Cost Effectiveness of Gemtuzumab Ozogamicin in the First-Line Treatment of Acute Myeloid Leukaemia in the UK.

BACKGROUND AND OBJECTIVE: The phase III ALFA-0701 study demonstrated the efficacy and safety of gemtuzumab ozogamicin (GO) versus standard of care (SOC) chemotherapy (daunorubicin and cytarabine) for the treatment of adult patients with de novo CD33+ acute myeloid leukaemia (AML). This study analysed the cost-effectiveness of GO from the perspective of the UK health care payer. METHODS: A cohort state-transition model was developed to estimate direct health care costs and quality-adjusted life-years (QALYs) over a lifetime time horizon from AML diagnosis to death using monthly cycles. Data on complete remission, overall survival, relapse-free survival (RFS), haematopoietic stem-cell transplantation, and adverse events for GO plus SOC versus SOC were obtained from the ALFA-0701 study. Overall survival and RFS were extrapolated beyond the trial horizon using mixture cure models. Unit costs were obtained from standard national sources. Utilities were identified in a systematic literature review. Costs and outcomes were discounted at 3.5%. Analyses were performed for the base-case population, excluding patients with an unfavourable cytogenetic profile, and the overall population. RESULTS: For the base-case and overall populations respectively, incremental per-patient costs (£13,456 and £14,773) and QALYs (0.99 and 0.68) for GO plus SOC versus SOC resulted in incremental cost-effectiveness ratios (ICERs) of £13,561 and £21,819 per QALY gained. The mean probabilistic ICERs were £14,217 and £23,245, respectively. Univariate sensitivity analyses supported the robustness of the results. CONCLUSIONS: The ICERs for both populations met NICE's £20,000-£30,000 willingness-to-pay threshold for medicines and supported the current approval for GO.

Cost-Effectiveness Analysis of Gemtuzumab Ozogamicin for First-Line Treatment of Patients with Cd-33 Positive Acute Myeloid Leukaemia in Spain.

OBJECTIVE: To assess the incremental cost-utility ratio (ICUR) of gemtuzumab ozogamicin (GO) + standard of care (SOC) vs SOC alone for treatment of patients with de novo AML from a Spanish Health Service perspective. METHODS: A cohort state-transition model, with 12 health-states, was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-years (QALYs) in AML patients with favourable, intermediate, and unknown cytogenetic profiles. Patient profile was defined based on the ALFA-0701 trial. Therapeutic regimens were defined by 5 haematologists. SOC was assumed to be idarubicin and cytarabine, the combination most used in Spain. QALYs were estimated by applying utilities for the time spent by the cohort in each health-state and utility decrements associated with adverse events (AE). Total cost (€,2020) included drug-acquisition, hematologic stem-cell transplantation, disease management, AE management and end-of-life costs. Unit costs were derived from local databases. All parameters were validated by haematologist. Costs and outcomes were discounted (3%/year). RESULTS: Higher cost/patient (€177,618 vs €151,434) and greater QALYs (5,70 vs 4,62) were obtained with GO+SOC vs SOC. The ICUR was €24,203/QALY gained. CONCLUSION: This simulation suggests that GO + SOC could be a cost-effective option for treatment of patients with de novo AML in first line.

Health state utility values in major depressive disorder treated with pharmacological interventions: a systematic literature review.

BACKGROUND: Major depressive disorder (MDD) is associated with decreased patient well-being and symptoms that can cause substantial impairments in patient functioning and even lead to suicide. Worldwide, MDD currently causes the second-most years lived with disability and is predicted to become the leading cause of disability by 2030. Utility values, capturing patient quality of life, are required in economic evaluations for new treatments undergoing reimbursement submissions. We aimed to identify health state utility values (HSUVs) and disutilities in MDD for use in future economic evaluations of pharmacological treatments. METHODS: Embase, PubMed, Econlit, and Cochrane databases, plus gray literature, were searched from January 1998 to December 21, 2018, with no language or geographical restrictions, for relevant studies that reported HSUVs and disutilities for patients with MDD receiving pharmacological interventions. RESULTS: 443 studies were identified; 79 met the inclusion criteria. We focused on a subgroup of 28 articles that reported primary utility data from 16 unique studies of MDD treated with pharmacological interventions. HSUVs were elicited using EQ-5D (13/16, 81%; EQ-5D-3L: 11/16, 69%; EQ-5D-3L or EQ-5D-5L not specified: 2/16), EQ-VAS (5/16, 31%), and standard gamble (1/16, 6%). Most studies reported baseline HSUVs defined by study entry criteria. HSUVs for a first or recurrent major depressive episode (MDE) ranged from 0.33 to 0.544 and expanded from 0.2 to 0.61 for patients with and without painful physical symptoms, respectively. HSUVs for an MDE with inadequate treatment response ranged from 0.337 to 0.449. Three studies reported HSUVs defined by MADRS or HAMD-17 clinical thresholds. There was a large amount of heterogeneity in patient characteristics between the studies. One study reported disutility estimates associated with treatment side effects. CONCLUSIONS: Published HSUVs in MDD, elicited using methods accepted by health technology assessment bodies, are available for future economic evaluations. However, the evidence base is limited, and it is important to select appropriate HSUVs for the intervention being evaluated and that align with clinical health state definitions used within an economic model. Future studies are recommended to elicit HSUVs for new treatments and their side effects and add to the existing evidence where data are lacking.

Budget Impact Analysis of Gemtuzumab Ozogamicin for the Treatment of CD33-Positive Acute Myeloid Leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML. OBJECTIVE: The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period. METHODS: We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis. RESULTS: Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting. CONCLUSIONS: The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML.

Economic Evaluations of New Oral Anticoagulants for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement: A Systematic Review.

BACKGROUND: Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a venous thromboembolism (VTE). New oral anticoagulants (NOACs) may be more effective at preventing VTEs but are associated with more bleeding events versus traditional anticoagulants. OBJECTIVE: The objective of this systematic review was to identify published economic analyses of NOACs for primary VTE prophylaxis following THR and TKR surgeries, and to summarise the modelling techniques used and the cost-effectiveness results. METHODS: Electronic searches of MEDLINE, EconLit and The Cochrane Library were performed from January 2008 to February 2015. Reference lists of included articles and reviews were examined for relevant studies. RESULTS: Sixteen relevant economic analyses were identified, all of which used decision-tree structures to model acute events after surgery; 13 included a chronic-phase Markov module to capture long-term complications of VTE and recurrent VTE events. All studies included prophylaxis-related major bleeding events and captured both symptomatic and asymptomatic VTE-related events; nine studies distinguished between distal and proximal deep vein thrombosis events. Overall, rivaroxaban dominated enoxaparin in eight of 11 studies and dalteparin in one study, dabigatran dominated enoxaparin in five of seven studies and apixaban dominated enoxaparin in two of two studies. Rivaroxaban dominated dabigatran in four of four studies, apixaban dominated dabigatran in two of two studies and rivaroxaban dominated apixaban in one study. CONCLUSIONS: The economic analyses showed reasonable consistency in the model structures used and the events captured. The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin. Dabigatran appeared to be the least cost effective NOAC. More research is needed to assess the cost effectiveness of apixaban and edoxaban.