NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series

Drug Metab Pers Ther. 2020 Aug 24;35(4). doi: 10.1515/dmpt-2020-0128.

Abstract

Objectives: Azathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.

Case presentation: Here we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.

Conclusions: Our report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.

Keywords: NUDT15; azathioprine; polymorphism; thiopurine methyltransferase (TPMT).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune* / chemically induced
  • Anemia, Hemolytic, Autoimmune* / drug therapy
  • Anemia, Hemolytic, Autoimmune* / genetics
  • Azathioprine / adverse effects
  • Genotype
  • Humans
  • Leukopenia* / chemically induced
  • Methyltransferases / genetics
  • Purpura, Thrombocytopenic, Idiopathic* / chemically induced
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / genetics
  • Pyrophosphatases / genetics

Substances

  • Methyltransferases
  • Pyrophosphatases
  • Azathioprine