Ferent drugs are used in the management of steroid-dependent ulcerative colitis. Drugs used include established

May 29, 2018

Ferent drugs are used in the management of steroid-dependent ulcerative colitis. Drugs used include established agents, such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, and golimumab. If common treatments fail, colectomy may be performed [16]. Current guidelines recommend thiopurines as first-line therapy to spare steroids in steroid-dependent ulcerative colitis [3, 6]. Therefore, the thiopurine agents azathioprine and 6-mercaptopurine are used to sustain steroid withdrawal in patients with steroid-dependent ulcerative colitis [5]. Azathioprine is a purine analog that competitively inhibits the biosynthesis of purine ribonucleotides [17]. Azathioprine is the main therapy for steroiddependent patients in China, because vedolizumab and golimumab are not available, and adalimumab is not indicated for use in patients with ulcerative colitis. Furthermore, cessation of infliximab is still considered in clinical practice because of its high cost and fear of long-term side effects [18]. There is also a reduced response to infliximab, which may reach approximately 13 per year with uninterrupted scheduled maintenance therapy [19]. Fraser et al. reported that the remission rate was 87 in 346 ulcerative colitis patients who received more than 6 months of azathioprine treatment [10]. Another study demonstrated that the steroid-free remission rate was 59.1 in patients with steroiddependent or steroid-resistant ulcerative colitis treated with azathioprine [9]. The most common adverse event of azathioprine is leukopenia, which occurs in 3.8 of patients [20]. Other adverse events include hepatitis, infection, pancreatitis, and hair loss. Once absorbed into the plasma, azathioprine is nonenzymatically converted to 6-mercaptopurine. 6-Mercaptopurine can be metabolized to 6-methylmercaptopurine by the enzyme thiopurine methyltransferase (TPMT), to 6thiouric acid by the enzyme xanthine PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25679764 oxidase, and toZheng et al. Trials (2017) 18:Page 5 ofthe active metabolites of 6-thioguanine nucleotide. 6Thioguanine nucleotide is the active ribonucleotide of 6-mercaptopurine; it functions as a purine antagonist, resulting in immunosuppression and lymphocytotoxicity. A deficiency in TPMT may lead to preferential 6mercaptopurine metabolism into 6-thioguanine nucleotide, resulting in myelosuppression [21]. An apparent genetic polymorphism of TPMT is associated with TPMT enzyme deficiency. Despite a lower frequency of variant TPMT observed in Asian populations [22], lower starting doses of azathioprine are recommended in Asian populations than in white populations, along with close monitoring of complete blood count and liver function [13]. Chinese herbal medicine is a type of complementary and alternative medicine, and is often used in patients with inflammatory bowel BEZ235 biological activity Disease [8], especially in China. Dai et al. [23] analyzed 247 patients with ulcerative colitis. The Sutherland Disease Activity Index scores for patients treated with TCM and those treated with integrated TCM and Western medicine were significantly lower for both groups after treatment (P < 0.01). Sugimoto et al. used the Chinese herbal medicine QingDai to treat 20 patients with moderate ulcerative colitis. The rates of clinical response, clinical remission, and mucosal healing were 72 , 33 , and 61 at week 8, respectively [24]. Qing-Dai stimulates mucosal type 3 innate lymphoid cells to generate interleukin-22, which induces antimicrobial peptide and tight junction production, sug.