The impact of adjunctive guanfacine extended release on stimulant adherence in children/adolescents with attention-deficit/hyperactivity disorder.

AIM: To assess stimulant adherence among children/adolescents with attention-deficit/hyperactivity disorder (ADHD) augmenting stimulants with guanfacine extended-release (GXR). PATIENTS & METHODS: Inclusion criteria: 6-17 years, ≥1 ADHD diagnosis, ≥1 long-acting and/or short-acting stimulant with GXR augmentation. Modified medication possession ratio (mMPR; days medication available/days in period, excluding medication holidays) was assessed; mMPR <0.80 nonadherent. Regression models assessed change in mMPR adjusting for demographic and clinical characteristics. RESULTS: Among patients nonadherent to stimulants pre-augmentation (n = 165), unadjusted mean (SD) pre- and post-stimulant mMPRs were 0.68 (0.11) and 0.87 (0.16). Adjusted mean change in mMPR was 0.20 for long-acting versus 0.18 for short-acting stimulants (p = 0.34). CONCLUSION: Among patients nonadherent to stimulants, GXR augmentation was associated with increased stimulant adherence.

Impact of a Step Therapy for Guanfacine Extended-Release on Medication Utilization and Health Care Expenditures Among Individuals Receiving Treatment for ADHD.

BACKGROUND: While step therapy (ST) policies are generally effective at reducing cost through the managed utilization of targeted medications, the clinical implications of ST policies are not clear and may vary across therapeutic areas. Guanfacine extended-release (GXR) is approved by the FDA for the treatment of attention-deficit/hyperactivity disorder (ADHD) as both monotherapy and adjunctive to stimulant treatment. At the introduction of GXR to the market, Humana implemented an ST policy on GXR requiring the documentation of previous treatment, intolerance, or contraindication to generic clonidine or guanfacine. OBJECTIVE: To examine the impact of a GXR ST coverage determination (i.e., approved vs. denied) on medication utilization and health care costs among members of a commercial health plan with an ST policy for GXR.  METHODS: This study was a retrospective cohort study of administrative claims data. Humana commercial members prescribed GXR who had an ST coverage determination review were identified. All members included in this analysis were required to be aged 6-17 years, have a diagnosis of ADHD or be receiving stimulant medication, have an ST coverage determination (index event) between September 1, 2009, and May 30, 2012, and have 6 months of pre- and post-index continuous enrollment. Members were assigned to either the approved or denied group based on the outcome of the ST coverage determination. Medical and pharmacy claims data were used to measure baseline demographic and clinical characteristics and to measure medication utilization and health care costs. Outcomes assessed during follow-up included ADHD medication use, proportion of days covered (PDC) with any ADHD medication treatment, time to first observed post-index ADHD treatment, and all-cause and mental health (MH)-related health care costs. Administrative costs associated with the coverage determination process were also estimated. Bivariate and multivariable adjusted analyses were conducted to compare medication utilization and health care costs between the approved and denied groups. RESULTS: A total of 642 members were included in the analysis (denied group n = 395 [61.5%], approved group n = 247 [38.5%]). The approved and denied groups were similar in terms of baseline demographics, provider characteristics, and baseline MH diagnoses, with the exception of anxiety disorders being more prevalent in the approved group compared with the denied group (18.2% vs. 10.6%, P = 0.006). A denied GXR coverage determination was associated with a greater percentage of members receiving no ADHD treatment post-index (13.9% vs. 3.2%, P less than 0.001), greater mean [SD] number of days between index and first observed post-index ADHD medication claim (44.5 [59.6] vs. 17.6 [33.4], P less than 0.001), and lower mean [SD] PDC with any ADHD medication post-index (0.59 [0.33] vs. 0.75 [0.26], P less than 0.001). These findings remained statistically significant in multivariable regression models. Unadjusted pre-index median total health care costs and MH-related costs were greater among the approved group compared with the denied group (total health care: $1,582 vs. $1,465, P = 0.033; MH-related: $993 vs. $981, P = 0.020). Likewise, post-index median total health care and MH-related costs were greater among the approved group compared with the denied group (total: $2,056 vs. $1,420, P less than 0.001; MH-related: $1,543 vs. $946, P less than 0.001). After adjustment for potentially confounding covariates including pre-index costs, there were no statistically significant differences between the approved and denied groups in all-cause total health care (P = 0.393) or MH-related health care costs (P = 0.054).  CONCLUSIONS: The current study found that GXR coverage denial was associated with lower rate of ADHD medication utilization, greater delay in receiving ADHD medication, and lower PDC with ADHD medication. There were no differences observed between the approved and denied group in terms of all-cause total health care or MH-related total health care costs after controlling for potentially confounding variables. Prior to implementation in the ADHD therapeutic area and others, payers should consider the potentially unintended consequences of ST policies, including delay in treatment and undertreatment.

Cost effectiveness of guanfacine extended-release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder: application of a matching-adjusted indirect comparison.

BACKGROUND: About 7% of children and adolescents are diagnosed with attention-deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are intolerant of or do not have an optimal response to stimulants often use non-stimulants as alternative therapies. Guanfacine extended-release (GXR) and atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug Administration for once-daily use in the treatment of children and adolescents with ADHD in the US. ATX has been on the market since 2002 while GXR was recently approved in 2009. To date, there is no comparative effectiveness or cost-effectiveness study comparing the two drugs. OBJECTIVES: The aim of this study was to assess the cost effectiveness of GXR versus ATX for the treatment of ADHD in children and adolescents, using the comparative efficacy results from a matching-adjusted indirect comparison (MAIC). METHODS: The MAIC method was used to compare the efficacy between GXR (target dose and lower doses) and ATX (target dose) in the absence of head-to-head clinical trials. Individual patients in the GXR trials were weighted such that the summary baseline characteristics and the efficacy of the placebo arm of the GXR trials matched exactly with those from published ATX trials. After weighting, the efficacy (i.e. change in the ADHD rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared between each GXR dosing group and the ATX group. The results from the MAIC analyses were used to populate a 1-year Markov model that is used to compare the cost effectiveness of GXR versus ATX from a US third-party payer perspective. Effectiveness outcomes for each treatment group were estimated as the proportion of responders, defined as patients with ≥25% reduction in ADHD-RS-IV total score from baseline, and average quality-adjusted life years (QALYs). Utilities associated with response/non-response and disutilities due to adverse events were applied in the model. Costs included drug and medical service costs and were inflated to 2011 US dollars ($US). Incremental cost/QALY and incremental cost/responder were estimated. Univariate sensitivity analyses were conducted by varying all model parameters, including costs, utilities, and response rate. RESULTS: The target dose of GXR was 0.12 mg/kg/day. In match-adjusted populations with balanced baseline characteristics, patients receiving GXR at the dose of 0.09-0.12(p = 0.0016) [DOSAGE ERROR CORRECTED] and 0.075-0.09 mg/kg/day (p = 0.0248) had better efficacy, while those receiving GXR at the dose of 0.046-0.075 mg/kg/day had comparable efficacy (p = 0.0699), compared with patients receiving ATX at the target dose of 1.2 mg/kg/day. In the base case of the cost-effectiveness analysis (CEA), GXR had incremental cost-effectiveness ratios of $US10 637/QALY and $US853/responder, compared with ATX (incremental costs: $US74; incremental effectiveness: 0.007 QALYs and 86 responders per 1000 patients treated). Results of all univariate sensitivity analyses showed that the model results were robust to changes in model inputs. CONCLUSIONS: To our knowledge, this is the first application of the novel comparative efficacy method of MAIC to a CEA model. The MAIC results indicate that GXR (0.075-0.12 mg/kg/day) was more effective than ATX (1.2 mg/kg/day) in the trial population. The CEA results indicate that GXR is cost effective compared with ATX for the treatment of ADHD in children and adolescents.

Cost effectiveness of guanfacine extended release as an adjunctive therapy to a stimulant compared with stimulant monotherapy for the treatment of attention-deficit hyperactivity disorder in children and adolescents.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood, affecting 3-7% of school-age children in the US and imposing substantial economic burden. Stimulants are considered first-line pharmacological treatment and are the most prescribed treatment for ADHD. However, approximately 30% of children with ADHD do not have an optimal response to a single stimulant and may require adjunctive therapy. OBJECTIVE: Our objective was to conduct a cost-effectiveness analysis (CEA) of adding a non-stimulant, guanfacine extended release (GXR), to stimulants versus maintaining existing stimulant monotherapy in the treatment of ADHD in children and adolescents with suboptimal response to stimulant monotherapy. METHODS: A 1-year Markov model was developed to estimate costs and effectiveness from a US third-party payer perspective. Effectiveness was measured by the QALY. The model assumed that patients transitioned among four health states (normal, mild, moderate and severe), defined by the Clinical Global Impression-Severity (CGI-S) scale. Transition probabilities were estimated in an ordered logit model using patient-level data from a multicentre, 9-week, double-blind, placebo-controlled, dose-optimization study, where subjects (n = 461) continued their stable morning stimulant and were randomized to GXR administered in the morning, GXR administered in the evening, or placebo. The model assumed that patients in moderate/severe health states after week 8 would discontinue ADHD treatment and remain in that state for the rest of the study period. Direct costs included drug wholesale acquisition costs and health state costs, all in $US, year 2010 values. Utility associated with each health state was obtained from the literature and disutilities associated with adverse events were applied for the first 4 weeks. One-way sensitivity analyses and probabilistic sensitivity analysis (PSA) were conducted by varying costs, utilities, adverse-event duration, and transition probabilities. RESULTS: Compared with maintaining existing stimulant monotherapy, adding GXR to existing stimulant monotherapy was associated with an incremental drug cost of $US1016 but a lower medical cost of $US124, resulting in a total incremental cost of $US892 at 1 year. The addition of GXR to stimulants led to an incremental QALY of 0.03 and an incremental cost-effectiveness ratio (ICER) of $US31,660/QALY. In one-way sensitivity analysis, ICER values ranged from $US19,723, when 100% of patients were assumed to be severe in their initial health state, to $US46,631, when the last observed states from the clinical trial were carried forward to the end of the 1-year analysis period. PSA demonstrated a 94.6% likelihood that the ICER falls below $US50,000/QALY. CONCLUSIONS: The impairment associated with residual ADHD symptoms after stimulant therapy is becoming increasingly recognized. This is the first analysis of the cost effectiveness of stimulants combined with an adjunctive medication. This study suggests that the adjunctive therapy of GXR with stimulants is a cost-effective treatment based on a willingness-to-pay threshold of $US50,000/QALY. This may address an unmet need among patients with suboptimal response to stimulant monotherapy.