Sa1679 - Nudt15 Variant can Predict the Development of Azathioprine Induced Leucopenia and Allow Optimal Dosing in Indian Patients with Inflammatory Bowel Disease (IBD)

Banerjee, Rupa; Kanth, Ravi; Medaboina, Kavitha; Boramma, Ganesh Girish; Govardhan, Bale; Ua, Steffie; Mahalaxmi, M; Gaddam, Narender; Singarapu, Ajay Kumar; Sasikala, Mitnala; Duvvur, Nageshwar R.

doi:10.1016/s0016-5085(18)31503-8

Cited by 3 publications

(4 citation statements)

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“…TPMT polymorphisms are known to have an impact on thiopurine toxic metabolite (6‐MMP) as well as 6‐TGN levels and are therefore routinely tested for, prior to commencement of AZA, especially in Western countries 2,6,8,36,37 . Recently, quite a few studies have reported that detection of NUDT‐15 gene variant predicts thiopurine‐induced leukopenia better than TPMT gene variants in Asian IBD patients 26‐30 . Genetic and thiopurine metabolite testing may reduce apprehension in dose‐escalation in tolerant patients and dose‐adjustment or re‐initiation of AZA in patients who have experienced a dose‐dependent adverse effect of AZA in the near future.…”

Section: Discussionmentioning

confidence: 99%

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Long‐term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real‐world experience

Yewale¹,

Ramakrishna²,

Doraisamy³

et al. 2023

JGH Open

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Background and AimAzathioprine (AZA) forms the cornerstone for maintenance of sustained remission in inflammatory bowel disease (IBD). There is apprehension regarding the long‐term effectiveness and safety of AZA in IBD. We present our experience with AZA use and outcomes in a cohort of IBD patients followed up over a long period of time.MethodsRecords of 507 IBD patients under treatment at a single, tertiary care center in south India between 2013 and 2022 were evaluated retrospectively. Long‐term compliance, tolerance, clinical outcome at the point of last follow‐up, type and duration to the onset of adverse events, and subsequent amendment to treatment with regard to AZA were analyzed.ResultsOf 507 patients with IBD, 320 patients (207 Crohn's disease [CD], 113 ulcerative colitis [UC]) who received AZA were included. The median follow‐up was 41 months (interquartile range 15.5–77.5). Total duration of exposure was 1359 patient‐years with median usage of 33 months. Of the patients, 26.9% received AZA for >5 years. Mean initiation and maximum doses of AZA were 0.97 and 1.72 mg/kg/day. Among the participants, 20.6% experienced side effects, including myelotoxicity (7.2%) and gastrointestinal intolerance (5.6%). Six patients developed malignancy. Among the side effects, 39.4% of side effects were dose‐dependent. Among the patients, 38.1% had relapses requiring pulse corticosteroid therapy, and 16.2% had more than one relapse after commencement of AZA. AZA was continued till the last follow‐up in 76.5%. Among the patients, 49.7% (UC 51.3, CD 48.8) attained durable remission without biologics, and 5.3% continued to have active disease.ConclusionAZA is safe and effective in the long‐term in IBD. Effectiveness, tolerance, and compliance with AZA are well sustained beyond 5 years of usage and comparable between UC and CD.

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Section: Discussionmentioning

confidence: 99%

“…NUDT‐15 hydrolyses thiopurine effector metabolites and its mutations lead to accumulation of these metabolites and resultant cytotoxicity. The incidence of these polymorphisms varies significantly across different ethnicities, with NUDT‐15 mutation being more prevalent in IBD patients with an Asian ancestry 26‐30 …”

Section: Introductionmentioning

confidence: 99%

Long‐term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real‐world experience

Yewale¹,

Ramakrishna²,

Doraisamy³

et al. 2023

JGH Open

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“…However, with increasing research in a variety of ethnicity, there is increased interest in other important variants, such as nudix hydrolase 15 ( NUDT15 ), which is found at a higher frequency in Asian populations 110,111 . Indeed, in populations with a higher prevalence of NUDT15 SNVs it has been shown to be a better predictor of neutropenia than TPMT genotyping 111,112 . Banerjee et al reported 19‐ and 21‐fold higher risks of leucopenia and neutropenia, respectively, in patients expressing the variant NUDT15 c.415C>T (rs116855232) 112 .…”

Section: Clinical Implementation Of Pgxmentioning

confidence: 99%

“…Indeed, in populations with a higher prevalence of NUDT15 SNVs it has been shown to be a better predictor of neutropenia than TPMT genotyping 111,112 . Banerjee et al reported 19‐ and 21‐fold higher risks of leucopenia and neutropenia, respectively, in patients expressing the variant NUDT15 c.415C>T (rs116855232) 112 . It is suggested in patients that are NUDT15 IM, a dose reduction or alternative treatment should be considered 51 …”

Section: Clinical Implementation Of Pgxmentioning

confidence: 99%

Implementation of pharmacogenomics: Where are we now?

Medwid

Kim

2022

Brit J Clinical Pharma

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Pharmacogenomics (PGx), examining the effect of genetic variation on interpatient variation in drug disposition and response, has been widely studied for several decades. However, as cost, as well as turnaround time associated with PGx testing, has significantly improved, the use of PGx in the clinical setting has been gaining momentum. Nevertheless, challenges have emerged in the broader clinical implementation of PGx. In this review, we will outline current models of PGx delivery and methodologies of evaluation, and discuss clinically relevant PGx tests and associated medications. Additionally, we will describe our approach for the broad implementation of pre‐emptive DPYD genotyping in patients taking fluoropyrimidines in Ontario, Canada, as an example of clinically actionable PGx testing with sufficient clinical evidence of patient benefit that can become a new standard of patient care. We will highlight challenges associated with PGx testing, including a lack of diversity in PGx studies as well as general limitations that impact the broad adoption of PGx testing. Lastly, we examine the future of PGx, discussing new clinical targets, methodologies and analysis approaches.

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Optimising management strategies of inflammatory bowel disease in resource-limited settings in Asia

Mak

Pal

et al. 2020

The Lancet Gastroenterology & Hepatology

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Sa1679 - Nudt15 Variant can Predict the Development of Azathioprine Induced Leucopenia and Allow Optimal Dosing in Indian Patients with Inflammatory Bowel Disease (IBD)

Cited by 3 publications

References 0 publications

Long‐term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real‐world experience

Long‐term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real‐world experience

Implementation of pharmacogenomics: Where are we now?

Optimising management strategies of inflammatory bowel disease in resource-limited settings in Asia

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