Cost-effectiveness Of Rituximab Research Articles

UK cost-utility analysis of rituximab in patients with rheumatoid arthritis that failed to respond adequately to a biologic disease-modifying antirheumatic drug

ABSTRACTObjective: To evaluate the incremental cost effectiveness of rituximab in patients with rheumatoid arthritis that failed to respond adequately to tumour necrosis factor-α inhibitors (biologic disease-modifying antirheumatic drugs; bDMARDs). A cost-utility model has been developed to simulate the long-term incremental cost and benefits of rituximab using data from clinical trials and registries.Methods: The model estimates the lifetime disease progression of up to 10 000 hypothetical rheumatoid arthritis (RA) patients that failed one bDMARD. It compares cost and outcomes of two treatment sequences, representing the current UK standard both with and without rituximab. The population characteristics match those of the Randomised Evaluation of Long-term Efficacy of rituximab in RA (REFLEX) phase III randomised control trial. Clinical outcomes were based on an indirect comparison of published American College of Rheumatology response rates, adjusted for differences in placebo. To estimate medical resource use, health assessment questionnaire (HAQ) scores were grouped into five categories with UK registry data informing the average cost for each category. Quality-adjusted life years (QALYs) gained were mapped from disease severity (HAQ scores).Results: Compared to a standard UK treatment sequence (assuming the sequential use of bDMARDs) the introduction of rituximab led to a QALY gain of 0.526 years. The incremental cost-effectiveness ratios (ICERs) based on total direct medical cost were £11 601. Adding rituximab to a treatment sequence with no sequential use of biologic generates an ICER of £14 690.Conclusion: Rituximab has lower average annual treatment costs compared to other bDMARDs and is a highly cost-effective treatment option for patients who have failed to respond adequately to one bDMARD. The cost per QALY gained of rituximab falls well below commonly accepted thresholds within the UK. Potential weaknesses of the model include the paucity of data on the efficacy of bDMARDs or non-biologic DMARDs when used as second-line options; the lack of consensus about the most appropriate therapy in patients who fail all available bDMARDs; probable underestimation of the non-drug related medical costs; indirect measurement of QALY gains with rituximab therapy; and the necessity of synthesising data from a number of clinical trials with different populations and study drugs.

Cost-effectiveness of rituximab in refractory cold agglutinin disease

Cold haemagglutinin disease (CHAD) is an uncommon condition frequently associated with B-cell lymphoproliferative disorders and is refractory to conventional treatments used in autoimmune haemolytic anaemia. Rituximab has been used in this condition with favourable and lasting responses. Cost has been a major limitation to its use in such indication. We present cost-effectiveness analysis of the use of rituximab in two patients with CHAD. Rituximab successfully controlled haemolysis in both cases of CHAD and was found to be cost-effective through reducing transfusion needs.

Cost-effectiveness of rituximab plus CVP for first-line treatment of advanced indolent lymphoma

6583 Background: The addition of rituximab (RTX) to CVP (cyclophosphamide, vincristine, prednisone) in the treatment of advanced follicular lymphoma increases median time to progression by 17 months (15 month v 32 months; p < 0.0001) (Marcus et al, Blood 2005). A societal cost-effectiveness analysis was performed to estimate projected lifetime clinical and economic implications of this treatment. Methods: The cost-effectiveness (CE) of RTX + CVP versus CVP was estimated for a 50 yr old patient. Kaplan-Meier estimates of progression-free and overall survival, up to 4 years, were obtained from the M39021 trial. After 4 years, transition rates from initiation of treatment to progression or death were assumed to be the same in both arms. The clinical and economic implications of relapse and its treatment were included in the model. Incremental costs associated with addition of RTX were estimated using Medicare reimbursement rates and published retail price data. Costs included drug and administration costs, adverse events, treatment of relapses, and end-of-life costs. Utility estimates were derived from the literature and a 3% discount rate was employed. Results: Projected mean overall survival is 1.5 yrs longer for patients assigned to RTX+ CVP versus only CVP (13.7 v 12.2 yrs). The addition of RTX to CVP is estimated to cost an additional $26,439 on average, with an expected gain of 0.85 year of quality-adjusted survival. Over a lifetime, the cost per QALY gained is $31,329. Sensitivity analyses revealed that the variables that most influenced cost-effectiveness were the time horizon (range: $18,800- $31,240) and the unit drug cost of RTX (range: $24,000-$38,000). Conclusion: The model estimates a cost-to-QALY gained ratio that is below that of many treatments used for oncology patients. The use of RTX + CVP for first-line treatment of advanced follicular lymphoma is projected to be cost-effective compared to CVP alone under a range of sensitivity analyses. No significant financial relationships to disclose.

Cost-effectiveness (CE) analysis of CHOP and rituximab for diffuse large B-cell lymphoma (DLBCL) in British Columbia (BC)

6623 Background: The BC Cancer Agency (BCCA) provides province-wide, population-based care. Outcomes are monitored to verify therapeutic effectiveness and justify funding for systemic treatment policies. The CE of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (CHOP-R) for DLBCL was compared to its predecessor, CHOP alone. Methods: This was a pragmatic population-based CE analysis based on the original cohort of advanced DLBCL patients described by Sehn et al (JCO 2005) who received either CHOP or CHOP-R between Sept 1999 and Aug 2002 (18-months pre and post availability of rituximab in BC) according to standard BCCA treatment policy at the time. The primary endpoint was CE in terms of life-expectancy (LE) at a median follow-up of 4 years (cost-per-life-year-gained). Costs were incorporated into a decision analysis including primary systemic therapy and downstream chemotherapy, radiotherapy, and stem-cell transplant (SCT). Actual incidence of each downstream therapy was converted to a probability for each group. Downstream therapy costs were then multiplied by these probabilities and added to the respective primary treatment costs. The CE analysis took the BCCA perspective which includes all direct costs for active cancer treatment, and hospitalization for SCT, but not ambulatory supportive care. Sensitivity analyses varying LE to the extremes of its 95% CI, modeling out to 15 years and discounting at 0, 3, and 5% were performed. Results: 292 patients were included and categorized to treatment received: 148 CHOP and 144 CHOP-R (median follow- up 5.4 and 4 years respectively). LE to 4 years was 30.18 months for CHOP and 39.44 for CHOP-R. OS at 4 years was 48.8% and 70.1% for CHOP and CHOP-R respectively (p<0.0001) Respective costs of primary and downstream therapy were $4,682 and $7,198 for CHOP versus $26,366 and $6,228 for CHOP-R. The incremental CE ratio at 4 years median follow-up was $26,844 CDN per life year gained. Results were robust across univariate sensitivity analyses conducted. Conclusions: At 4 years median follow-up, CHOP-R improves LE and appears to be economically attractive at conventional thresholds. CE is an increasingly useful tool for the BCCA in making decisions about new cancer therapies. No significant financial relationships to disclose.

The Cost-Effectiveness of Rituximab, Cyclophosphamide, Vincristine and Prednisolone (RCVP) Compared with CVP for the Treatment of Follicular Non-Hodgkin's Lymphoma (NHL) in the UK.

Background: A large phase III randomised control trial (Marcus et al, Blood 2005, 105;4) has demonstrated that rituximab plus CVP compared with CVP alone improved time to treatment failure (p<0.0001) and a trend towards overall survival benefit (p=0.06). No analysis has yet been published relating to long-term clinical outcomes and costs of adding rituximab as a first-line treatment. Cost-effectiveness (CE) analysis aims to evaluate the additional costs and patient benefits (expressed as quality adjusted life years – QALYs) of an intervention (RCVP) compared with an alternative intervention (CVP). Some healthcare systems have CE thresholds to judge if the incremental cost-effectiveness ratio (ICER) is within acceptable limits; these thresholds vary across countries.Aims: To estimate the long-term clinical outcomes, direct health-service costs and incremental CE of RCVP compared with CVP for the first-line treatment of patients with follicular NHL.Methods: A CE analysis was developed using a state-transition Markov model, which simulated the lifetime progression of follicular NHL patients. Baseline patient characteristics were assumed equal to those in the Marcus et al study, with a mean age of 53. The CE of RCVP was evaluated using an ICER, based upon the UK health-service perspective. The model starts from the time of receiving first treatment until death. Patients could be in one of 3 discrete health states: progression-free survival, progression or death. The risk of disease progression for RCVP and CVP patients was derived directly from the results of the Marcus et al study, based upon a median trial follow-up of 42 months. The risk of death following disease progression was based upon outcomes reported by a UK registry of second-line follicular NHL patients (n=249). Patient quality of life was incorporated within the analysis using utility scores for each health state from a survey of follicular NHL patients (n=165) who completed the EQ-5D questionnaire. Cost and QALYs were discounted at 3.5%. Costs for patient monitoring and drug costs for second-line and later treatments were taken from published literature. Second-line and later treatments were assumed equivalent in both arms of the model.Results: Over the lifetime of a patient rituximab as a first-line treatment strategy generated higher total costs, but greater QALYs, compared with CVP alone. The average lifetime health-service costs per patient were £20,347 ($37,650) and £9,977 ($18,462) per patient for RCVP and CVP, respectively. Life expectancy was estimated as 9.4 yrs for RCVP and 7.2 yrs for CVP (undiscounted). Average QALYs for RCVP and CVP were 5.7 and 4.5 per patient, respectively (undiscounted). The ICER (discounted) of RCVP compared with CVP was £8,290 ($15,340) per QALY. Although there is uncertainty associated with the progression of follicular lymphoma and treatment costs, the ICER did not exceed £21,500 ($39,784) despite a wide variation in each parameter used in the analysis.Conclusions: Rituximab in combination with CVP is a cost-effective treatment option for the first-line treatment of follicular NHL. The clinical advantages of RCVP compared with CVP alone are predicted to generate an increase in life expectancy and QALYs. The resulting ICER for RCVP is well within the UK threshold of CE.

Cost effectiveness of rituximab + CHOP chemotherapy vs. CEOP + radiation therapy for advanced stage diffuse large B cell non Hodgkins lymphoma

Cost effectiveness of rituximab + CHOP chemotherapy vs. CEOP + radiation therapy for advanced stage diffuse large B cell non Hodgkins lymphoma