title: Rituximab (MabThera) for aggressive non-Hodgkin's lymphoma: systematic review and economic evaluation.
abstract: OBJECTIVE
  To determine the clinical and cost-effectiveness of adding rituximab to the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy regime for adult patients with diffuse large B-cell lymphoma (DLBCL).
  
  
  METHODS
  Electronic bibliographic database.
  
  
  METHODS
  Comparative studies were selected for review if they addressed the clinical or cost-effectiveness of adding rituximab to CHOP in people aged at least 18 years with DLBCL. The internal validity of the study was assessed through the use of the validated Jadad scoring system. Data were abstracted into standardised data extraction forms. Costs were estimated through resource use data taken from the published trial and the unpublished sponsor submission. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to evaluate the cost-effectiveness of R-CHOP compared with CHOP alone for patients with DLBCL using data sources and methodology similar to the manufacturer's submission.
  
  
  RESULTS
  In the systematic review of effectiveness, one randomised controlled trial was identified. The study was, in most respects, methodologically rigorous and well conducted and the statistical evidence favoured the addition of rituximab to CHOP. The total cost of rituximab with CHOP (R-CHOP) and CHOP alone estimated from the model developed by ScHARR was 14,456 pounds and 5773 pounds, respectively, for patients aged 60 years and over, and 15,181 pounds and 7311 pounds for patients aged less than 60 years over a 15-year time horizon. The ScHARR model estimated that the addition of rituximab to CHOP generated an additional 0.82 QALY at an extra cost of 8683 pounds compared with CHOP alone therapy over a 15-year time horizon, a cost/quality-adjusted life-year (QALY) ratio of 10,596 pounds for patients aged 60 years or more. For patients aged under 60 years, 1.05 QALY were generated at an additional cost of 7870 pounds, a cost/QALY ratio of 7533 pounds. Assuming that the societal value of a QALY was 30,000 pounds then R-CHOP is cost-effective compared with CHOP in the treatment of DLBCL.
  
  
  CONCLUSIONS
  In the short term, the addition of rituximab to the CHOP regimen increased the likelihood of a complete-response by 20% without a significant rise in the risk of a serious adverse event in people aged 60 years or older. Over a 2-year follow-up period, the intervention reduced the risk of death, progression or relapse by 45% and reduced the risk of death by 47% in this population. There is no direct evidence for the clinical effectiveness of adding rituximab to CHOP in the treatment of DLBCL in those aged 18-59 years, although data from phase I and II trials confirm its safety and efficacy in a preclinical setting. The cost-effectiveness modelling presented here has shown that rituximab in combination with CHOP chemotherapy regimen is likely to be considered a cost-effective treatment for DLBCL when compared with the current standard treatment, CHOP chemotherapy only. Analysis of quality of life (QoL) in the area of NHL is limited and only one cost-utility analysis for the treatment of CHOP in NHL was identified. Both the SCHARR and the manufacturer's models utilised QoL utility scores from an unpublished data source. Further research within this area would help to improve the robustness of QoL utility analysis within DLBCL and also NHL as a whole. Further clinical trials might also establish whether R-CHOP may replace peripheral blood stem cell transplant in high-risk patients and whether the doses of chemotherapy in the elderly may be reduced if rituximab is added to less intensive regimens.
authors.affiliation: School of Health and Related Research, University of Sheffield, UK.
authors.forename: C
authors.initials: C
authors.lastname: Knight
authors.forename: D
authors.initials: D
authors.lastname: Hind
authors.forename: N
authors.initials: N
authors.lastname: Brewer
authors.forename: V
authors.initials: V
authors.lastname: Abbott
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000191:economics / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003520:Cyclophosphamide / Q000191:economics / Q000627:therapeutic use; D003625:Data Collection; D004317:Doxorubicin / Q000191:economics / Q000627:therapeutic use; D016527:Drug Costs / Q000706:statistics & numerical data; D019317:Evidence-Based Medicine; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000191:economics / Q000401:mortality / Q000473:pathology; D020380:Needs Assessment; D009367:Neoplasm Staging; D036102:Peripheral Blood Stem Cell Transplantation; D011239:Prednisolone / Q000191:economics / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards; D012307:Risk Factors; D000069283:Rituximab; D016019:Survival Analysis; D013673:Technology Assessment, Biomedical; D016896:Treatment Outcome; D026712:Value of Life; D014750:Vincristine / Q000191:economics / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone