A Comparison of Costs among Patients with Type 2 Diabetes Mellitus Who Initiated Therapy with Exenatide or Insulin Glargine

Background: Exenatide (Byetta) and insulin glargine (Lantus) are antidiabetic agents that are typically used after lack of response to an oral antidiabetic agent(s). Although previous research has examined the impact of these medications on glycaemic control, there is little information about the relative costs associated with the medications. Objective: To compare costs among patients with type 2 diabetes mellitus treated with exenatide or insulin glargine from a US third-party payer perspective. Methods: Data from a large, national administrative claims database were used in this study. The intent-to-treat (ITT) cohort included adults who were diagnosed with type 2 diabetes and initiated therapy with either exenatide (n - 4090) or insulin glargine (n - 1660). In addition, included patients were required to have no diagnoses of type 1 diabetes, to have received at least two prescriptions for an oral antidiabetic agent in the 6 months prior to first use of either exenatide or insulin glargine and to have continuous insurance coverage from 6 months before, to 12 months after, initiation on ITT medication. Annual total medical costs and total diabetes-related medical costs, in &dollar;US, year 2007 values, were estimated using stepwise multivariate regressions. Major cost components were also examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, co-morbidities and complications, and timing of treatment initiation. Results: Compared with insulin glargine, initiation of exenatide was associated with significantly lower total direct medical costs (&dollar;US19 293 vs &dollar;US23 782; p < 0.0001), inpatient costs (&dollar;US4121 vs &dollar;US7532; p < 0.0001), outpatient costs (&dollar;US9501 vs &dollar;US12 885; p < 0.0001), emergency department (ED) costs (&dollar;US82 vs &dollar;US131; p < 0.0001), total diabetes-related medical costs (&dollar;US7833 vs &dollar;US8536; p < 0.0001), diabetes-related inpatient costs (&dollar;US2172 vs &dollar;US3538; p < 0.0001) and diabetes-related outpatient costs (&dollar;US2739 vs &dollar;US3249; p < 0.0001). Initiation of exenatide was associated with significantly higher total overall drug costs (&dollar;US6885 vs &dollar;US5936; p < 0.0001) and diabetes-related drug costs (&dollar;US3160 vs &dollar;US2422; p < 0.0001). Conclusions: Compared with the use of insulin glargine, use of exenatide was associated with significantly lower annual total direct medical costs and significantly lower total diabetes-related medical costs, despite higher total drug costs and higher diabetes-related drug costs. In addition, exenatide was associated with significantly lower total inpatient, outpatient, ED, and diabetes-related inpatient and outpatient costs.

Indirect treatment comparisons including network meta-analysis: Lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma.

BACKGROUND:In the absence of clinical trials providing direct efficacy results, this study compares different methods of indirect treatment comparison (ITC), and their respective impacts on efficacy estimates for lenvatinib (LEN) plus everolimus (EVE) combination therapy compared to other second-line treatments for advanced/metastatic renal cell carcinoma (a/mRCC). METHODS:Using EVE alone as the common comparator, the Bucher method for ITC compared LEN + EVE with cabozantinib (CAB), nivolumab (NIV), placebo (PBO) and axitinib (AXI). Hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) estimated the impact of applying three versions of the LEN+EVE trial data in separate ITCs. Last, to overcome exchangeability bias and potential violations to the proportional hazards assumption, a network meta-analysis using fractional polynomials was performed. RESULTS:Bucher ITCs demonstrated LEN + EVE superiority over EVE for PFS, indirect superiority to NIV, AXI, and PBO, and no difference to CAB. For OS, LEN + EVE was superior to EVE and indirectly superior to PBO, applying original HOPE 205 data. Using European Medicines Agency data, LEN + EVE was directly superior to EVE for OS. Fractional polynomial HRs for PFS and OS substantially overlapped with Bucher estimates, demonstrating LEN+EVE superiority over EVE, alone, NIV, and CAB. However, there were no statistically significant results as the credible intervals for HR crossed 1.0. CONCLUSIONS:Comparing three Bucher ITCs, LEN + EVE demonstrated superior PFS when indirectly compared to NIV, AXI, and PBO, and mixed results for OS. While fractional polynomial modelling for PFS and OS failed to find statistically significant differences in LEN + EVE efficacy, the overall HR trends were comparable

Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection

<p><b>Objectives:</b> To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OMB/PTV/r + DSV ± RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection.</p> <p><b>Methods:</b> An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r + DSV ± RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested.</p> <p><b>Results:</b> For genotype 1 treatment-naive HCV patients, for OMB/PTV/r + DSV ± RBV, PegIFN + ribavirin (PegIFN/RBV), sofosbuvir + PegIFN/RBV, telaprevir + PegIFN/RBV, boceprevir + PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r + DSV ± RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses.</p> <p><b>Limitations:</b> A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials.</p> <p><b>Conclusions:</b> OMB/PTV/r + DSV ± RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.</p

Cost-effectiveness of currently recommended direct-acting antiviral treatments in patients infected with genotypes 1 or 4 hepatitis C virus in the US

<p><b>Objective:</b> This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US.</p> <p><b>Methods:</b> A cost-effectiveness analysis of treatments for CHC from a US payer’s perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF + SMV), simeprevir + pegylated interferon/ribavirin (SMV + PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir + ribavirin (2D + R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios.</p> <p><b>Results:</b> In GT1 patients, 3D ± R and SOF-containing regimens have similar long-term outcomes; 3D ± R had the lowest lifetime risks of all liver disease outcomes: CC = 30.2%, DCC = 5.0 %, HCC = 6.8%, LT = 1.9% and LrD = 9.2%. In GT1 patients, 3D ± R had the lowest cost and the highest QALYs. As a result, 3D ± R dominated these treatment options. In GT4 patients, 2D + R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT.</p> <p><b>Limitations:</b> While the results are based on input values, which were obtained from a variety of heterogeneous sources—including clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses.</p> <p><b>Conclusions:</b> Among currently recommended treatments for GT1 and GT4 in the US, 3D ± R (for GT1) and 2D + R (for GT4) have a favorable cost-effectiveness profile.</p