Treatment intensification with bempedoic acid to achieve LDL-C goal in patients with ASCVD: A simulation model using a real-world patient cohort in the US.

Background and aims: Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended. Methods: The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality. Results: Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively. Conclusions: This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

Lipid-lowering therapy and LDL-C control for primary prevention in persons with diabetes across 90 health systems in the United States.

Objective: National guidelines recommend statin therapy for patients with type 2 diabetes. We assessed the extent of moderate- to high-intensity statin therapy utilization in community practice. Methods: We evaluated lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) levels at baseline and 1-year follow-up in patients aged 40-75 years with type 2 diabetes but without atherosclerotic cardiovascular disease (ASCVD), across 90 health systems in the United States participating in an electronic health record-derived dataset, Cerner Real-World Data. Multivariable logistic regression was used to evaluate factors associated with utilization of moderate- to high-intensity statin. Results: We identified 241,232 patients with type 2 diabetes (58.1 % on moderate- to high-intensity statin, 7.0 % on low-intensity statin, and 34.9 % on no statin). Predictors of moderate- to high-intensity statin therapy included retinopathy (adjusted odds ratio [aOR], 1.26; 95 % confidence interval [CI], 1.15-1.38), hypertension (aOR, 1.52; 95 % CI, 1.43-1.61), and stage 3 chronic kidney disease (aOR, 1.14; 95 % CI, 1.07-1.21). Women (aOR, 0.85; 95 % CI, 0.82-0.87), and those with rheumatoid arthritis (aOR, 0.79; 95 % CI, 0.71-0.87), psoriasis (aOR, 0.85; 95 % CI, 0.75-0.96), and hepatitis C (aOR, 0.40; 95 % CI, 0.39-0.46), had reduced odds of moderate- to high-intensity statin treatment. Utilization of ezetimibe was rare (2.0 %). LDL-C control was suboptimal at baseline (37.0 % and 27.9 % had LDL-C ≥100 mg/dL and <70 mg/dL, respectively). At 1-year follow-up, the rate of moderate- to high-intensity statin therapy utilization was 65.3 %. Conclusion: Increased efforts are needed to improve LDL-C control and LLT use for primary prevention of ASCVD in adults with type 2 diabetes, in particular among women and those with risk-enhancing inflammatory conditions.

Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies.

OBJECTIVE: The results from basket trials utilized to gain regulatory approval of tumor-agnostic therapies can be difficult to interpret without the context of a comparator arm. We describe the role and efficacy of histology-based treatments to provide a historical comparison with larotrectinib. METHODS: A systematic literature review (SLR) was conducted on the clinical outcomes of current histology-based standard of care treatments used in non-small cell lung cancer, colorectal cancer, thyroid cancer, gliomas, soft tissue sarcoma, salivary gland cancer, and infantile fibrosarcoma (7 of the 21 tumor histologies in the larotrectinib trials). The review focused on advanced stage/metastatic disease to make a historical comparison with larotrectinib. RESULTS: Larotrectinib provides positive outcomes in both adult and pediatric patients with advanced or metastatic solid tumors known to harbor NTRK gene fusions across a wide range of tumor types. Although the numbers of patients per tumor type are limited, the results of this historical comparison demonstrated that larotrectinib is an efficacious treatment option when naïvely indirectly compared with historical treatments across all 7 reviewed tumor types, especially in comparison to later lines of therapy. CONCLUSIONS: Utilizing larotrectinib as a case example across these types of historical comparisons shows that larotrectinib provides positive efficacy outcomes in TRK fusion cancer across tumor histologies known to harbor NTRK gene fusions that may be preferable to historical treatments.

Costs associated with long-acting insulin analogues in patients with diabetes.

OBJECTIVES: The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents, including human insulin, oral antidiabetic drugs, and other injectable therapies, in the treatment of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). STUDY DESIGN: A systematic review of the medical literature (MEDLINE, EMBASE, Cochrane, EconLit) conducted from 2004 to 2016. METHODS: The review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria for studies were: patients with T1D and/or T2D, LAIA intervention, and comparators, including oral antidiabetics (OADs) or neutral protamine Hagedorn (NPH). Outcomes of interest were adherence measures; economic outcomes, including total costs, cost savings, and willingness-to-pay; and cost-effectiveness or incremental cost-effectiveness analyses. Real-world costs of individual LAIAs were also evaluated and are often compared against those of other LAIAs in the economic analyses. RESULTS: We identified and included 117 relevant studies. Patients using LAIAs had higher drug costs than those using OADs and NPH but had neutral or reduced total and diabetes-related costs compared with patients using non-LAIAs. Use of LAIA pen-delivery systems may lead to improved adherence and reduction in costs. Patients receiving insulin glargine demonstrated higher adherence and persistence than patients on insulin detemir. Economic models suggest that LAIAs are more cost-effective than NPH for T1D; for T2D, insulin glargine is more costly than NPH but less so than insulin detemir. CONCLUSIONS: Despite higher drug costs, the real-world overall medical costs of LAIAs are not significantly different from those of NPH in patients with diabetes. The findings may be helpful for formulary decision making for patients with diabetes in a cost-constrained environment.

Review of outcomes associated with restricted access to atypical antipsychotics.

OBJECTIVES: Cost containment policies, such as prior authorization (PA), have increasingly been used by formulary decision makers to manage drug spending of the atypical antipsychotic (AAP) drug class. However, these drug cost containment policies may result in cost shifting rather than cost savings. Given the interest in coordination of care, the objective of this study was to evaluate the impact of restricted access to AAPs on healthcare costs and health outcomes in individuals with schizophrenia or bipolar disorder. STUDY DESIGN: Narrative literature review. METHODS: A literature search was conducted using MEDLINE (via PubMed) for studies published between January 1993 and December 2013. RESULTS: A total of 15 published studies were identified that evaluated restricted access to AAPs in regard to healthcare costs or health outcomes: 11 studies assessed PAs, 2 studies assessed carve-outs, 1 study assessed a payment limit (cap), and 1 study assessed Medicare Part D cost sharing. Among 8 studies evaluating changes in pharmacy costs and clinical outcomes, 5 studies reported that formulary restrictions were associated with pharmacy cost savings and increases in healthcare utilization or treatment discontinuation. Of the 4 studies that measured overall cost changes, 3 studies reported increases in overall cost burden and 1 study showed modest cost savings associated with formulary restrictions. CONCLUSIONS: Study findings revealed there exists a gap in the literature as to whether restricted access to AAPs results in overall cost savings or, rather, shifts the cost burden from pharmacy spending to other parts of the healthcare system, such as service utilization.

Achieving Balance with the AMCP Format for Formulary Submissions, Version 4.0: A Dossier Producer's Perspective.

DISCLOSURES: Both authors are employed by Xcenda and develop AMCP Format dossiers.

Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review.

OBJECTIVE: The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. METHODS: A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. RESULTS: A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to $26,471.80 for nonfatal myocardial infarction, and per-event costs as high as $18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. CONCLUSION: Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers.

The burden of psoriatic arthritis: a literature review from a global health systems perspective.

OBJECTIVE: We sought to evaluate the clinical, economic, and humanistic burden of illness in patients with psoriatic arthritis (PsA). STUDY DESIGN: We performed a literature review. METHODS: Our literature search, conducted between 1998 and 2009, included published studies that (1) considered the direct and indirect costs of PsA; reported measures of clinical burden, including mortality, physical function, quality of life, and productivity; and (3) reported comorbid conditions in patients with PsA. RESULTS: We retrieved and reviewed a total of 49 studies. Compared with the general population, patients with PsA had lower health-related quality of life and an increased risk of co-morbid conditions, especially cardiovascular disease. In the U.S., the direct annual health care costs for PsA are estimated to be as high as $1.9 billion. Total indirect costs associated with PsA account for 52% to 72% of total costs. Both direct and indirect costs of PsA increase with worsening physical function and disease activity. CONCLUSION: PsA imposes a considerable economic and quality-of-life burden to patients and society. Clinical features of PsA, including comorbid conditions and disease activity, contribute to reduced physical and psychosocial health-related quality of life. The clinical burden of PsA contributes to direct medical costs attributable to the utilization of health care resources. As a result of the physical functioning limitations imposed by PsA, indirect costs such as disability and lost productivity are substantial drivers of the total costs of care.