Health state utilities associated with hyperphagia: Data for use in cost-utility models.

Objective: Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods: Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample. Results: In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were -0.08 (0.10) for mild, -0.28 (0.30) for moderate, and -0.77 (0.58) for severe hyperphagia. Conclusions: These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.

Effects of variations in access to care for children with atopic dermatitis.

BACKGROUND: An estimated 50% of children in the US are Medicaid-insured. Some of these patients have poor health literacy and limited access to medications and specialty care. These factors affect treatment utilization for pediatric patients with atopic dermatitis (AD), the most common inflammatory skin disease in children. This study assesses and compares treatment patterns and healthcare resource utilization (HCRU) between large cohorts of Medicaid and commercially insured children with AD. METHODS: Pediatric patients with AD were identified from 2 large US healthcare claims databases (2011-2016). Included patients had continuous health plan eligibility for ≥6 months before and ≥12 months after the first AD diagnosis (index date). Patients with an autoimmune disease diagnosis within 6 months of the index date were excluded. Treatment patterns and all-cause and AD-related HCRU during the observation period were compared between commercially and Medicaid-insured children. RESULTS: A minority of children were evaluated by a dermatology or allergy/immunology specialist. Several significant differences were observed between commercially and Medicaid-insured children with AD. Disparities detected for Medicaid-insured children included: comparatively fewer received specialist care, emergency department and urgent care center utilization was higher, a greater proportion had asthma and non-atopic morbidities, high- potency topical corticosteroids and calcineurin inhibitors were less often prescribed, and prescriptions for antihistamines were more than three times higher, despite similar rates of comorbid asthma and allergies among antihistamine users. Treatment patterns also varied substantially across physician specialties. CONCLUSIONS: Results suggest barriers in accessing specialty care for all children with AD and significant differences in management between commercially and Medicaid-insured children. These disparities in treatment and access to specialty care may contribute to poor AD control, especially in Medicaid-insured patients.

Treatment patterns of pediatric patients with atopic dermatitis: A claims data analysis.

BACKGROUND: Real-world evidence on treatment patterns of pediatric patients with atopic dermatitis (AD) is sparse. OBJECTIVE: To assess current treatment patterns in pediatric AD patients. METHODS: Retrospective observational analysis of commercial insurance and Medicaid administrative claims data (January 2011-December 2016) for pediatric AD patients, stratified by age and provider type. RESULTS: The analytic sample comprised 607,258 pediatric AD patients. Median observation period was 30.3 months. Overall, 78.6% were prescribed ≥1 AD medication; 86.7% were prescribed topical corticosteroids, and 5.4% were prescribed a calcineurin inhibitor. Systemic corticosteroids (SCSs) were prescribed for 24.4% of patients, 51.8% of whom did not have asthma or allergic comorbidities. Of the 46.6% prescribed an antihistamine and 16.2% prescribed montelukast, 62.0% and 41.3%, respectively, did not have asthma or allergic comorbidities. Systemic immunosuppressants were rarely prescribed (<0.5%). Higher potency topical corticosteroid and SCS use increased with age. Treatment patterns varied by provider type; specialists were more likely to prescribe higher potency topicals and/or systemics, regardless of patient age. A minority of patients were treated by or referred to a specialist. LIMITATIONS: Identification of AD patients relied on billing diagnoses; the disease severity was proxied by the treatment prescribed. CONCLUSION: Results indicate that SCSs, despite known risks, and other medications with disproven efficacy in AD are frequently prescribed, suggesting a need for safer and more effective alternatives.

Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately to severely active rheumatoid arthritis: an analysis of incremental cost per effectively treated patient.

PURPOSE: Treatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment. PATIENTS AND METHODS: Short-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire - Disability Index score and via published algorithms. RESULTS: For sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses. CONCLUSION: Sarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.

Real-world utilization patterns of systemic immunosuppressants among US adult patients with atopic dermatitis.

At the time of this study, prior to the introduction of biologics in the US, systemic therapies used for the treatment of moderate-to-severe atopic dermatitis included off-label immunosuppressants and corticosteroids. Immunosuppressant therapy is associated with a substantial risk of side-effects, therefore needing clinical monitoring, and is likely to incur a significant healthcare burden for patients and payers. This retrospective cohort study based on claims data measured immunosuppressant use and its associated burden among US adult patients with atopic dermatitis covered under commercial or Medicare Supplemental insurance from January 01, 2010, to September 30, 2015. Overall, based on age, gender, region, and index year, 4201 control patients with atopic dermatitis without immunosuppressant use were matched with 4204 patients treated with immunosuppressants. The majority (68.5%) of patients using immunosuppressants were non-persistent with immunosuppressant treatment during the 12-month follow-up period after a mean (standard deviation) of 88.1 (70.7) days of immunosuppressant use; 72.3% required systemic steroid rescue treatment. Immunosuppressant users had higher incidence of immunosuppressant-related clinical events than controls; in addition, a larger proportion of immunosuppressant users versus controls developed cancer (0.28% vs 0.14%, respectively; P < 0.0001). Healthcare utilization and costs associated with clinical events and monitoring were also higher for immunosuppressant users compared with controls (total costs, $9516 vs $1630, respectively; P < 0.0001; monitoring costs, $363 vs $54, respectively; P < 0.0001). This study revealed that patients treated with systemic immunosuppressants often require systemic steroids or changes to treatment. The increase in immunosuppressant-related clinical events, including the need for increased monitoring with immunosuppressant treatment, compared with controls demonstrates a substantial treatment burden and highlights the unmet need for more effective long-term therapies for atopic dermatitis with improved safety profiles and reduced monitoring requirements.

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

OBJECTIVE: The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). METHODS: A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. RESULTS: Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. CONCLUSIONS: The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

Clinical and economic consequences of statin intolerance in the United States: Results from an integrated health system.

BACKGROUND: Although statins are considered safe and effective, they have been associated with statin intolerance (SI) in clinical and observational studies. OBJECTIVE: The objective of this study was to describe the clinical and economic consequences of SI through comparison of an SI cohort of patients with matched controls. METHODS: This study used data extracted from an integrated health system's electronic health records from 2008 to 2014. Adults with SI were matched to controls using a propensity score. Patients were hierarchically classified into 6 mutually exclusive cardiovascular (CV)-risk categories: recent acute coronary syndrome (ACS; ≤12 months preindex), coronary heart disease, ischemic stroke, peripheral artery disease, diabetes, or primary prevention. The study endpoints, low-density lipoprotein cholesterol (LDL-C) goal attainment, medical costs, and time to first CV event were compared using conditional logistic regression, generalized linear, and Cox proportional hazards models, respectively. RESULTS: Patients with SI (n = 5190) were matched with controls (n = 15,570). Patients with SI incurred higher medical costs and were less likely to reach LDL-C goals than controls. Patients with SI were at higher risk for revascularization procedures in all CV risk categories except ACS, and those in the diabetes risk category were at higher risk for any CV event. There was a lower risk of all-cause death among patients with SI. CONCLUSIONS: Patients with SI were less likely to reach LDL-C goals, incurred higher health care costs, and experienced a higher risk for nonfatal CV events than patients without SI. Alternative management strategies are needed to better treat high CV risk patients.

Development and Content Validity of the Statin Experience Assessment Questionnaire (SEAQ)©.

INTRODUCTION: The National Lipid Association Statin Intolerance (SI) Panel recognized the need for better understanding of the patient SI experience. OBJECTIVE: The objective of this research was to develop a patient-reported outcome (PRO) questionnaire to assess a patient's experience with SI. METHODS: Questionnaire development was informed via a series of research activities: literature review, concept elicitation, item generation, and content evaluation. Following the literature review and concept elicitation, a draft questionnaire was constructed and subsequently modified based on feedback from therapeutic area experts and patients via cognitive debriefing interviews. RESULTS: Muscle-related symptoms were the most commonly reported symptoms associated with SI in the literature review (35 of 41 articles reviewed [85%]) and in semi-structured interviews with experts (n = 5 [100%]) and patients (n = 17 of 20 [85.0%]). Physical and other impacts of SI symptoms on daily activities were also frequently reported. A 17-item draft questionnaire was created, and cognitive debriefing with experts (n = 5) and patients (n = 15) was conducted. Overall, the items, response options, and instructions were comprehensible and positively reviewed; minor changes resulted in the 15-item Statin Experience Assessment Questionnaire (SEAQ)©. Using a 30-day recall period, the SEAQ© assesses the severity and impact of six SI symptoms (muscle ache, muscle pain, muscle cramps, muscle weakness, tiredness, and joint pain) on an 11-point numeric scale. Statin discontinuation and likelihood of discontinuation due to symptoms are assessed and scored on a yes/no and five-point verbal response scale, respectively. CONCLUSION: The SEAQ

Patterns of Statin Use in a Real-World Population of Patients at High Cardiovascular Risk.

BACKGROUND: Widespread use of statins has improved hypercholesterolemia management, yet a significant proportion of patients remain at risk for cardiovascular (CV) events. Analyses of treatment patterns reveal inadequate intensity and duration of statin therapy among patients with hypercholesterolemia, and little is known about real-world statin use, specifically in subgroups of patients at high risk for CV events. OBJECTIVE: To examine patterns of statin use and outcomes among patients with high-risk features who newly initiated statin monotherapy. METHODS: Adult patients (aged > 18 years) at high CV risk who received > 1 prescription for statin monotherapy and who had not received lipid-modifying therapy during the previous 12 months were identified from the Truven MarketScan Commercial and Medicare Supplemental databases (from January 2007 to June 2013). Patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes were hierarchically classified into 5 mutually exclusive CV risk categories (listed here in order from highest to lowest risk): (1) recent CV event (subcategorized by hospitalization for acute coronary syndrome [ACS] or other non-ACS CV event within 90 days of index); (2) coronary heart disease (CHD); (3) history of ischemic stroke; (4) peripheral artery disease (PAD); and (5) diabetes. Outcomes of interest included changes in therapy, proportion of days covered (PDC), time to discontinuation, and proportion of patients with ASCVD-related inpatient visit during the follow-up period. Statin therapy was subdivided into high-intensity treatment (atorvastatin 40 mg or 80 mg, rosuvastatin 20 mg or 40 mg, or simvastatin 80 mg) or moderate- to low-intensity treatment (all other statins and statin dosing regimens). Follow-up data were obtained from the index date (statin initiation) until the end of continuous enrollment. RESULTS: A total of 541,221 patients were included in the analysis. The majority of patients were stratified in the diabetes cohort (61.1%), followed in frequency by recent ACS event (15.8%), recent non-ACS CV event (9.9%), PAD (4.7%), CHD (4.4%), and history of ischemic stroke (4.1%). Only 15.0% of the population initiated therapy with a high-intensity statin, and 22.5% of these high-intensity statin initiators switched to a moderate- to low-intensity regimen during the follow-up period. Median time to statin discontinuation was approximately 15 months. Duration of treatment was longer among those who were treated with a high-intensity versus a moderate- to low-intensity statin regimen (21 and 15 months, respectively). The PDC was highest in the recent ACS hospitalization cohort (66.4%) and lowest in the diabetes cohort (55.5%). The PDC was significantly greater among patients who initiated treatment with a high-intensity statin regimen than with a moderate- to low-intensity statin regimen (62.1% vs. 57.5%, respectively; P< 0.001). At 1 year, Kaplan-Meier estimates of the cumulative rates for ASCVD-related hospitalizations ranged from 3.5% (diabetes) to 21.8% (recent ACS hospitalization). CONCLUSIONS: Patients at high risk for CV events are suboptimally dosed with statins, have high rates of discontinuation, and have low rates of adherence. Despite the use of statin therapy, ASCVD-related inpatient visit rates were high, particularly among those patients at highest risk because of a recent ACS hospitalization. Future interventions are required to ensure that high-risk patients are effectively managed to reduce subsequent morbidity and mortality. DISCLOSURES: Support for this research was provided by Regeneron Pharmaceuticals, Tarrytown, New York, and Sanofi US, Bridgewater, New Jersey. Menzin and Lin are employees of Boston Health Economics, which received consulting fees from Sanofi. Friedman is a consultant to Boston Health Economics. Lin, Friedman, and Menzin have received research support from Sanofi US. Sung, Mallya, Panaccio, and Koren are employees of Sanofi US and also have ownership interest in Sanofi US. Sanchez is an employee of and has ownership interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for Merck & Co, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

The economic burden of psoriasis: a systematic literature review.

Costs associated with psoriasis present a considerable economic burden. A previously published review was lacking comprehensive data on biologics. Therefore, a systematic literature review was performed to gain a comprehensive understanding of the economic burden of psoriasis throughout the world. Studies published in the English language between January 2001 and May 2013 reporting the direct and indirect economic burden of psoriasis were identified from PubMed and conference proceedings. Thirty-five studies from 11 countries met the inclusion criteria. In 2004, the annual total cost (direct and indirect) in the USA alone was approximately US$1.40 billion. Among the European countries, the most recent studies reported an annual total cost per patient of €11,928 in Sweden, €8372 in Italy, €2866-6707 in Germany and CDN$7999 in Canada, based on treatment type. Costs associated with psoriasis are high in many countries, indicating a continued need for treatments that offer good value for money.

Treatment sequencing after failure of the first biologic in cost-effectiveness models of psoriasis: a systematic review of published models and clinical practice guidelines.

OBJECTIVES: To analyse the treatment sequencing assumptions after failure on a first-line biologic in cost-effectiveness models of treatment of moderate to severe plaque psoriasis, and to compare them with the most recent treatment guidelines. METHODS: A systematic search of MEDLINE, Embase, EconLit and the Cochrane Library databases used free text and Medical Subject Headings terms including psoriasis, biologic therapies indicated for psoriasis, and all types of economic evaluations. Two researchers performed 2-level abstract screening for articles meeting pre-specified inclusion criteria. Assumptions about treatment pathways after first-line biologic failure in the cost-effectiveness models were analysed. A second systematic search was performed for psoriasis clinical practice guidelines. Sequence assumptions were compared with treatment guideline recommendations. RESULTS: Of 25 cost-effectiveness modelling studies identified, ten estimated the incremental cost per responder; time horizons varied (12 weeks-18 months) and treatment sequencing was not considered. In 15 studies where treatment sequencing was considered, with time horizons up to 10 years, five studies included only a switch to nonsystemic therapy or best supportive care after first-line biologic failure. Another five of the 15 treatment-pathway studies were available only as abstracts with no details of the sequence assumptions. In five of the 15 studies, first-line biologic failure was followed by second-line biologic monotherapy, one of the recommendations in current treatment guidelines. In only one of these five studies was the efficacy of the second-line biologic adjusted downwards, compared with first-line treatment. Only one of these studies considered dose titration with a first-line biologic and none combination therapy (biologic plus methotrexate or phototherapy) after first-line biologic failure, as recommended in some treatment guidelines. CONCLUSIONS: Cost-effectiveness models of first-line biologics for moderate to severe plaque psoriasis either do not include subsequent treatment regimens or include only some of the regimens recommended in current treatment guidelines. Results may be sensitive to assumptions about treatment sequencing and the choice and efficacy of subsequent treatment regimens.

Healthcare costs and utilization for privately insured patients treated for non-infectious uveitis in the USA.

BACKGROUND: The purpose of this study was to describe comorbidities, healthcare costs, and resource utilization among patients with chronic non-infectious uveitis initiating corticosteroid, immunosuppressants, or biologics.In this retrospective cohort study, patients with a non-infectious uveitis diagnosis and continuous insurance coverage during a 6-month baseline were selected from a privately insured claims database with 80.7 million enrollees. Index dates were defined as the first prescription/administration of a corticosteroid, immunosuppressant, or biologic between 2003 and 2009. Comorbidities, healthcare costs, and utilization were analyzed in a per-member-per-month (PMPM) framework to account for varying between-patient treatment periods, defined as continuous medication use within the same class. Wilcoxon rank-sum and chi-square tests were used for comparisons of costs and categorical outcomes. RESULTS: Patients on corticosteroids (N = 4,568), immunosuppressants (N = 5,466), and biologics (N = 1,694) formed the study population. Baseline PMPM inpatient admission rates were 0.029 for patients on corticosteroids, 0.044 for patients on immunosuppressants, and 0.045 for patients on biologics (p < 0.001 immunosuppressants or biologics versus corticosteroids); during treatment, PMPM inpatient admissions increased to 0.044 and 0.048 for patients taking corticosteroids and immunosuppressants, respectively, but decreased to 0.024 for patients taking biologics (p < 0.001 versus corticosteroids and p = 0.003 versus immunosuppressants). Baseline average PMPM costs for patients taking corticosteroids, immunosuppressants, and biologics were US$935, US$1,738, and US$1,439 (p < 0.001 between groups), while on-treatment PMPM costs excluding drug costs increased to US$1,129 for patients taking corticosteroids but lowered to US$1,592 for patients taking immunosuppressants, and US$918 for patients taking biologics (p < 0.001 versus corticosteroids or immunosuppressants). CONCLUSIONS: There is significant economic burden associated with existing treatments of uveitis. Corticosteroids may be overused as a treatment for uveitis.