Cost effectiveness of duloxetine in the treatment of fibromyalgia in the United States

Abstract

Objective:

To evaluate the cost effectiveness of duloxetine when considered as an alternative treatment for patients in the United States (US) being treated for fibromyalgia pain.

Research design and methods:

A Markov model was used to evaluate the economic and clinical advantages of duloxetine in controlling fibromyalgia pain symptoms over a 2-year time horizon. A base-case treatment sequence was adopted from clinical guidelines, based on tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, anticonvulsants, and opioids. Treatment response was modeled using changes from baseline in pain severity, and response thresholds: full response (at least a 50% change), response (30–49% change), and no response (less than a 30% change). Clinical efficacy and discontinuation data were taken from placebo- and active-controlled trials identified in a systematic literature review and mixed-treatment comparison. Utility data were based on EQ-5D data.

Main outcome measures:

Additional symptom-control months (SCMs), defined as the amount of time at a response level of 30% or less, and quality-adjusted life-years (QALYs) over a 2-year time horizon.

Results:

For every 1000 patients, first-line duloxetine resulted in an additional 665 SCMs and 12.3 QALYs, at a cost of $582,911 (equivalent to incremental cost-effectiveness ratios [ICERs] of $877 per SCM and $47,560 per QALY). Second-line duloxetine resulted in an additional 460 SCMs and 8.7 QALYs, at a cost of $143,752 (equivalent to ICERs of $312 per SMC and $16,565 per QALY).

Limitations:

Response data for TCAs are limited to 30% improvement levels, reported trials are small, and have low placebo response rates. The model necessarily assumes that response rates are independent of placement in the treatment sequence.

Conclusions:

The results suggest that the introduction of duloxetine into the standard treatment sequence for fibromyalgia not only provides additional patient benefits, reflected by time spent in pain control, but also is cost effective when compared with commonly adopted thresholds.     

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States

Abstract

Objective:

To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV?+?r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy.

Methods:

A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts.

Limitations:

The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV?+?r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained <$50,000/QALY when these values were varied in sensitivity analyses.

Results:

ATV?+?r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs ($275,986 vs. 269,160). ATR?+?r patients had lower rates of AIDS (19.08 vs. 20.05 cases/1,000 patient-years), OIs (0.44 vs. 0.52), diarrhea (1.27 vs. 6.26), and CHD events (5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25). ATV?+?r added 0.26 QALYs at a cost of $6826, for $26,421/QALY.

Conclusions:

By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV?+?r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (<$50,000/QALY) compared with LPV/r.     

Cost-effectiveness analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective.

Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150?mg and 300?mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses.

Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations.

Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.     

Longitudinal analysis of healthcare costs: a case study of patients with major depressive disorder treated with duloxetine

Abstract

Objective:

To develop and apply a longitudinal model that adjusts for pre-treatment covariates to examine the trajectory of healthcare costs in duloxetine patients with major depressive disorder (MDD).

Methods:

Retrospective healthcare cost data from Thomson Reuters Marketscan® Database included 10,987 patients with MDD, aged 18–64, receiving duloxetine at low (<60?mg/day), standard (60?mg/day), or high (>60?mg/day) initial doses. A linear mixed-effects model for repeated measures used dose, month, and dose*month as fixed effects and patient (dose) as a random effect, and adjusted for demographics, comorbidities, body system disorders, and prior medication history. Model goodness-of-fit was evaluated with R². Rates of change (slopes) were estimated from the fitted model and differences in the cost trajectory among dosing cohorts were tested using the F-test. Bootstrapping and propensity score (PS) stratification were conducted to provide sensitivity analyses.

Results:

Main effects and covariates were all significant (p?<?0.05). Adjustment by pre-treatment covariates greatly improved the model fit (R^2?=?0.43). The model revealed a significant increase in healthcare costs in the 6 months preceding and a significant decrease in the 6 months following duloxetine initiation for each initial dose cohort and the overall cohort (p?<?0.05). In both the pre- and post-treatment periods, the high initial-dose cohort had higher healthcare costs than standard or low initial-dose cohorts (p?<?0.05). Bootstrapping and PS stratification confirmed these test results.

Limitations:

The analyses performed here were based on non-randomized, observational data, and thus subject to potential biases due to unmeasured confounding.

Conclusions:

Longitudinal models, compared with conventional mean-based methods, provide better opportunities to assess changes in cost trajectory patterns around the time of changes in medical treatment. In insured patients with MDD started on duloxetine, healthcare costs increased before duloxetine initiation, perhaps signaling a clinical deterioration that led to a change in treatment strategy. Healthcare costs then decreased following duloxetine initiation.     

Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib

Abstract

Objective:

To estimate the cost-effectiveness (cost per additional life-year [LY] and quality-adjusted life-year [QALY] gained) of lenalidomide plus dexamethasone (LEN/DEX) compared with bortezomib for the treatment of relapsed-refractory multiple myeloma (rrMM) in Norway.

Methods:

A discrete-event simulation model was developed to predict patients’ disease course using patient data, best response, and efficacy levels obtained from LEN/DEX MM-009/-010 trials and the bortezomib (APEX) published clinical trial. Predictive equations for time-to-progression (TTP) and post-progression survival (PPS) were developed by identifying the best fitting parametric survival distributions and selecting the most significant predictors. Disease and adverse event management was obtained via survey from Norwegian experts. Costs, derived from official Norwegian pricing data bases, included drug, administration, monitoring, and adverse event management costs.

Results:

Complete or partial responders were 65% for LEN/DEX compared to 43% for bortezomib. Derived median TTP was 11.45 months for LEN/DEX compared to 5.15 months for bortezomib. LYs and QALYs were higher for LEN/DEX (4.06 and 2.95, respectively) than for bortezomib (3.11 and 2.19, respectively). The incremental costs per QALY and LY gained from LEN/DEX were NOK 247,978 and NOK 198,714, respectively, compared to bortezomib. Multiple sensitivity analyses indicated the findings were stable. The parameters with the greatest impact were 4-year time horizon (NOK 441,457/QALY) and higher bound confidence intervals for PPS (NOK 118,392).

Limitations:

The model analyzed two therapies not compared in head-to-head trials, and predicted results using an equation incorporating patient-level characteristics. It is a limited estimation of the costs and outcomes in a Norwegian setting.

Conclusions:

The simulation model showed that treatment with LEN/DEX leads to greater LYs and QALYs when compared to bortezomib in the treatment of rrMM patients. The incremental cost-effectiveness ratio indicated treatment with LEN/DEX to be cost-effective and was the basis of the reimbursement approval of LEN/DEX in Norway.     

Clinical comorbidities,treatment patterns,and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care

Abstract

Objective:

To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings.

Methods:

Using the LifeLink? Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n?=?826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods.

Results:

Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p?<?0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p?<?0.0001). There were significant increases (p?<?0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p?=?0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods.

Limitations:

Limitations of this study are typical of those associated with retrospective database analyses.

Conclusions:

Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.     

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic

Abstract

Purpose:

The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots.

Methods:

An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables.

Results:

Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates.

Conclusions:

PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.     

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium

Abstract

Objective:

To assess the cost-effectiveness of dabigatran etexilate (‘dabigatran’) vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF).

Research design and methods:

A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses.

Results:

In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses.

Limitations:

The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium.

Conclusion:

This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.     

Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Abstract

Objective:

With increasing healthcare resource constraints, it has become important to understand the incremental cost-effectiveness of new medicines. Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors and bone metastases. This study sought to determine the lifetime cost-effectiveness of denosumab vs ZA in this setting, from a US managed-care perspective.

Methods:

A lifetime Markov model was developed, with relative rate reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials involving patients with castration-resistant prostate cancer (CRPC), breast cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real-world SRE rates in ZA-treated patients were derived from a large commercial database. SRE and treatment administration quality-adjusted life year (QALY) decrements were estimated with time-trade-off studies. SRE costs were estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were included. Costs and QALYs were discounted at 3% annually. One-way and probabilistic sensitivity analyses were conducted.

Results:

Across tumor types, denosumab was associated with a reduced number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were $49,405, $78,915, and $67,931, respectively, commonly considered good value in the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively. Results were sensitive to drug costs and SRE rates.

Limitations:

Differences in pain severity and analgesic use favoring denosumab over ZA were not captured. Mortality was extrapolated from fitted generalized gamma function beyond the trial duration.

Conclusion:

Denosumab is a cost-effective treatment option for the prevention of SREs in patients with advanced solid tumors and bone metastases compared to ZA. The overall value of denosumab is based on superior efficacy, favorable safety, and more efficient administration.     

Cost-effectiveness of grass pollen subcutaneous immunotherapy (SCIT) compared to sublingual immunotherapy (SLIT) and symptomatic treatment in Austria,Spain, and Switzerland

Background: While specific immunotherapy (SIT) has been proven to be cost-effective for the treatment of allergic rhinitis compared to symptomatic treatment, there is a lack of European studies in which sublingual (SLIT) and subcutaneous (SCIT) immunotherapy were compared. The present analysis is focused on the cost-effectiveness of SCIT compared to SLIT and symptomatic treatment of grass pollen allergy in Austria, Spain, and Switzerland. It will address specific properties of the underlying healthcare systems.

Methods: The investigation is based on a previously published health economic model calculation. This was designed as a Markov model with pre-defined health stages and a duration of 9 years covering specific preparations for SCIT (Allergovit) and SLIT (Oralair). The effectiveness was assessed as symptom-score based quality-adjusted life years (QALYs). Additionally, total cost has been determined as well as the cost-effectiveness of SCIT. The robustness of model results was proved in further sensitivity analyses.

Results: With regard to the effectiveness of both SCIT and SLIT, preparations were dominant compared to pharmacological symptomatic therapy. Both strategies were associated with additional cost, but, combined with the results on effectiveness, both have to be regarded as cost-effective. A direct comparison of the SCIT (Allergovit) and SLIT (Oralair) showed lower total costs of SCIT vs SLIT for Austria, Spain, and Switzerland (€1,368 vs €2,012, €2,229 vs €2,547, and €1,901 vs €2,220) and superior effectiveness (SCIT =8.02 QALYs; SLIT =7.98 QALYs; and symptomatic therapy =7.90 QALYs).

Conclusion: In patients with allergic rhinitis, SIT offers cost-effective treatment options compared to symptomatic treatment. When comparing SCIT (Allergovit) and SLIT (Oralair), SCIT was dominant in terms of QALYs as well as costs, in particular due to a slightly higher patient compliance and lower drug costs.     

Cost-effectiveness of golimumab for the treatment of patients with moderate-to-severe ulcerative colitis in Quebec using a patient level state transition microsimulation

Objective: To conduct cost-effectiveness analyses comparing the addition of golimumab to the standard of care (SoC) for treatment of patients with moderate-to-severe ulcerative colitis (UC) who are refractory to conventional therapies in Quebec (Canada).

Methods: An individual patient state transition microsimulation model was developed to project health outcomes and costs over 10 years, using a payer perspective. The incremental benefit estimates for golimumab were driven by induction response and risk of a flare. Flare risks post-induction were derived for golimumab from the PURSUIT maintenance trial and extension study, while those for SoC were derived from the placebo arms of the Active Ulcerative Colitis Trials (ACT) 1 and 2. Other inputs were derived from multiple sources, including retrospective claims analyses and literature. Costs are reported in 2014 Canadian dollars. A 5% annual discount rate was applied to costs and quality-adjusted life-years (QALYs).

Results: Compared with SoC, golimumab was projected to increase the time spent in mild disease or remission states, decrease flare rates, and increase QALYs. These gains were achieved with higher direct medical costs. The incremental cost-effectiveness ratio for golimumab vs SoC was $63,487 per QALY.

Limitations: The long-term flare projections for SoC were based on the data available from the ACT 1 and 2 placebo arms, as data were not available from the PURSUIT maintenance or extension trial. Additionally, the study was limited to only SoC and golimumab, due to the availability of individual patient data to analyze.

Conclusion: This economic analysis concluded that treatment with golimumab is likely more cost-effective vs SoC when considering cost-effectiveness acceptability thresholds from $50,000–$100,000 per QALY.     

The cost-effectiveness of pregabalin in the treatment of fibromyalgia: US perspective

Abstract

Objective:

To evaluate the cost-effectiveness of pregabalin in the treatment of fibromyalgia in a US patient population.

Methods:

A decision-analytic model was developed comparing pregabalin 150?mg twice a day (BID) and pregabalin 225?mg BID to placebo, duloxetine, gabapentin, tramadol, milnacipran, and amitriptyline in patients with severe fibromyalgia (Fibromyalgia Impact Questionnaire score >59; pain score >6.5). The model estimated response rates for all treatments at 12 weeks based on three randomized trials with pregabalin and a systematic review of published randomized controlled trials. Response was categorized as ≥30% improvement in baseline pain score plus global impression of change rating of much improved or very much improved. After 12 weeks of treatment, responders to treatment entered a treatment Markov model in which response was maintained, lost, or treatment discontinued. The cost-effectiveness end-points were cost per responder at 12 weeks and 1 year. Resource use was estimated from published studies and costs were estimated from the societal perspective.

Results:

Over 12 weeks, total cost per patient was $229 higher with pregabalin 150?mg BID than placebo, whereas pregabalin 225?mg BID was $866 less costly than placebo. At 1 year, pregabalin was cost saving and more effective than placebo, duloxetine, tramadol, milnacipran, and gabapentin. Compared with amitriptyline, pregabalin was not cost-effective at both dosages, although when excluding old and methodologically weak studies of clinical effectiveness of amitriptyline, pregabalin 225?mg BID became cost saving and pregabalin 150?mg BID was cost-effective.

Limitations:

Comparisons between pregabalin and other active agents are based on indirect comparisons, not head-to-head trials, and so should be interpreted with caution. Limitations for comparators include an inability to access sub-group data, inconsistency of response definitions, inclusion of older trials, and absence of long-term studies.

Conclusions:

This model found pregabalin to be cost-effective in treating patients with severe fibromyalgia.     

Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data

Objective: To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+?CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective.

Methods: A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs.

Results: Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios.

Limitations: In the absence of long-term real-world data, the lifetime projection could not be validated.

Conclusions: Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients with Ph+?CML-CP who were resistant or intolerant to imatinib.     

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany

Abstract

Objectives:

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis.

Methods:

The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant’s perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses.

Results:

In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of ?€1142 (95%CI: ?€1255; ?€1038) and ?€54 (95%CI: ?€188; €85) and incremental QALYs of 0.015 (95%CI: ?0.025; 0.056) and 0.027 (95%CI: ?0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects.

Conclusion:

The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.     

Economic evaluation of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease patients not on dialysis in the United Kingdom

Abstract

Objectives:

To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK.

Methods:

A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature.

Results:

Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained.

Limitations:

While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model.

Conclusions:

Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.     

Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy

Abstract

Objective:

This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer’s perspective in Italy.

Methods:

An individual patient simulation model was used to project lifetime medical costs (payer’s perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis.

Results:

Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient’s lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY.

Conclusion:

The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.