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Background The therapeutic indications for rituximab are: Hodgkin's lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis. Purpose The aim of this study was to review the off-label use of rituximab in our hospital. Materials and methods Retrospective study of rituximab in off-label indications from October 2009 to June 2011. Data collected: age, sex, diagnosis, posology, number of doses planned and administered and cost of treatment. Results Rituximab was used for 21 patients (76.1% women) with a mean age of 39.3 years (11-71). The indications were antisynthetase syndrome (dermatomyositis), autoimmune encephalitis, nephrotic syndrome, neoplastic cerebellar syndrome, pemphigus foliaceus, acquired haemophilia A, acute renal rejection (2), autoimmune thrombocytopenic purpura (ITP) (2), systemic lupus erythematosus (SLE) (5) and neuromyelitis optica (6). Posology varied according to the indication. SLE and antisynthetase syndrome: 1 g every 14 days, 2 doses. Nephrotic syndrome, ITP, pemphigus foliaceus, haemophilia A and neuromyelitis optica: 375 mg / m2 intravenous once weekly, 4 doses and in the last indication there is an option of retreatment with 2 doses of 1000 mg depending the CD19 count. Neoplastic cerebellar syndrome: 375 mg/m2 intravenous every 28 days, 4 doses. Acute humoral rejection: 500 mg (single dose) for 1 patient once weekly, 4 doses for the other patient. 14.2% of patients didn't start treatment with rituximab and 72.2% received the planned total doses. Only 1 patient received 2 doses as a retreatment for neuromyelitis optica. The off-label use of rituximab meant a cost of 90,638 €. Conclusions Rituximab is widely used in autoimmune pathologies as a therapeutic alternative in patients who have failed conventional treatment, although its use is not supported by large clinical trials. The high cost and its wide use warrant large randomised controlled clinical trials to demonstrate its efficacy.

Background Acquired haemophilia A is a very rare disease caused by the development of clotting factor VIII (FVIII) inhibitors, resulting in haemorrhage and bleeding episodes. This situation has been reported during interferon therapy for chronic hepatitis C virus (HCV) infection. To eliminate FVIII inhibitors, immunosuppressive therapy with corticosteroids and cytotoxic drugs is regarded as the mainstay of therapy. Purpose To describe a case of acquired haemophilia A refractory to conventional immunomodulatory therapy that has responded to rituximab. Materials and methods Patient clinical history was reviewed and the following laboratory investigations were collected: haemoglobin, platelets count, coagulation tests (prothrombin time (PT) and activated partial thromboplastin time (APTT)) and FVIII and inhibitor levels. Results A non-haemophilic 63 years old male patient with chronic HCV infection was receiving antiviral therapy with pegylated-interferon at 180 mcg weekly plus ribavirin at 400 mg twice daily. After 21 weeks of antiviral therapy, patient was admitted to hospital for a large haematoma in right lateral abdominal muscles, coagulopathy and acquired haemophilia. Haemoglobin and platelets count were decreased, PT was normal, APTT was increased, FVIII level was 0% and FVIII inhibitor level was 345 Bethesda units (BU). Immunosuppressive therapy with intravenous metilprednisolone and oral cyclophosphamide was started. After 4 weeks, a slight improvement in FVIII level and a decrease in inhibitors were obtained; for this reason, oral cyclophosphamide was replaced by intravenous rituximab. Patient received rituximab at 375 mg/m2 four once-weekly doses and oral prednisone at 30 mg twice daily. Before the second dose of rituximab, FVIII level was 25% and FVIII inhibitors level, 3 BU; coagulation tests were normalised and haemoglobin and platelets count remained diminished. Conclusions After failure of standard therapy, the use of rituximab in off label condition appears to be an effective option to eliminate FVIII inhibitors in patients with acquired haemophilia.

Background Few studies have been undertaken on off-label drug use in Spain since the introduction of new legislation in 2009 in which the responsibility for off-label use was transferred from the Spanish Agency for Medicines and Health Products to the physician. Purpose To analyse which clinical units requested off-label drugs more often, for what treatments and indications they were used, and to establish the economic impact this had on a Spanish university hospital. Materials and methods Descriptive observational study from October 2009 to December 2012. We included all individual requests for off-label drugs received in the pharmacy service. The request was submitted by physicians who indicated prior treatment received and the reasons deemed appropriate for the requested treatment. Individualised assessment reports were written with an analysis of efficacy, safety, convenience and cost, which were referred to the hospital’s medical administration to make the decision to authorise or deny their use. Results A total of 512 requests were analysed, of which 72.7% were for antineoplastics (372), followed by the musculoskeletal system with 8.2% (42). The most-requested drugs were bevacizumab with 13.3% (68) and rituximab with 8.2% (42) of requests. It was observed that the most frequent off-label indications were for glioblastoma with 7.8% (40) and breast cancer 5.3% (27) of requests. Requests for adult units represented 80.5% (412), being mostly oncology at 43.9% (181) and haematology with 15.5% of requests (64). Paediatric clinical units performed 9.5% (100) of requests, of which the most frequent were onco-haematology with 49% (49) and rheumatology with 11% (11). The cost of off-label drugs authorised was 4,938,808 € with a median cost per patient of 7,340 € [1,307 €, 16,728 €] and represented 3.03% of the total expenditure of the pharmacy service. Treatments that were rejected would have meant an expenditure of 1,656,644 € and this would have been 1.02% of drug spending. Conclusions Off-label drugs were requested mostly in the field of oncology and haematology. The authorised off-label drugs are very expensive. Unapproved treatments would have increased costs with theoretically minimal health benefits. No conflict of interest.