Cost‐effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease

Abstract

Summary Background : Azathioprine is a useful agent in the management of inflammatory bowel disease. Its use is limited by its side‐effect profile. Marrow toxicity occurs in approximately 3.2% of patients and is known to be associated with diminished thiopurine methyltransferase enzyme activity resulting from genetic polymorphisms. Aim : To evaluate the cost‐effectiveness of screening for thiopurine methyltransferase gene polymorphisms prior to initiation of azathioprine therapy. Methods : Analysis of the literature was undertaken to calculate the expected frequency of leucopenia and its relationship with thiopurine methyltransferase polymorphisms in a model of theoretical inflammatory bowel disease patients. Decision analysis was then applied to assess the cost of a pre‐treatment genotyping strategy, taking account of direct costs and cost per life‐year saved. Results : In 1000 inflammatory bowel disease patients treated with azathioprine, 32 will develop myelosuppression and one will die because of this. Of those who develop myelosuppression during azathioprine therapy, 32% are attributable to lower thiopurine methyltransferase activity. Pre‐treatment genotyping costs £347 per life‐year saved for a 30 year old and £817 per life‐year saved for a 60 year old. This compares favourably with other health care technologies. Conclusion : The use of pre‐treatment screening for thiopurine methyltransferase polymorphisms in inflammatory bowel disease patients commencing azathioprine therapy represents good value for money.

6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial

“…Measurement of TPMT activity before treatment with AZA or 6-MP is therefore advisable and cost-effective (38 ). In the case of TPMT activity between 8 and 20 nmol/(mL Ery ϫ h), the standard AZA dose of 2.5 mg/kg/day should be used.…”

Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

“…Recently, TPMT and its genotype have been applied to predict the efficacy and toxicity of drugs, which can provide some guidance for clinicians and reduce the incidence of drug toxicity in Western countries [25][26][27][28][29] . Meanwhile, studies have shown that examining TPMT enzyme activity may decrease the overall medical cost in Europe and America [30,31] . Therefore, developing a study of TPMT polymorphisms and enzyme activity in Han nationality Chinese with IBD and clarifying the correlation between the efficacy and toxicity of drugs and TPMT will provide theoretical evidence for the clinical application of immunosuppressive agents, such as AZA.…”

Association of Inosine Triphosphatase 94C>A and Thiopurine S-Methyltransferase Deficiency with Adverse Events and Study Drop-Outs under Azathioprine Therapy in a Prospective Crohn Disease Study

“…Safety data (blood count, aspartate aminotransferase, alanine aminotransferase, pancreatic amylase, and lipase) were collected during regular visits at 1,4,8,12,16, and 24 weeks after the start of aza therapy. Adverse events were recorded throughout the study.…”