Direct Costs Associated with Relapsed Diffuse Large B-Cell Lymphoma Therapies.

BACKGROUND: About one third of patients with diffuse large B-cell lymphoma (DLBCL) relapse after receiving first-line (1L) treatment of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Relapsed patients may then be eligible for second-line (2L) therapy. The study's objective was to examine health care use and costs among treated patients with DLBCL receiving 2L therapy versus those without relapse. MATERIALS AND METHODS: We analyzed Truven Health MarketScan® claims data between 2006 and 2015. Patients (≥18 years of age) had ≥1 DLBCL claim from 1 year before to 90 days after beginning 1L therapy, and comprised those without 2L treatment for ≥2 years (cured controls) versus those who initiated non-R-CHOP chemotherapy after discontinuing 1L therapy (2L cohort). 2L patients were further subgrouped: hematopoietic stem cell transplant (HSCT [yes/no]) and time of relapse (months between 1L and 2L): early (≤3), mid (4-12), and late (>12) relapse. The primary outcome was 1- and 2-year health care costs. Hospitalization rate and length of stay were also measured. RESULTS: A total of 1,374 patients with DLBCL received R-CHOP and fulfilled all criteria: 1,157 cured controls and 217 2L patients (87 early-relapse, 66 mid-relapse, 64 late-relapse). Twenty-eight percent of 2L patients received HSCT. Charlson Comorbidity Index/mortality risk was higher for 2L patients (4.2 [SD: 3.0]) versus controls (3.8 [2.6]; p = .039), as were yearly costs (Year 1: $210,488 [$172,851] vs. $25,044 [$32,441]; p < .001 and Year 2: $267,770 [$266,536] vs. $42,272 [$49,281]; p < .001). HSCT and chemotherapy were each significant contributors of cost among 2L patients. CONCLUSION: DLBCL is resource intensive, particularly for 2L patients. Great need exists for newer, effective therapies for DLBCL that may save lives and reduce costs. IMPLICATIONS FOR PRACTICE: This study identified multiple important drivers of cost in the understudied population of patients with diffuse large B-cell lymphoma (DLBCL) receiving second-line (2L) treatment. Such drivers included hematopoietic stem cell transplant (HSCT) and chemotherapy. Even though HSCT is currently the only curative therapy for DLBCL, less than one third of patients receiving 2L and subsequent treatment underwent transplant, which indicates potential underuse. The variation in chemotherapy regimens suggested a lack of consensus for best practices. Further research focusing on newer and more effective treatment options for DLBCL has the potential to decrease mortality, in addition to reducing the extensive costs related to therapy options such as transplant.

Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

BACKGROUND: Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. METHODS: Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. RESULTS: The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. CONCLUSION: R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

BACKGROUND: Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. OBJECTIVE: The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. METHODS: A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. RESULTS: Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. CONCLUSION: First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost savings and higher health benefits for the Spanish NHS.

Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy.

OBJECTIVE: This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent. METHODS: A Markov model was created to compare seven prophylaxis strategies: 1) primary prophylaxis (PP) with nivestim (biosimilar filgrastim) throughout all cycles of chemotherapy; 2) PP with nivestim during the first two cycles of chemotherapy; 3) secondary prophylaxis (SP) with nivestim; 4) PP with pegfilgrastim throughout all cycles of chemotherapy; 5) PP with pegfilgrastim during the first two cycles of chemotherapy; 6) SP with pegfilgrastim; and 7) no prophylaxis (NP). The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted. RESULTS: Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60%) when the willingness to pay (WTP) threshold is lower than US$10,000 per FN episode prevented. CONCLUSION: In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim) is cost-effective for reducing the risk of FN in patients receiving R-CHOP.

Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis.

BACKGROUND: A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS: A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS: RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS: RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon.

Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

BACKGROUND: Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. OBJECTIVES: To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. METHODS: We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. RESULTS: Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. CONCLUSIONS: MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives.

Cost and Resource Use of Pemphigus and Pemphigoid Disorders Pre- and Post-Rituximab.

BACKGROUND: Rituximab (RTX) is increasingly used for the treatment of pemphigus and pemphigoid disorders. The high cost of RTX frequently limits its use and access. OBJECTIVE: To determine the health system resources and costs associated with RTX treatment of pemphigus and pemphigoid. METHODS: Health system resources and costs attributed to a convenience sample of 89 patients with either pemphigus or pemphigoid were identified, quantified, and valued 6 months prior to and following RTX initiation between May 2006 and August 2012. Overall cohort costs and costs per patient were calculated (2013 Can$). RESULTS: The overall cohort cost for 6 months pre-RTX was $3.8 million and for 6 months post-RTX was $2.6 million. The average cost per patient decreased from $42,231 to $29,423 (30.3% decrease). The main cost driver was intravenous immunoglobulin. CONCLUSIONS: Our findings suggest that RTX is effective in reducing health system resources and the costs associated with the treatment of pemphigus and pemphigoid.

Cost-effectiveness analysis of two rituximab retreatment regimens for longstanding rheumatoid arthritis.

OBJECTIVE: Rituximab (RTX) is licensed for second-line treatment of rheumatoid arthritis (RA) after first tumor necrosis factor (TNF) inhibitor failure. RTX is generally administered intravenously at 1 gm 2 weeks apart, and the retreatment is scheduled at the time of clinical relapse (regimen 1). A more intensive regimen is proposed with a fixed full cycle after 6 months (regimen 2) if remission is not reached. A cost-effectiveness analysis (CEA) compared these 2 regimens of RTX administration in patients with longstanding RA based on data provided by an observational study. METHODS: An observational retrospective study was conducted on 102 patients, enrolled in 3 hospitals and followed for ≥12 months. Forty-seven patients followed regimen 1, while 55 patients followed regimen 2. A CEA based on a Markov model was conducted. A lifelong and social perspective was adopted. CEA was conducted for the entire cohort and for the 2 subgroups separately (patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide and failures to TNF inhibitors). RESULTS: Results for the overall sample show at 10, 20, and 30 years that regimen 1 is less costly and associated with a higher quality of life compared to regimen 2. Probabilistic sensitivity analysis at 10 years estimated a probability of 95.1% for regimen 1 to be cost effective given a willingness to pay of €35,000/quality-adjusted life year, while for seropositive patients and for TNF failures it was estimated to be 92% and 92.7%, respectively. CONCLUSION: In longstanding RA, cost effectiveness of RTX retreatment at clinical relapse was found to be at least equivalent to the more intensive regimen proposed.

Mapping from the Health Assessment Questionnaire to the EQ-5D: the impact of different algorithms on cost-effectiveness results.

BACKGROUND: Many algorithms exist for converting the Health Assessment Questionnaire (HAQ) score to utility in rheumatoid arthritis (RA). Different algorithms convert the same HAQ score to different utility values, and could therefore lead to different cost-effectiveness results. OBJECTIVE: To investigate the impact of different mapping algorithms within the same cost-effectiveness model. METHODS: We rebuilt an existing economic model that had previously been used for estimating the cost-effectiveness of second-line biologics in RA. We reviewed the literature to identify algorithms that converted the HAQ score to utility and incorporated them into the model. We compared the cost-effectiveness results using different algorithms, exploring the reasons behind the different results and the potential effect on reimbursement decisions. RESULTS: We identified 24 different algorithms that estimated utility on the basis of the HAQ score, age, sex, and pain. The incremental cost-effectiveness ratio for rituximab versus disease-modifying antirheumatic drugs varied between £18,407/quality-adjusted life-year and £32,039/quality-adjusted life-year, which we speculate could have changed the recommendations made by the National Institute for Health and Care Excellence. CONCLUSIONS: Using different algorithms to convert the HAQ score to utility affects the cost-effectiveness of second-line biologics for the treatment of RA. Using different algorithms in economic modeling for RA could lead health technology assessment bodies to make different reimbursement decisions.

[Is rituximab effective for induction of remission in lupus nephritis?]. / ¿Es efectivo el rituximab para la inducción de remisión en nefritis lúpica?

The combination of cyclophosphamide and steroids constitutes the standard treatment in lupus nephritis requiring immunosuppressive therapy. However, it is associated with important adverse effects, so there is interest in alternative immunosuppressors such as rituximab. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified 5 systematic reviews including 24 studies. We combined the evidence using summary of findings tables following the GRADE approach and concluded there is uncertainty about the effects of rituximab in lupus nephritis because the certainty of the evidence is very low, probably leads to important adverse effects, and has high cost. Rituximab should not be used outside the context of a clinical trial, or only in cases where other treatments have failed and there are no resource constraints.

Cost savings from anemia management with biosimilar epoetin alfa and increased access to targeted antineoplastic treatment: a simulation for the EU G5 countries.

AIM: We simulated the budget impact of biosimilar erythropoiesis-stimulating agent (ESA) in EU G5 countries. MATERIALS & METHODS: Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated. RESULTS: Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51. CONCLUSION: Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BACKGROUND: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. METHODS: We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). RESULTS: Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. CONCLUSIONS: Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.

[Cost per responder associated with romiplostim and rituximab treatment for adult primary immune thrombocytopenia in France]. / Coût par patient répondeur associé au traitement du purpura thrombopénique immunologique primaire par romiplostim et rituximab chez l'adulte en France.

PURPOSE OF THE STUDY: This analysis compared the response rates and cost per responder associated with romiplostim and rituximab in adult immune thrombocytopenia from the French National Health System payer perspective. METHODS: A decision analytic model was developed to estimate the cost per patient and per responder of treating adult immune thrombocytopenia patients with romiplostim versus rituximab over 6 months. A systematic literature review identified phase 3 randomized controlled trials. Published response rates were extracted (response definition: ≥50×10(9) platelets/liter). Resource utilization was based on French and international treatment guidelines, and clinical expert opinion. Unit costs were derived from literature and French reimbursement lists, and included the costs of routine physician visits, treatment administration, and emergency care. Non-responders incurred bleeding-related event costs. RESULTS: The literature review identified a phase 3 randomized controlled trial for romiplostim with a response rate of 83%. Due to a lack of phase 3 randomized controlled trials for rituximab, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. Romiplostim and rituximab were associated with similar treatment costs, with an estimated cost per patient for romiplostim of €17,456 and €17,068 for rituximab. Rituximab resulted in a 30% higher cost per responder (€27,308 for rituximab versus €21,031 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related hospitalization costs compared to rituximab. CONCLUSIONS: Due to its high efficacy leading to lower bleeding-related costs, romiplostim represents an efficient use of resources for adult immune thrombocytopenia patients in the French healthcare system.

Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time and motion study in the United Kingdom.

OBJECTIVE: Rituximab is part of standard therapy for many non-Hodgkin lymphoma (NHL) patients, and is usually administered as an intravenous (IV) infusion. A formulation for subcutaneous (SC) injection will be available from June 2014. A time and motion study was conducted to investigate the staff time and costs associated with administration of SC and IV rituximab. RESEARCH DESIGN AND METHODS: The time and motion study was conducted in three UK centers alongside a phase III trial of SC rituximab in patients with NHL (ClinicalTrials.gov identifier NCT01461928). Active healthcare professional (HCP) time spent on the preparation and administration of IV and SC rituximab was recorded and used to calculate the associated costs. RESULTS: Total active HCP time associated with administration of IV rituximab was 223.3 min (95% CI = 218.0-228.7), vs 48.5 min (95% CI = 45.5-51.6) for SC rituximab, a saving of 174.8 min (95% CI = 172.5-177.1) per session. Patient time in the treatment room was 263.8 min (95% CI = 236.6-294.3) for IV rituximab and 70.0 min (95% CI = 57.1-87.2) for SC rituximab, per session. The SC formulation reduced total mean staff costs by £115.17 (95% CI = 98.95-136.93) per session. Differing monitoring scenarios during infusion consistently showed time and cost savings for SC rituximab. LIMITATIONS: Study limitations include the non-interventional design and lack of statistical power, and the investigational nature of SC rituximab. The data collected did not account for patient and center characteristics and variability on active HCP time. CONCLUSIONS: SC rituximab was associated with reduced active HCP time and costs vs IV rituximab, as well as reduced patient time in the treatment room. Switching from IV to SC rituximab could increase treatment room capacity and patient throughput, as well as improving the patient experience.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

OBJECTIVES: On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS: Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. RESULTS: Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. CONCLUSION: Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios.

Modelling the cost effectiveness of rituximab in chronic lymphocytic leukaemia in first-line therapy and following relapse.

BACKGROUND: The efficacy and safety of adding rituximab to fludarabine and cyclophosphamide (R-FC) for the treatment of chronic lymphocytic leukaemia (CLL) has been demonstrated in two randomised trials: CLL-8 was conducted in previously untreated patients, and REACH was conducted in previously treated patients. In both trials, progression-free survival was increased in the R-FC treatment groups compared with the FC treatment groups. In CLL-8, overall survival was also significantly increased. OBJECTIVE: To develop an economic model to assess the cost effectiveness, from the Australian healthcare perspective, of rituximab when used as a treatment for both previously untreated and relapsed/refractory CLL. METHODS: A Markov model with three health states (unprogressed, progressed and death) was developed to extrapolate the trial results over a 15-year time horizon. A treatment algorithm was developed with Australian haematologists to inform the treatments to be modelled. The base-case compares up to three courses of six cycles of R-FC ('first-line' treatment) followed by three courses of post-progression salvage ('Salvage') treatment (including rituximab) with three courses of FC followed by three courses of Salvage treatment (excluding rituximab). Subsequent treatments are incorporated into the model by repeating the unprogressed and progressed health states for each treatment. Time-dependent transition probabilities for the model were estimated from an analysis of individual patient data from CLL-8 and REACH. Comparisons of the hazard rates for the CLL-8 and REACH trials enabled an assessment of the impact on the transitions of receiving the same regimen as the first or second treatment, and hence inform assumptions regarding transitions for third and subsequent treatments. Costs applied in the model were based on published Australian prices in 2009. RESULTS: The model predicts patients receive an average of approximately two courses of treatment, and the addition of rituximab results in an incremental gain of 0.94 quality-adjusted life-years (QALYs). The incremental cost associated with the addition of rituximab is A$40,268, and hence the cost per QALY gained (QALYG) is A$42,906. CONCLUSION: Rituximab, in combination with chemotherapy, when used multiple times throughout the treatment algorithm, appears to be cost effective for CLL from the Australian healthcare perspective, with a cost/QALYG within the range generally accepted as providing value.

Cost effectiveness of romiplostim for the treatment of chronic immune thrombocytopenia in Ireland.

BACKGROUND: Romiplostim, a thrombopoietin receptor agonist (TPOra), is a second-line medical treatment option for adults with chronic immune thrombocytopenia (ITP). Clinical trials have shown that romiplostim increases platelet counts, while reducing the risk of bleeding and, in turn, the need for costly rescue medications. AIMS: The objective of this study was to assess the cost effectiveness of romiplostim in the treatment of adult ITP in Ireland, in comparison with eltrombopag and the medical standard of care (SoC). METHODS: A lifetime treatment-sequence cost-utility Markov model with embedded decision tree was developed from an Irish healthcare perspective to compare romiplostim with eltrombopag and SoC. The model was driven by platelet response (platelet count ≥50 × 10(9)/L), which determined effectiveness and progression along the treatment pathway, need for rescue therapy (e.g. intravenous immunoglobulin [IVIg] and steroids) and risk of bleeding. Probability of response, mean treatment duration, average time to initial response and utilities were derived from clinical trials and other published evidence. Treatment sequences and healthcare utilization practice were validated by Irish clinical experts. Costs were assessed in for 2011 and included drug acquisition costs and costs associated with monitoring patients and management of bleeding, as available from published Irish reimbursement lists and other relevant sources. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Romiplostim treatment resulted in an average of 20.2 fewer administrations of rescue medication (IVIg or intravenous steroids) over a patient lifetime than eltrombopag, and 29.3 fewer rescue medication administrations than SoC. Romiplostim was dominant, with cost savings of 13,258 and 22,673 and gains of 0.76 and 1.17 quality-adjusted life-years (QALYs), compared with eltrombopag and SoC, respectively. Romiplostim remained cost effective throughout a variety of potential scenarios, including short-term TPOra treatment duration (1 year). One-way sensitivity analysis showed that the model was most sensitive to variation in the cost of IVIg and use of romiplostim and IVIg. Probabilistic sensitivity analysis showed that romiplostim was likely to be cost effective in over 90 % of cases compared with eltrombopag, and 96 % compared with SoC at a willingness-to-pay threshold of 30,000 per QALY. CONCLUSIONS: Use of romiplostim in the ITP treatment pathway, compared with eltrombopag or SoC, is likely to be cost effective in Ireland. Romiplostim improves clinical outcomes by increasing platelet counts, reducing bleeding events and the use of IVIg and steroids, resulting in both cost savings and additional QALYs when compared with current treatment practices.

Rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG's main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.