Hepatitis B, Rituximab, Screening, and Prophylaxis: Effectiveness and Cost Effectiveness

Abstract

An important role of medical journals is to communicate information between stakeholder groups. These communications may be between researchers about findings that inform future research; results of phase I-II trials in Journal of Clinical Oncology (JCO) exemplify this purpose. Alternately, communications between practitioners can advise about implementing clinical practices, such as with narrative reviews and case-based manuscripts including JCO’s Oncology Grand Rounds, which provide guidance to practitioners. Communications from investigators to practitioners and policy makers include results of randomized controlled trials (RCTs) and systematic reviews. These communications inform decisions about managing individual patients and health care delivery policies. For policy determination, economic evaluations also have an important role. Implicit in conducting an economicanalysis ispriordemonstrationthattheinterventioniseffective. With this knowledge in hand, understanding economic ramifications of adopting an intervention may be very helpful: a central premise is that resourcesarescarceanddecisionsaboutalternativesareassociatedwithan opportunity cost because resources used for one purpose are unavailable for another use. JCO has provided guidance to researchers intending to submit a report of an economic analysis; high priority is given to analyses that affect decisions about adoption. In the article that accompanies this editorial, Zurawska et al provide a cost-effectiveness analysis assessing hepatitis B virus (HBV) screening before administering rituximab, cyclophosphamide,doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy to patients with diffuse large B-cell lymphoma (DLBCL). Their analysis links data demonstrating that when treated with R-CHOP, patients with DLBCL who are chronically infected with HBV can experience reactivation of HBV infection leading to acute hepatitis with consequences including morbidity associated with infection, compromise of chemotherapy delivery that might result in morbidity and mortality associated with suboptimal control of lymphoma, and death from fulminant hepatitis. This analysis assumes that effective strategies for screening and prophylaxis exist. The authors conclude that routine screening of all patients with DLBCL before chemotherapy is cost effective because, in comparison with alternatives, it is least costly and associated with superior 1-year survival. Setting aside the above assumptions and implications of the authors’conclusions, thisanalysis followspublishedrules forreportingan economic evaluation, as the study question includes clear alternatives (screen all, screen high-risk patients, screen none), the perspective of the analysis is provided (a Canadian province’s Ministry of Health and Long Term Care), costing appears to be comprehensive and credibly valued, and results were provided using incremental differences and with associated sensitivity analyses. A minor criticism is that conclusions may be overstated because the differences in costs and life-years saved between alternatives are marginal; stating that a screen-all strategy falls well within standard benchmarks for cost effectiveness would be a more conservatively stated conclusion. Screening all patients with DLBCL would be expected to be even more cost effective in jurisdictions with HBV prevalence rates that exceed those observed in Canada. At issue is how this economic analysis informs decisions to adopt a strategy to screen all patients with DLBCL for HBV. Other information helps to frame Zurawska et al’s conclusions. First, the problem is important:reactivationofHBVinpatientswithcancerreceivingchemotherapy is recognized and available data show that this risk is increased withthemoreprofoundimmunosuppressionassociatedwithlymphoma and treatment that includes steroids and now rituximab. Second, authors of a meta-analysis that included two RCTs and additional observational data concluded that while these data are associated with important limitations, a reasonable interpretation is that prophylaxis with lamivudine is preferred over a no-treatment approach when patients with cancer testing positive for hepatitis B surface antigen (HBsAg) are treated with chemotherapy. Third, synthesis of these two points has resulted in publication of numerous guidelines recommending screening for HBV and antiviral prophylaxis for cancer patients with positive testing (Table 1), especially when rituximab is used to treat lymphoma. Screening has also been recommended for patients who are to receive rituximab for treatment of benign conditions. Finally, despite these guidelines, practice variation exists with poor uptake of these recommendations: Zurawska et al cite data reporting routine screening in their geographic region of only 14% of patients with cancer who are to receive chemotherapy, an Australian survey that included oncologists who treat lymphoma reported that 47% never screen for HBV before initiating chemotherapy and in a North American teaching hospital only 36.6% of patients treated with rituximab between 1997 and 2009 had HBV testing although rates increased to 67.4% after introduction of guidelines. A previous survey has suggested that one reason for variable adoption may be concern about cost effectiveness. Zurawska et al’s conclusions might thus promote adoption of screening for patients with lymphoma, especially if concerns about cost effectiveness were accentuated by a recent publication in JCO by Day et al, which deemed routine prechemotherapy screening of patients with solid JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 26 SEPTEMBER 1