Evaluation of the off‐label usage of rituximab in a large teaching hospital in New South Wales

Abstract

A retrospective review of patients receiving rituximab off label in a large teaching hospital was conducted between July 2002 and January 2006. The indication, dosing regimen, efficacy and cost of rituximab were evaluated. Rituximab was prescribed for three clinical indications; acute organ transplant rejection, post-transplant lymphoproliferative disease and autoimmune disease. On average, 600 mg of rituximab was prescribed weekly for 4 weeks, costing the hospital $108,739.37. We suggest an initial approval for a limited number of doses with subsequent approval dependent on improvement in predefined clinical or biochemical end-points. Furthermore, we suggest an Australia-wide central database be established to enable delineation of the optimal dosing schedule, as well as monitoring of clinical outcome.

Prospective data collection of off‐label use of rituximab in Australian public hospitals

“…Rituximab has subsequently become a major therapeutic agent in the management of several B‐cell malignancies and has subsequently been registered for use in refractory rheumatoid arthritis. In addition to these approved indications, there has been growing interest in the B‐cell depleting properties of rituximab in the management of a heterogeneous group of autoimmune and inflammatory diseases …”

“…Off‐label prescribing is common in hospitalised patients, with estimates of up to 70% of adults receiving at least one off‐label medication during an admission and even higher rates recorded for paediatric inpatients . The increasing use of high‐cost biologics, such as rituximab, for off‐label indications raises several important issues, including cost‐effectiveness, funding mechanisms and long‐term safety . We prospectively collected nationwide data on the use of off‐label rituximab within Australian public hospitals, with the view of providing essential information for national drug regulatory and funding bodies to assist in the development of governance models around off‐label use of high‐cost biological therapeutic agents.…”

“…In addition to these approved indications, there has been growing interest in the B-cell depleting properties of rituximab in the management of a heterogeneous group of autoimmune and inflammatory diseases. [3][4][5] Rituximab results in the death of CD20 expressing B cells by antibody-dependent cell-mediated cytotoxicity, complement-mediated lyses or apoptosis. 6 CD20 is expressed on the surface of B cells from the pre-B-cell stage through to memory B cells but not on antibodyproducing plasma cells.…”

Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection

“…Despite the absence of any trial data, and the fact that rituximab does not target the antibody-producing plasma cells which lack CD20, 1,2 there is increasing 'off label' use in the prevention and treatment of antibody-mediated rejection (AbMR) in kidney/solid organ transplantation, including ABO incompatibility. 4 A significant contributor to the growing use of rituximab has been the apparently low incidence of side-effects and infective complications. 5 However, reports are emerging of increased incidence of infections following rituximab in haematological malignancy, with viral and opportunistic infections occurring at a time distant from administration.…”

Treatment of severe pemphigus foliaceus with rituximab

“…Ongoing surveillance of patients treated with rituximab for pemphigus and other autoimmune diseases is required to monitor long‐term complications. A recent review of the increasing use of rituximab for off‐label indications in a large teaching hospital highlighted the need for a database to help determine optimal dosing regimens and to record clinical outcomes 8 …”