshold (US$50,000) in the USA. Based on the available evidence the current model focused on short-term benefits only; however, additional scientific evidence supporting long-term benefits may further validate the health economic results.