Cost-effectiveness Of Rituximab Research Articles

A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of Rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING)

BackgroundMinimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults.Methods130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant.Trial RegistrationTURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Cost-effectiveness analysis of rituximab versus natalizumab in patients with relapsing remitting multiple sclerosis

IntroductionMultiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths of the nerve cells in the brain and spinal cord, which are responsible for communication, are destroyed and cause physical signs and symptoms. According to studies, anti-CD20 monoclonal antibodies have significant results in the treatment of this disease. Thus, the aim of the present study was to determine the cost-effectiveness of rituximab against natalizumab in the patients with RRMS in southern Iran in 2020.MethodsThis is an economic evaluation including cost-effectiveness analysis in which the Markov model with a lifetime horizon was used. The study sample consisted of 120 patients randomly selected from among those referred to the MS Association and the Special Diseases Unit of Shiraz University of Medical Sciences. In this study, the costs were collected from a societal perspective, and the outcomes were obtained in the form of Quality Adjusted Life Years (QALY) and the mean relapse rate. The TreeAge pro 2020 and Excel 2016 software were used for data analysis.ResultsThe comparative study of rituximab and natalizumab showed that the patients receiving rituximab had lower costs ($ 58,307.93 vs. $ 354,174.85) and more QALYs (7.77 vs. 7.65). In addition, the incidence of relapse by rituximab was lower compared to natalizumab (1.15 vs. 2.57). The probabilistic one-way sensitivity analysis showed the robustness of the results. The scatter plots also showed that rituximab was more cost-effective for the patients in 100% of the simulations for the threshold of < $ 37,641.Discussion and conclusionAccording to the results of this study, rituximab had higher cost-effectiveness than natalizumab. Therefore, it could be a priority for RRMS patients compared to natalizumab because it reduced treatment costs and increased effectiveness.

Cost-Effectiveness of Rituximab (Fixed Schedule vs Tailored Dose) Compared With Azathioprine Maintenance Therapy in Adults With Generalized Antineutrophil Cytoplasm Antibody-Associated Vasculitis in Colombia

ObjectivesAzathioprine has been the therapy of choice for the maintenance of remission in patients with antineutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis, but recent studies show that rituximab could be more effective. To evaluate the cost-effectiveness of azathioprine, fixed-schedule rituximab, and tailored-dose rituximab for ANCA-associated systemic vasculitis. MethodsA Markov model from the perspective of the Colombian healthcare system was designed with annual cycles and a 5-year time horizon, charting the following states: remission, minor relapse, major relapse, and death. The discount rate was 5%. Transition probabilities were obtained from a systematic literature review. The costs (1 US dollar = 2956 Colombian pesos in 2018) were estimated based on national drug registries and official fee manuals for procedures, along with other resources. The main outcomes were quality-adjusted life-years (QALYs) taken from the Tufts registry. Univariate and multivariate sensitivity analyses were performed. ResultsFinal costs were $1446 for azathioprine, $4898 for tailored-dose rituximab, and $6311 for fixed-schedule rituximab. QALYs gained were 3.18, 4.08, and 3.98, respectively. Rituximab was cost-effective (cost per incremental QALY gained: $4919, and $6865), and tailored-dose administration had a lower cost. Sensitivity analyses did not affect the results. ConclusionsTailored-dose rituximab was the most cost-effective treatment for ANCA-associated vasculitis. Azathioprine presented worse effectiveness and lower cost, and fixed-schedule rituximab was dominated by tailored-dose rituximab.

Rituximab for interstitial pneumonia with autoimmune features at two medical centres.

ObjectivesMany patients with interstitial lung disease (ILD) have autoimmune manifestations but do not meet criteria for a systemic rheumatic disease. A subset meets criteria for interstitial pneumonia with autoimmune features (IPAF) and have ILD requiring therapy. We conducted a multicentre observational study to examine the use of rituximab (RTX) in IPAF.MethodsPatients from Mass General Brigham (MGB) and University of Chicago Medicine (UCM) were included if they were ≥18 years old, met the 2015 classification criteria for IPAF and were treated with RTX. Clinical improvement was defined as improvement in four out of four domains at 1 year after RTX initiation: documented clinician global assessment; oxygen requirement; need for respiratory-related hospitalization; and survival.ResultsAt MGB, 36 IPAF patients (mean age 61 years, 44% female) were treated with RTX. At 1 year, 18 (50%) were clinically improved, 12 (33%) were stable, and 6 (17%) died from progressive respiratory failure. At UCM, 14 IPAF patients (mean age 53 years, 71% female) were treated with RTX. At 1 year, eight (57%) were improved, two (14%) were stable, three (21%) died from progressive respiratory failure, and one (7%) was lost to follow-up. Two patients experienced minor infusion reactions, and two patients discontinued therapy owing to adverse events (infections).ConclusionIn patients with IPAF treated with RTX at two medical centres, the majority (40 [80%]) demonstrated improvement/stability at 1 year. These findings call for prospective studies, including randomized clinical trials, to determine the risks, benefits and cost effectiveness of RTX in IPAF.

Improved Outcome of Newly Diagnosed Childhood Mature B-Cell Lymphoma/Leukemia with High Tumor Burden Treated with BFM95-Based Protocol Combining Rituximab: A Report from Shanghai, China

The Berlin-Frankfurt-Münster (BFM) based protocols have been wildly used in children with non-Hodgkin lymphoma (NHL) and leukemia for more than ten years in China. At the same time, rituximab has become a standard medicine in the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and relapsed or refractory B-cell NHL. In this study, we explored the efficacy of rituximab in childhood CD20 positive B-NHL and B-cell acute leukemia (B-AL).To explore the effect of rituximab in mature B-cell lymphoma (B-NHL)/mature B-cell leukemia ((B-AL) in children, this study included children and adolescents aged younger than 18 years with newly diagnosed CD20 positive, stage III/IV B-NHL/B-AL for treatment combining NHL-BFM95-based protocol with rituximab. A total of 4 injections with 375 mg/m2 rituximab each were administered intravenously after prephase V course at one day before the following 4 course of chemotherapy. Retrospective cases diagnosed with stage III/IV B-NHL/B-AL in our center were used as historical control. All of these patients were treated under NHL-BFM90 based protocol. Patient characteristics, event free survival (EFS), recurrence and mortality were analyzed.From April 2009 to December 2015, 46 patients were recruited and treated with rituximab combining BFM95-based protocol (R+BFM95 protocol). 23 cases diagnosed with stage III/IV B-NHL/B-AL from January 2005 to March 2009 treated with BFM90-based protocol. All patients followed till December 31, 2016. This study recruited 35 males and 11 females with an average age of 6.9 years who were treated with R+BFM95 protocol. Among the historical control of 23 patients treated with BFM90-based chemotherapy, 18 were males and 5 were females and the average age of our historical control was 7.2 years. Among patients treated with R+BMF95 protocol, the average duration of continuous complete remission (CR) was 3.6 years. Compared with patients treated with BFM90-based protocol, the 5-year event free survival (EFS) of patients under R+BMF95 was higher (83.7±5.7% vs 69.6%±9.6% in R+BMF95 and BFM90 respectively), however the difference was not statistically significant (P=0.1062). Among subgroups of our patients between patients treated with R+BMF95 and BFM90, the 5-year EFS of patients with stage III disease was 87.3±6.1% vs 77.8±9.8% (P=0.2998), stage IV subgroup was 72.7%±13.4% vs 40.0±21.9% (P=0.0878), respectively. Among patients whose LDH level were below 500 U/L at diagnosis, R+BFM95 protocol achieved 100% EFS during our follow-up, nevertheless the 5-year EFS of patients in this group was not statistically different from that of patients treated with BFM90 (92.3±7.4%, P=0.2994). Among patients had LDH >500 U/L at diagnosis, the 5-year EFS in R+BFM95 group was 77.2±7.7% and significantly higher than that of BFM90 group (40.0±15.5%, P=0.0048). In the patient group treated with R+BFM95, there were 2 (2/46, 4.3%) did not achieve CR. During the follow-up, recurrence occurred in 5 patients (5/46, 10.9%) including 2 partial remission (PR). Early death occurred in 1 patient (1/46, 2.2%) in the first course due to tumor lysis syndrome. Two cases with recurrence were treated with R-ICE regimen however remission did not occur. All patients with recurrent disease died. In the control patients treated with BFM90-based protocol, there were 3 (3/23, 13.0%) did not achieve CR. One patient did not respond to chemotherapy therefore received second-look operation however the pathology was positive and he died of disease progression. The other 2 patients give up treatment after 2 courses of chemotherapy. One patient (1/23, 4.3%) died in the first course because of sepsis. One patient with relapsed disease received R-ICE treatment however not achieved remission again. All patients with recurrent disease also died in BFM90 group.To summarize, our study demonstrated the feasibility of rituximab for Chinese children with B-NHL/B-AL. Rituximab improved the prognosis of Chinese B-NHL/B-AL children, especially among patients with LDH >500U/L. However, the limited number of patients and retrospective study design suggested further randomized trial with larger number of patients to confirm the efficacy, as well as cost-effectiveness of rituximab in childhood B-NHL/B-AL in China. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cost effectiveness of rituximab and mycophenolate mofetil for neuromyelitis optica spectrum disorder in Thailand: Economic evaluation and budget impact analysis.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory condition of the central nervous system. The extent of disability depends on the severity of the disease and the number of relapses. Although azathioprine is currently the main treatment for patients with NMOSD in Thailand, patients often relapse during its use. Hence, it is argued that there are other drugs that would be more effective. The purpose of this study is to evaluate, from a societal perspective and from the economic impact on Thailand's healthcare system, the cost utility of treatment with mycophenolate mofetil (MMF) and rituximab in patients resistant to azathioprine. The Markov model with a one-year cycle length was applied to predict the health and cost outcomes in patients with NMOSD over a lifetime. The results showed that rituximab exhibited the highest quality-adjusted life year (QALY) gains among all the options. Among the rituximab-based treatments, the administration of a rituximab biosimilar with CD27+ memory B cell monitoring proved to be the most cost-effective option. At the willingness-to-pay threshold of 160,000 Thai baht (THB), or 5,289 US dollar (USD), per QALY gained, the treatment exhibited the highest probability of being cost effective (48%). A sensitivity analysis based on the adjusted price of a generic MMF determined that the treatment was cost effective, exhibiting an incremental cost-effectiveness ratio of -164,653 THB (-5,443 USD) and a 32% probability of being cost effective. The calculated budget impact of treating patients resistant to conventional therapy was 1-6 million THB (33,000-198,000 USD) for the first three years, while after the third year, the budget impact stabilized at 3-4 million THB (99,000-132,000 USD). These data indicate that, in Thailand, treatment of drug resistant NMOSD with a rituximab biosimilar with CD27+ memory B cell monitoring or treatment with a generic MMF would be cost effective and would result in a low budget impact. Therefore, the inclusion of both the rituximab biosimilar and a generic MMF in the National Drug List of Essential Medicine for the treatment of NMOSD may be appropriate.

Cost Effectiveness of Rituximab As Adjunctive Therapy in Reducing Apheresis Procedures and Hospital Length of Stay in Relapsed Thrombotic Thrombocytopenic Purpura

Introduction: Rituximab at standard dosing (375 mg/m2 weekly for 4 weeks) is effective in preventing thrombotic thrombocytopenic purpura (TTP) relapse and is recommended as a therapy of choice along with plasmapheresis (PLEX) in the UK expert-based guidelines on TTP (category IB), although it is not yet universally viewed as standard of care. There is also emerging data for low dose rituximab (100 mg weekly for 4 weeks) in the treatment of relapsing TTP with mixed data on efficacy as compared to standard dose rituximab. With this in mind, we conducted a retrospective chart review to examine the financial cost of treating a patient hospitalized for a TTP relapse with rituximab, PLEX and steroids compared to PLEX and steroids only. The purpose of this study was to determine an average savings per patient of utilizing rituximab as an adjunctive agent in the inpatient setting.Methods: Chart records for patients admitted to a major academic center with a diagnosis of TTP, defined as laboratory and smear evidence of microangiopathy with ADAMTS13 level of 10% or less or evidence of microangiopathy in a patient with a prior established diagnosis of TTP, were reviewed. The clinical course of all patients including treatments received and length of stay (LOS) for each hospitalization was recorded. TTP relapse was defined as hospitalization for TTP more than 30 days after hospital discharge. An average hospital cost per patient with a relapsed episode of TTP was calculated utilizing average costs for LOS and for PLEX during their hospitalization for TTP relapse. The average wholesale price of a fixed dose of rituximab for one cycle (defined as four doses of 375 mg/m2) was utilized to calculate the total cost of rituximab treatment. A cost superiority determination per patient was calculated by comparing the total cost of relapsed TTP hospitalizations versus the cost of rituximab administered in the inpatient setting. All costs are listed in United States Dollar (USD).Results: A total of 28 patients spanning 25 years were hospitalized for a TTP exacerbation. The median age of these patients was 40.7 with ADAMTS13 level of 6.5% at diagnosis and 3.2% at relapse. Of 28 patients, 15 patients had relapsed TTP for a total of 50 hospitalizations. All 15 relapsed patients were treated with PLEX and steroids during every hospitalization. The average number of inpatient PLEX procedures performed on patients admitted for relapsed TTP was 7.1 with an average hospital LOS of 9.6 days. 13 of the 15 relapsed patients received a total of 15 cycles of rituximab while 2 patients did not receive any rituximab. Of the 13 rituximab-treated patients, 10 received one cycle of rituximab, with 9 achieving a sustained remission and the other patient experiencing a relapse of TTP that was not treated with any additional rituximab; 2 received a second cycle, with both achieving a sustained remission, although 1 had an allergic reaction during the second cycle that led to discontinuation of rituximab. In total, 11 of 15 episodes of relapsed TTP were treated with rituximab with 73% achieving a sustained remission over a median follow up time of 36 months.In our study cohort, use of rituximab would have led to a reduction in 182 total hospitalization days and 135 total PLEX procedures, yielding a cost savings of $59,918.40 per relapse of TTP. This would be offset by a cost of $30,894 for each cycle of standard dose rituximab, for a net cost savings of $29,024.40 per occurrence of TTP relapse treated with rituximab. A similar cost analysis utilizing low dose rituximab yielded a net cost savings of $55,582.40 per relapse of TTP, assuming similar efficacy of low and standard dose rituximab.Conclusions: The addition of rituximab to PLEX and steroids in treatment of relapsed TTP is more cost effective than PLEX and steroids alone, owing to the high efficacy of rituximab and the cumulative costs of PLEX and hospital LOS. This cost superiority of rituximab holds both for standard and low dose rituximab, assuming similar efficacy of the latter. Although not calculated in our analysis, administration of rituximab in the outpatient rather than inpatient setting would result in further cost savings. Therefore, from a cost efficiency standpoint, rituximab should be incorporated into treatment paradigms for relapsed TTP. DisclosuresNo relevant conflicts of interest to declare.

PCN26 - Cost-Effectiveness of Rituximab in the Treatment of Diffuse Large B-Cell Non-Hodgkin's Lyphoma Patients (Dlbcl) in China

PCN26 - Cost-Effectiveness of Rituximab in the Treatment of Diffuse Large B-Cell Non-Hodgkin's Lyphoma Patients (Dlbcl) in China

Cost-effectiveness of rituximab in addition to fludarabine and cyclophosphamide (R-FC) for the first-line treatment of chronic lymphocytic leukemia

The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was €17 979 per QALY (€15 773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.

Rituximab in combination with corticosteroids for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis: a NICE single technology appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of rituximab (Roche Products) to submit evidence of the clinical and cost effectiveness of rituximab in combination with corticosteroids for treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the manufacturer’s submission to NICE. The evidence was derived mainly from a double-blind, phase III, placebo-controlled trial of rituximab in patients with new or relapsed ‘severe’ AAV, which compared a rituximab treatment regimen with an oral cyclophosphamide treatment regimen. Intravenous cyclophosphamide is also commonly used but was not included in the pivotal trial. The evidence showed that rituximab is noninferior to oral cyclophosphamide in terms of induction of remission in adults with AAV and de novo disease, and is superior to oral cyclophosphamide in terms of remission in adults who have relapsed once on cyclophosphamide. The ERG concluded that the results of the manufacturer’s economic evaluation could not be considered robust, because of errors and because the full range of relevant treatment sequences were not modelled. The ERG amended the manufacturer’s model and demonstrated that rituximab was likely to represent a cost-effective addition to the treatment sequence if given after cyclophosphamide treatment.

Rituximab for the First-Line Maintenance Treatment of Follicular Non-Hodgkin’s Lymphoma

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.

Cost-Effectiveness of Rituximab As Maintenance Treatment for Relapsed Follicular Lymphoma: Results of a Population Based Study

AbstractAbstract 4277 OBJECTIVES:Effectiveness of rituximab maintenance treatment among patients with relapsed follicular lymphoma (FL) has been established in a randomised setting (EORTC20981 trial). Although the golden standard, results might not be generalisable to unselected real-world patient populations. Outcomes research was conducted to calculate real-world cost-effectiveness of second line rituximab maintenance compared to observation in FL patients in the Netherlands. METHODS:Two Dutch population-based registries, PHAROS and HemoBase respectively, collected information on patient characteristics, treatment, and resource utilisation on patients diagnosed with FL in the past 20 years. Patients responding to second line chemotherapy were included in the observation or maintenance group. A Markov model was applied to calculate real-world cost-effectiveness. RESULTS:Although 735 FL patients entered the registries, only 57 and 49 patients were eligible and included in the observation and maintenance group, respectively. Median age was 61 years and similar in both groups. Differences between the groups were found for second line treatment with rituximab (77% and 92% in the observation and maintenance group p<0.05) and years since diagnosis (p<0.01). Besides, the proportion of people with a partial response was higher in the observation group (60%) compared to the maintenance group (33%). The maintenance group showed higher 3-year overall survival (75% versus 63%) and longer time till next treatment (p<0.01). Compared to the trial, our real-world population was older and fewer patients were diagnosed with stage IV FL. Real-world prescription of rituximab was comparable to the trial although cycles were prescribed more frequent. Daily practice data combined with trial efficacy data resulted in cost-effectiveness ratios between € 3,614 and € 5,246 per life year gained and €3,555 and € 5,156 per quality-adjusted life year. CONCLUSIONS:Real-world FL patients were not identical to trial patients emphasising the importance of studying real-world data. Nevertheless, these data also suggest that rituximab is an effective treatment in daily life. However, analysing non-randomised groups is challenging. Careful interpretation is required since observed dissimilarities between the groups suggested the representation of different types of patients. Nevertheless, real-world cost-effectiveness for second line rituximab maintenance was favourable compared to other haematological treatments. Disclosures:Pompen:Roche Netherlands: Employment. Révil:Roche Netherlands: Employment.

Rituximab for the first-line treatment of stage III–IV follicular lymphoma (review of Technology Appraisal No. 110): a systematic review and economic evaluation.

Follicular lymphoma (FL) is a non-Hodgkin's lymphoma which typically presents when the disease is at an advanced stage. The majority of patients receive first-line therapy of rituximab in combination with chemotherapy, with two-thirds receiving cyclophosphamide, vincristine and prednisolone. The clinical and cost-effectiveness of other chemotherapies in combination with rituximab in first-line therapy is not known. To systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of rituximab (MabThera(®), Roche Products) in combination with chemotherapy, compared with chemotherapy alone, for the first-line treatment of symptomatic stage III-IV FL. A systematic review of literature and an economic evaluation were carried out. Key databases [including MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index to Nursing and Allied Health Literature (CINAHL); EMBASE; The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases; Science Citation Index (SCI); and BIOSIS], plus research registers and conference proceedings, were searched for relevant studies from inception up to October 2010. One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. The quality of included studies was assessed by one reviewer and checked by a second. A patient-level simulation model was developed to estimate the costs and quality-adjusted life-year (QALY) gains from the perspective of the UK NHS and Personal Social Services, with costs and benefits discounted at 3.5% annually. Four randomised controlled trials comparing rituximab plus chemotherapy (R-chemotherapy) with chemotherapy alone in untreated, symptomatic patients with stage III-IV FL were identified. R-chemotherapy compared with chemotherapy alone increased the likelihood of a response to treatment in all four trials, with no additional toxicity of clinical relevance. Overall response rates were significantly improved in all four trials, with a difference between the R-chemotherapy and chemotherapy arms of between 5% and 24%, respectively. Complete response rates were also improved, with a difference between the R-chemotherapy and chemotherapy arms of between 2% and 25%, respectively. Exploratory meta-analyses were conducted; the level of statistical heterogeneity was very high and thus we believe the response rates from the individual trials to be a more robust estimator of the efficacy of the specific R-chemotherapy regimens. Over a follow-up period of 4-5 years, R-chemotherapy significantly increased the overall survival rate compared with chemotherapy alone in three trials, although data for two trials were compromised owing to the use of additional treatments. The incremental cost-effectiveness ratio (ICER) for the addition of rituximab to CVP (cyclophosphamide, vincristine and prednisolone), CHOP (cyclophosphamide, doxorubicin/adriamycin, vincristine and prednisolone) and MCP [mitoxantrone, chlorambucil (Leukeran(®), Aspen) and prednisolone] was £7720, £10,834 and £9316 per QALY gained, respectively, when it was assumed that first-line rituximab maintenance was not used. A scenario analysis is also presented, assuming that responders to R-chemotherapy in first-line induction receive maintenance with rituximab, increasing the ICER to £14,959, £21,687 and £20,493 per QALY gained, respectively. These relate to the sources of data used for the effectiveness in first and second line and the assumed utility values; there is uncertainty about the effect of salvage treatment on patients who had been previously treated with an anthracycline regimen. There is uncertainty whether or not rituximab is as effective in second-line treatment when patients have been previously treated with rituximab. The results from four randomised trials comparing R-chemotherapy with chemotherapy alone showed an improvement in clinical effectiveness outcomes, with minimal clinically relevant additional adverse events or toxicity. The cost per QALY gained is estimated to be < £25,000 for all three comparisons under our base-case assumption and is considerably lower if first-line rituximab maintenance is not assumed. More data on patients pre-treated with rituximab and on the effect of first-line maintenance with rituximab is required for future work. The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of rituximab as maintenance therapy in patients with follicular non-Hodgkin lymphoma after responding to first-line rituximab plus chemotherapy

A recent phase III trial demonstrated that maintenance rituximab® therapy after response to first-line treatment with rituximab plus chemotherapy (R-chemo) increases progression-free survival (PFS) for follicular non-Hodgkin lymphoma (f-NHL). A cost-effectiveness analysis of R-maintenance versus observation was conducted from a US payer perspective to estimate PFS and overall survival (OS) over a representative patient's lifetime. Primary outcomes were cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Compared with observation, R-maintenance increased mean PFS by 1.50 years, OS by 1.21 years and QALYs gained by 1.11 years. The incremental cost of maintenance therapy was $38 545. The costs per LYG and QALY gained were $31 934 and $34 842, respectively. Within the limitations of modeling long-term outcomes, R-maintenance therapy in patients who received R-chemo for previously untreated f-NHL compared with observation alone after R-chemo for first-line treatment for f-NHL is cost-effective from the US payer perspective.

Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators’ data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer’s model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer’s base-case incremental cost-effectiveness ratio (ICER) changed from £15,593 to between £40,000 and £42,000 per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at £20,000/QALY (£30,000/QALY) if a reduction in survival advantage relative to the manufacturer’s base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.

Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.

The clinical effectiveness and cost-effectiveness of rituximab for the first-line treatment of chronic lymphocytic leukaemia: an evidence review of the submission from Roche

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rituximab for the first-line treatment of chronic lymphocytic leukaemia (CLL) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer's searches for clinical effectiveness and cost-effectiveness data were appropriate and included all relevant studies. The submission's evidence came from a single, unpublished, well-conducted randomised controlled trial (RCT) comparing rituximab in combination with fludarabine and cyclophosphamide (R-FC) with fludarabine and cyclophosphamide (FC) alone for the first-line treatment of CLL. There was a statistically significant increase in progression-free survival (PFS) with R-FC compared with FC alone {median 39.8 months vs 32.2 months; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.43 to 0.72]}. However, the initial significant treatment benefit for R-FC compared with FC for overall survival was not maintained at a slightly longer follow-up time [median 25.4 months; adjusted HR 0.72 (95% CI 0.48 to 1.09)]. Response rates, numbers of patients with event-free survival and duration of response all favoured treatment with R-FC. Additional evidence from a mixed-treatment comparison model indicated R-FC to be significantly superior to chlorambucil alone for both PFS and overall and complete response rates. The incidence of grade 3 or 4 adverse events was higher in the R-FC arm (77%) than in the FC arm (62%). Dose modifications were also more frequent in this arm, but this did not lead to differences in treatment discontinuation. Roche used a three-state Markov model (PFS, progressed and death) to model the cost-effectiveness of R-FC compared with FC and chlorambucil alone. The model used a cycle length of 1 month and a lifetime time horizon. The approach taken to modelling was reasonable and the sources and justification of estimates were generally sound. The base-case analysis produced an incremental cost-effectiveness ratio (ICER) of 13,189 pounds per quality-adjusted life-year (QALY) for R-FC versus FC, and 6422 pounds per QALY for the comparison of R-FC versus chlorambucil, suggesting that R-FC is cost-effective at normal willingness-to-pay thresholds. One-way sensitivity analyses produced a range of ICERs from 10,249 pounds to 22,661 pounds per QALY for R-FC versus FC, and 5612 pounds and 6921 pounds per QALY for R-FC versus chlorambucil. Probabilistic sensitivity analysis results matched the deterministic results very closely. However, the sensitivity analysis did not fully investigate the uncertainty associated with differential values across arms or with the structural assumptions of the model, and utility values were not drawn from an empirical study. The NICE guidance issued as a result of the STA states that: Rituximab in combination with fludarabine and cyclophosphamide (R-FC) is recommended as an option for the first-line treatment of chronic lymphocytic leukaemia in people for whom fludarabine in combination with cyclophosphamide (FC) is considered appropriate. Rituximab in combination with chemotherapy agents other than fludarabine and cyclophosphamide is not recommended for the first-line treatment of chronic lymphocytic leukaemia.

Cost-effectiveness of rituximab, fludarabine, and cyclophosphamide (R-FC) in patients with previously untreated chronic lymphocytic leukemia (CLL).

e16500 Background: R-FC significantly increases progression-free survival (PFS) compared to FC in previously untreated CLL (phase III trial ML 17102-CLL-8). A cost-effectiveness analysis was conduc...

Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness.

Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma's impacts on patient's productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.