Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia.

OBJECTIVES: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs). METHODS: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective. This model included states for progression-free survival (PFS), post-progression survival (PPS) and death. PFS and overall survival (OS) were parametrically extrapolated from ibrutinib publications and a preliminary hazard ratio based on phase I/II data was applied for acalabrutinib. Deterministic and probabilistic sensitivity analyses were performed, and 1296 scenarios were assessed. RESULTS: The base-case incremental cost-effectiveness ratio (ICER) was £61,941/QALY, with 3.44 incremental QALYs and incremental costs of £213,339. Deterministic sensitivity analysis indicated that survival estimates, utilities and treatment costs of ibrutinib and acalabrutinib and resource use during PFS have the greatest influence on the ICER. Probabilistic results under different development scenarios indicated that greater efficacy of acalabrutinib would decrease the likelihood of cost effectiveness (from 63% at no effect to 2% at maximum efficacy). Scenario analyses showed that a reduction in PFS did not lead to great QALY differences (- 8 to - 14% incremental QALYs) although it did greatly affect costs (- 47 to - 122% incremental pounds). For OS, the opposite was true (- 89 to - 93% QALYs and - 7 to - 39% pounds). CONCLUSIONS: Acalabrutinib is not likely to be cost effective compared with ibrutinib under current development scenarios. The conflicting effects of OS, PFS, drug costs and utility during PFS show that determining the cost effectiveness of acalabrutinib without insight into all parameters complicates health technology assessment decision making. Early assessment of the cost effectiveness of new products can support development choices and reimbursement processes through effective early dialogues between stakeholders.

The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use.

On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM+LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM+LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rank p value <.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).

Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital.

INTRODUCTION: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. METHODS: Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. RESULTS: Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. CONCLUSION: Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.

Cost-effectiveness analysis of liraglutide versus sitagliptin or exenatide in patients with inadequately controlled Type 2 diabetes on oral antidiabetic drugs in Greece.

BACKGROUND: To evaluate the long-term cost-effectiveness of liraglutide versus sitagliptin or exenatide, added to oral antidiabetic drug mono- or combination therapy respectively, in patients with Type 2 diabetes in Greece. METHODS: The CORE Diabetes Model, a validated computer simulation model, was adapted to the Greek healthcare setting. Patient and intervention effects data were gathered from a clinical trial comparing liraglutide 1.2 mg once daily vs. sitagliptin 100 mg once daily, both combined with metformin, and a clinical trial comparing liraglutide 1.8 mg once daily vs. exenatide 10 µg twice daily, both as add-on to metformin, glimepiride or both. Direct costs were reported in 2013 Euros and calculated based on published and local sources. All future outcomes were discounted at 3.5% per annum, and the analysis was conducted from the perspective of a third-party payer in Greece. RESULTS: Over a patient's lifetime, treatment with liraglutide 1.2 mg vs. sitagliptin drove a mean increase in discounted life expectancy of 0.13 (SD 0.23) years and in discounted quality-adjusted life expectancy of 0.19 (0.16) quality-adjusted life years (QALYs), whereas therapy with liraglutide 1.8 mg vs. exenatide yielded increases of 0.14 (0.23) years and 0.19 (0.16) QALYs respectively. As regards lifetime direct costs, liraglutide 1.2 mg resulted in greater costs of €2797 (€1468) versus sitagliptin, and so did liraglutide 1.8 mg compared with exenatide (€1302 [€1492]). Liraglutide 1.2 and 1.8 mg doses were associated with incremental cost effectiveness ratios of €15101 and €6818 per QALY gained, respectively. CONCLUSIONS: Liraglutide is likely to be a cost-effective option for the treatment of Type 2 diabetes in a Greek setting.

Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of treatment response in myeloma. MATERIALS AND METHODS: This prospective single-institution study was HIPAA-compliant with local research ethics committee approval. Written informed consent was obtained from each subject. Eight healthy volunteers (cohort 1a) and seven myeloma patients (cohort 1b) were imaged twice to assess repeatability of quantitative apparent diffusion coefficient (ADC) estimates. Thirty-four additional myeloma patients (cohort 2) underwent whole-body DW imaging before treatment; 26 completed a posttreatment imaging. Whole-body DW data were compared before and after treatment by using qualitative (ie, observer scores) and quantitative (ie, whole-body segmentation of marrow ADC) methods. Serum paraproteins and/or light chains or bone marrow biopsy defined response. RESULTS: Whole-body DW imaging scores were significantly different between observers (P < .001), but change in scores between observers after treatment was not (P = .49). Sensitivity and specificity for detecting response according to observer scores were 86% (18 of 21 patients) and 80% (4 of 5 patients) for both observers. ADC measurement was repeatable: mean coefficient of variation was 3.8% in healthy volunteers and 2.8% in myeloma patients. Pretreatment ADC in cohort 2 was significantly different from that in cohort 1a (P = .03), but not from that in cohort 1b (P = .2). Mean ADC increased in 95% (19 of 20) of responding patients and decreased in all (five of five) nonresponders (P = .002). A 3.3% increase in ADC helped identify response with 90% sensitivity and 100% specificity; an 8% increase (greater than repeatability of cohort 1b) resulted in 70% sensitivity and 100% specificity. There was a significant negative correlation between change in ADC and change in laboratory markers of response (r = -0.614; P = .001). CONCLUSION: Preliminary work demonstrates whole-body DW imaging is a repeatable, quantifiable technique for assessment of treatment response in myeloma.

Comparative cost-effectiveness models for the treatment of multiple myeloma.

OBJECTIVES: To compare cost effectiveness models for the first-line treatment of multiple myeloma, and explore the differences between the models' structure, parameters, assumptions and results. METHODS: Three cost effectiveness models for the treatment of multiple myeloma, were compared that had been developed to inform resource allocation in the UK for the chemotherapy regimens bortezomib, melphalan and prednisolone (BMP); and melphalan, prednisolone and thalidomide (MPT) versus melphalan and prednisolone (MP). The models used alternative approaches and assumptions to estimate the overall survival and progression-free survival for each of the interventions. Through the use of sensitivity analyses, the most influential parameters and assumptions of each of the models were identified. RESULTS: The models developed by the manufacturers gave conflicting results, with each manufacturer favouring their drug. The differences between the model results were determined by two parameters: the hazard ratio for overall survival for MPT vs. MP and the cost of bortezomib. CONCLUSIONS: Using models developed for assessing treatments for multiple myeloma we demonstrated that it was feasible to compare models, which then aided decision makers in making reimbursement decisions.

Assessment of AACE/ACE recommendations for initial dual antihyperglycemic therapy using the fixed-dose combination of sitagliptin and metformin versus metformin.

OBJECTIVE: The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) diabetes algorithm recommends a stratified approach to initial therapy to achieve a glycated hemoglobin (HbA1c) goal of ≤6.5% in patients with type 2 diabetes mellitus (T2DM) who have inadequate glycemic control. Data from a double-blind study in drug-naïve T2DM patients comparing initial monotherapy with metformin (MET) with initial dual therapy with a fixed-dose combination of sitagliptin and MET (SITA/MET FDC) was used to determine AACE/ACE HbA1c goal attainment in these treatment groups. METHODS: A total of 1,250 patients (mean baseline HbA1c = 9.9%) were randomized 1:1 to SITA/MET FDC 50/500 mg twice daily (b.i.d.) or MET 500 mg b.i.d. for 18 weeks. SITA/MET FDC and MET were uptitrated over 4 weeks to 50/1,000 mg b.i.d. and 1,000 mg b.i.d., respectively. RESULTS: At week 18, a higher percentage of patients receiving SITA/MET FDC had HbA1c levels ≤6.5% and <7% than those receiving MET alone within each of the 3 AACE/ACE HbA1c categories (6.5-7.5%, >7.5-9.0%, and >9.0%). Of patients with a baseline HbA1c >7.5-9.0% who initiated SITA/MET FDC, 48.6% achieved an HbA1c ≤6.5% at week 18 compared with 23.1% of patients who initiated MET monotherapy (P<.001). In patients with a baseline HbA1c >9.0%, 24.0% on SITA/MET FDC achieved an HbA1c ≤6.5% compared with 12.8% on MET alone (P<.001). CONCLUSION: In T2DM patients with a baseline HbA1c >7.5-9.0%, substantially more achieved the HbA1c goal of ≤6.5% with initial dual therapy (SITA/MET FDC) than with initial monotherapy (MET), which is in agreement with the AACE/ACE diabetes algorithm.

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy-era with plerixafor and G-CSF has superior efficacy but significantly higher costs compared to mobilization with low-dose cyclophosphamide and G-CSF.

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.

Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE).

OBJECTIVE: The epidemic of type 2 diabetes (T2DM) threatens to become the major public health problem of this century. However, a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted. GRADE, a pragmatic, unmasked clinical trial, aims to compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes. RESEARCH DESIGN AND METHODS: GRADE was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The consensus protocol was approved by NIDDK and the GRADE Research Group. Eligibility criteria for the 5,000 metformin-treated subjects include <5 years' diabetes duration, ≥ 30 years of age at time of diagnosis, and baseline hemoglobin A1c (A1C) of 6.8-8.5% (51-69 mmol/mol). Medications representing four classes (sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and insulin) will be randomly assigned and added to metformin (minimum-maximum 1,000-2,000 mg/day). The primary metabolic outcome is the time to primary failure defined as an A1C ≥ 7% (53 mmol/mol), subsequently confirmed, over an anticipated mean observation period of 4.8 years (range 4-7 years). Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C >7.5% (58 mmol/mol) and, ultimately, the need to implement an intensive basal/bolus insulin regimen. The four drugs will also be compared with respect to selected microvascular complications, cardiovascular disease risk factors, adverse effects, tolerability, quality of life, and cost-effectiveness. CONCLUSIONS: GRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM. GRADE begins recruitment at 37 centers in the U.S. in 2013.

Health care costs and resource utilization, including patient burden, associated with novel-agent-based treatment versus other therapies for multiple myeloma: findings using real-world claims data.

BACKGROUND: . Treatment of multiple myeloma has dramatically improved with the introduction of bortezomib (BOR), thalidomide (THAL), and lenalidomide (LEN). Studies assessing health care costs, particularly economic burden on patients, are limited. We conducted a claims-based, retrospective analysis of total health care costs as well as patient burden (patient out-of-pocket costs and number of ambulatory/hospital visits) associated with BOR/THAL/LEN treatment versus other therapies (OTHER). METHODS. Treatment episodes starting between January 1, 2005 and September 30, 2010 were identified from the claims database of a large U.S. health plan. Health care costs and utilization were measured during 1 year after initiation and analyzed per treatment episode. Multivariate analyses were used to adjust for patient characteristics, comorbidities, and line of treatment. RESULTS: A total of 4,836 treatment episodes were identified. Mean adjusted total costs were similar between BOR ($112,889) and OTHER ($111,820), but higher with THAL ($129,412) and LEN ($158,428). Mean adjusted patient out-of-pocket costs were also similar for BOR ($3,846) and OTHER ($3,900) but remained higher with THAL ($4,666) and LEN ($4,483). Mean adjusted rates of ambulatory visits were similar across therapies (BOR: 69.67; THAL: 66.31; LEN: 65.60; OTHER: 69.42). CONCLUSIONS: Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data.

The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Real-world health care costs of relapsed/refractory multiple myeloma during the era of novel cancer agents.

WHAT IS KNOWN AND OBJECTIVE: High costs of novel agents increasingly put pressure on limited healthcare budgets. Demonstration of their real-world costs and cost-effectiveness is often required for reimbursement. However, few published economic evaluations of novel agents for multiple myeloma exist. Moreover, existing cost analyses were heavily based on conventionally treated patients. We investigated real-world health care costs of relapsed/refractory multiple myeloma in Dutch daily practice. METHODS: A retrospective medical chart review was conducted for 139 patients treated between January 2001 and May 2009. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-, thalidomide- and lenalidomide-based treatment regimens. RESULTS: Mean monthly total costs (€3,981) varied depending on the sequence of therapy (range: €442-€31,318). Significant cost drivers across all regimens included costs of therapy and hospital admissions. The acquisition costs for novel agents in particular accounted for 32% of mean total monthly costs. Prognostic factors associated with increased mean total monthly costs in multivariate regression analysis included low platelet counts (P = 0·01) and worsening performance status (P < 0·001). Mean total monthly costs of bortezomib- and lenalidomide-based regimens were significantly higher than those for thalidomide-based regimens in second, third and fourth treatment line. WHAT IS NEW AND CONCLUSIONS: Real-world costs during treatment of relapsed/refractory multiple myeloma vary greatly. Cost drivers include hospital admissions and acquisition costs of novel agents. Costs also vary by prognostic factors and treatment-related resource use. Future studies assessing the costs of combination therapy consisting of two or more novel agents are encouraged.

Long-term clinical and economic outcomes associated with liraglutide versus sitagliptin therapy when added to metformin in the treatment of type 2 diabetes: a CORE Diabetes Model analysis.

BACKGROUND: A recent open-label, parallel group trial showed that liraglutide is superior to sitagliptin for reduction of HbA1c, and is well tolerated with minimum risk of hypoglycemia. Although these findings support the use of liraglutide as an effective GLP-1 agent to add to metformin, the value of liraglutide needs to be quantified in the framework of a cost-effectiveness (CE) analysis in a US setting. OBJECTIVE: This current study sets out to assess the long-term cost-effectiveness outcomes of liraglutide vs sitagliptin based on treatment effects data from the 1860-LIRA-DPP-4 52-week trial. METHODS: The IMS CORE Diabetes Model (CDM), a non-product-specific, validated computer simulation model that projects the long-term outcomes related to interventions for type 2 diabetes, is used for simulation of these interventions. In the model, patients were treated initially on one of the three treatment options: liraglutide 1.2 mg daily, 1.8 mg daily, or sitagliptin 100 mg daily, each used as add-on therapy to metformin for 5 years. After 5 years all patients switched to basal insulin treatment for the remainder of the simulation (35-year time horizon overall). Incremental cost-effectiveness ratios (ICERs) were generated for liraglutide 1.2 mg compared with sitagliptin and liraglutide 1.8 mg compared with sitagliptin. Transition probabilities, health state utility values, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the US. Sensitivity analyses were performed to test robustness of the base case scenario. RESULTS: For liraglutide 1.8 mg vs sitagliptin, the ICER was $37,234 per QALY gained, while for liraglutide 1.2 mg vs sitagliptin, the ICER was $25,742 per QALY gained. In all sensitivity analyses, including setting the change in HbA1c to the lower limits of the 95% confidence intervals, the ICERs remained below US$ 50,000/QALY, a commonly accepted threshold in the US, except for the shortest time horizon of 10 years. CONCLUSIONS: The availability of liraglutide 1.2 mg and 1.8 mg with improved efficacy profiles over sitagliptin could improve patient care, with the incremental cost effectiveness ratio below $50,000 per QALY gained as add-on to metformin.

Long-term cost-consequence analysis of exenatide once weekly vs sitagliptin or pioglitazone for the treatment of type 2 diabetes patients in the United States.

OBJECTIVE: Exenatide once-weekly (ExQW) is a GLP-1 receptor agonist shown to lower glucose and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the clinical benefits and associated economic benefits of treatment with ExQW compared with sitagliptin or pioglitazone in the US. METHODS: The IMS CORE Diabetes Model, a validated computer simulation model, was used to project lifetime clinical outcomes and complication costs. The costs of glucose-lowering drugs were excluded as not all prices were available. Baseline patient characteristics (mean values: age, 52.5 years; diabetes duration, 6 years; HbA1(c), 8.51%; body mass index, 32.12 kg/m(2)) and clinical data were derived from a phase 3 clinical trial that compared ExQW with sitagliptin or pioglitazone in T2DM patients. At 6 months, patients treated with ExQW had greater improvements in HbA1(c) and body weight than those treated with sitagliptin or pioglitazone. Complication costs were extracted from published sources. Health outcomes and costs were discounted at 3% per year. Sensitivity analyses were performed. RESULTS: Over 35 years, and compared with sitagliptin or pioglitazone, ExQW increased life expectancy by, respectively, 0.28 (13.76 ± 0.17 vs 13.48 ± 0.18) and 0.17 years (13.76 ± 0.17 vs 13.59 ± 0.17), and quality-adjusted life years by, respectively, 0.28 (9.56 ± 0.12 vs 9.28 ± 0.12) and 0.24 years (9.56 ± 0.12 vs 9.32 ± 0.12). ExQW was associated with lower lifetime complication costs: compared with sitagliptin or pioglitazone, ExQW saved, respectively US$2215 (US$55,647 ± 2039 vs US$57,862 ± 2159) and US$933 (US$55,647 ± 2039 vs US$56,580 ± 2007) direct cost per patient. Cost-savings resulted mainly from a lower projected cumulative incidence of cardiovascular diseases and neuropathic complications. LIMITATIONS: Short-term changes in surrogate end-points were used to project lifetime effects on clinical outcomes. Pharmacy costs were excluded from the analyses. CONCLUSIONS: Over a patient's lifetime, ExQW was projected to improve health and decrease diabetes-related complication costs compared with sitagliptin or pioglitazone.

Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus.

AIM: To investigate the cost-effectiveness of liraglutide as add-on to metformin vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with first-line metformin. METHODS: Data were sourced from a clinical trial comparing liraglutide vs. glimepiride, both in combination with metformin, and a clinical trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only the subgroup of patients in whom liraglutide was added to metformin monotherapy was included in the cost-utility analysis. The CORE Diabetes Model was used to simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly from the trials. Costs and outcomes were discounted at 3.5% per annum and costs were accounted from a third-party payer (UK National Health System) perspective. RESULTS: Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in mean increases in quality-adjusted life expectancy of 0.32 ± 0.15 and 0.28 ± 0.14 quality-adjusted life years vs. glimepiride, and 0.19 ± 0.15 and 0.31 ± 0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher costs of £ 3003 ± £ 678 and £ 4688 ± £ 639 vs. glimepiride, and £ 1842 ± £ 751 and £ 3224 ± £ 683 vs. sitagliptin, over a patient's lifetime. Both liraglutide doses were cost-effective, with incremental cost-effectiveness ratios of £ 9449 and £ 16,501 per quality-adjusted life year gained vs. glimepiride, and £ 9851 and £ 10,465 per quality-adjusted life year gained vs. sitagliptin, respectively. CONCLUSIONS: Liraglutide, added to metformin monotherapy, is a cost-effective option for the treatment of Type 2 diabetes in a UK setting.

Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents.

The ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo-secretory or non-secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, lenalidomide and/or bortezomib. We show that although M protein appears to outperform sFLC comparatively over the course of induction therapy, the addition of FLC to M protein further informs the characterization of residual disease status post-induction. Moreover, sFLC at the time of stem cell mobilization appears to hold prognostic power for survival endpoints following high-dose chemotherapy/autologous stem cell transplant (HDC/SCT). These findings suggest potentially novel roles for sFLC in patients with MM with an intact M protein receiving novel agent-based induction strategies followed by HDC/SCT.