Cost-Effectiveness of Obinutuzumab in Combination with Bendamustine Followed by Obinutuzumab Maintenance versus Bendamustine Alone in Treatment of Patients with Rituximab-Refractory Follicular Lymphoma in Norway.

AIMS: To evaluate the cost-effectiveness of obinutuzumab in combination with bendamustine followed by obinituzumab maintenance (Obin-Benda) compared to bendamustine alone (Benda) in patients with refractory follicular lymphoma (FL) in a Norwegian setting. METHODS: A three-state area-under-the-curve (AUC) model was developed. The states included were progression-free-survival (PFS), progressed disease (PD), and death. Each state had costs and utilities assigned to it. The pivotal phase III randomized controlled trial GADOLIN was used for clinical input in the model along with Norwegian cost estimates. The trial demonstrated that Obin-Benda improved overall survival (OS), with a hazard ratio (HR) of 0.67 (95% CI 0.47-0.96), and reduced the likelihood of progression or death (HR 0.52, 95% CI 0.39-0.69) compared to Benda. The model used EQ-5D data collected in the GADOLIN trial, with UK tariffs assigned to the EQ-5D scores. RESULTS: The total quality adjusted life-years (QALYs) for the patients on Obin-Benda were estimated to be 4.67, compared to 3.65 for Benda, while the total costs were estimated to be €98,849 and €51,570, respectively. Obin-Benda had an incremental gain of 1.02 QALYs compared to Benda, at an additional cost of €47,279. The estimated deterministic incremental cost-effectiveness ratio (ICER) was €46,438 per QALY gained, while the probabilistic ICER was €46,887 per QALY gained (95% CI €34,772-€59,443). The results were robust to changes in various sensitivity and scenario analyses. CONCLUSIONS: The cost-effectiveness threshold in Norway is not public, but based on previous decisions it is estimated to be up to approximately €89,000 per QALY (NOK 800,000). The results of the analysis indicate that obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance may be cost-effective compared to bendamustine alone in Norway.

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US.

AIMS: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G + B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective. MATERIALS AND METHODS: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial's refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty. RESULTS: G + B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR = 0.61-1.87); the incremental total cost was $58,100 (95% CR = $54,500-$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G + B was cost-effective at the $100,000 per QALY threshold. LIMITATIONS AND CONCLUSIONS: This US-based analysis suggests that treatment with G + B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.

Economic evaluation of obinutuzumab in combination with chlorambucil in first-line treatment of patients with chronic lymphocytic leukemia in Spain.

OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death. Survival time for the two treatments was modeled based on the results of CLL11 clinical trial and external sources. Each health state was associated with a utility value and direct medical costs. The utilities were obtained from a utility elicitation study conducted in the UK. Costs and general background mortality data were obtained from published Spanish sources. Deterministic and probabilistic analyses were conducted, with a time frame of 20 years. The health outcomes were measured as life years (LYs) gained and quality-adjusted life years (QALYs) gained. Efficiency was measured as the cost per LY or per QALY gained of the most effective regimen. RESULTS: In the deterministic base case analysis, each patient treated with GClb resulted in 0.717 LYs gained and 0.673 QALYs gained versus RClb. The cost per LY and per QALY gained with GClb versus RClb was €23,314 and €24,838, respectively. The results proved stable in most of the univariate and probabilistic sensitivity analyses, with a probabilistic cost per QALY gained of €24,734 (95% confidence interval: €21,860-28,367). CONCLUSION: Using GClb to treat patients with previously untreated CLL for whom full-dose fludarabine-based therapy is unsuitable allows significant gains in terms of LYs and QALYs versus treatment with RClb. Treatment with GClb versus RClb can be regarded as efficient when considered the willingness to pay thresholds commonly used in Spain.

Cost effectiveness of tiotropium in patients with asthma poorly controlled on inhaled glucocorticosteroids and long-acting ß-agonists.

BACKGROUND: A considerable proportion of patients with asthma remain uncontrolled or symptomatic despite treatment with a high dose of inhaled glucocorticosteroids (ICSs) and long-acting ß2-agonists (LABAs). Tiotropium Respimat(®) added to usual care improves lung function, asthma control, and the frequency of non-severe and severe exacerbations, in a population of adult asthma patients who are uncontrolled despite treatment with ICS/LABA. OBJECTIVE: This study estimated the cost effectiveness of tiotropium therapy as add-on to usual care in asthma patients that are uncontrolled despite treatment with ICS/LABA combination from the perspective of the UK National Health Service (NHS). METHODS: A Markov model was developed which considers levels of asthma control and exacerbations. The model analysed cost and quality-adjusted life-years (QALYs); sensitivity and scenario analyses were also conducted to test the robustness of the base case outcomes. All costs are given at 2012 prices. RESULTS: The model found that in this category of asthma with unmet need, add-on tiotropium therapy generated an incremental 0.24 QALYs and £5,238 costs over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of £21,906 per QALY gained. Sensitivity analysis suggested that findings were most dependent on the costs of managing uncontrolled asthma and the cost of treatment with tiotropium. CONCLUSION: In this modelled analysis of two clinical trials, tiotropium was found to be cost effective when added to usual care in patients who remain uncontrolled despite treatment with high-dose ICS/LABA. Further research should investigate the long-term treatment effectiveness of tiotropium.