Intest Res.  2022 Jan;20(1):11-30. 10.5217/ir.2020.00155.

Use of thiopurines in inflammatory bowel disease: an update

• Singh A
• Mahajan R
• Kedia S
• Dutta AK
• Anand A
• Bernstein CN
• Desai D
• Pai CG
• Makharia G
• Tevethia HV
• Mak JW
• Kaur K
• Peddi K
• Ranjan MK
• Arkkila P
• Kochhar R
• Banerjee R
• Sinha SK
• Ng SC
• Hanauer S
• Verma S
• Dutta U
• Midha V
• Mehta V
• Ahuja V
• Sood A

• KMID: 2525069
• DOI: http://doi.org/10.5217/ir.2020.00155

Abstract

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Keyword

Inflammatory bowel disease; Azathioprine; Mercaptopurine; 6-Thioguanine; Developing countries

Figure

• 

  Fig. 1. Thiopurine metabolism. AZA, azathioprine; 6-MP, 6-mercaptopurine; 6-TU, 6-thiouric acid; 6-TIMP, 6-thioinosine monophosphate; 6-TXMP, 6-thioxanthinemonophosphate; 6-TGMP, 6-thioguanine monophosphate; 6-TGDP, 6-thioguanine diphosphate; 6-TGTP, 6-thioguanine triphosphate; TdGTP, deoxy-thioguanosine triphosphate; TdGMP, deoxy-thioguanosine monophosphate; 6-MMP, 6-methyl mercaptopurine; 6-MMPR, 6-methyl mercaptopurine ribonucleotides; 6-TG, 6-thioguanine; TPMT, thiopurine-S-methyltransferase; NUDT15, nucleoside diphosphate-linked moiety X-type motif 15; XO, xanthine oxidase; HGPRT, hypoxanthine-guanine phosphoribosyl transferase; GMPS, guanosine monophosphate synthetase; IMPDH, inosine monophosphate dehydrogenase; GAP, GTPase-activating protein.

• 

  Fig. 2. An approach to initiation and monitoring of treatment with thiopurines. aThere are no definite recommendations for testing of liver functions or pancreatic enzymes, but this maybe done along with the CBCs. CBC, complete blood count; LFT, liver function tests; RBS, random blood sugar; RFT, renal function tests; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; VZV, varicella zoster virus; EBV, Epstein-Barr virus; HPV, human papillomavirus; HAV, hepatitis A virus; Tdap, tetanus, diphtheria and pertussis; 6-MMPR, 6-methyl mercaptopurine ribonucleotide; 6-TGN, 6-thioguanine nucleotides; NUDT15, nucleotide diphosphate-linked moiety Xtype motif 15; TPMT, thiopurine-S-methyltransferase.

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