Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease

Introduction. Individuals with inflammatory bowel disease (IBD) have an increased risk of osteoporosis compared to the general population. We aimed to improve the osteoporosis screening rate in the IBD patient population of the gastroenterology (GI) fellows’ continuity clinics. Methods. Baseline preintervention data were collected on patients seen from July through September of 2018. Four simplified criteria for osteoporosis screening were extrapolated from 3 national guidelines. Among patients who met any of these criteria, we determined the baseline screening rate. Fellows were then educated with a didactic session and handout material, and a standardized template was incorporated into clinic notes. Following this intervention, screening rates were reassessed from December 2018 through February 2019. Results. During the preintervention phase, fellows saw 80 patients with IBD. Dual-energy X-ray absorptiometry (DEXA) scan was obtained in 44% of IBD patients who qualify for screening at the county hospital clinic compared to 21% of veterans’ clinic IBD patients. In the postintervention period, screening rates remarkably improved to 100% in the county hospital clinic and to 75% in the veterans’ clinic. Overall, the screening rate increased by 56% (P<0.001). Conclusions. A large percentage of IBD patients at risk for osteoporosis did not have appropriate bone mass density testing. Educating GI fellows and adding a template to clinic notes were effective in significantly improving the number of patients at risk of osteoporosis to receive appropriate screening test, a DEXA scan. Similar educational interventions should be considered for providers caring for IBD patients to prevent complications of osteoporosis in these patients.

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THERAPEUTIC DRUG MONITORING OF INFLIXIMAB AND ADALIMUMAB FOR DETECTION OF PATIENTS AT RISK OF LOSS OF RESPONSE IN INFLAMMATORY BOWEL DISEASE.

10.26226/morressier.57c5383cd462b80296c9b440 ◽

2016 ◽

Author(s):

Manuel Barreiro-de Acosta

Keyword(s):

Inflammatory Bowel Disease ◽

At Risk ◽

Therapeutic Drug Monitoring ◽

Bowel Disease ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Loss Of Response ◽

Patients At Risk ◽

Inflammatory Bowel

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The need for better preventative strategies for inflammatory bowel disease patients at risk of herpes zoster virus

Internal Medicine Journal ◽

10.1111/imj.13488 ◽

2017 ◽

Vol 47 (11) ◽

pp. 1263-1269 ◽

Cited By ~ 3

Author(s):

William A. Bye ◽

Miles P. Sparrow ◽

Susan J. Connor ◽

Jane M. Andrews ◽

Katie Ellard ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

At Risk ◽

Herpes Zoster ◽

Bowel Disease ◽

Herpes Zoster Virus ◽

Patients At Risk ◽

Inflammatory Bowel

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Are CMV-predictive scores in inflammatory bowel disease useful in clinical practice?

Zeitschrift für Gastroenterologie ◽

10.1055/a-1221-5463 ◽

2020 ◽

Vol 58 (09) ◽

pp. 868-871

Author(s):

Hedwig Störkmann ◽

Jürgen Rödel ◽

Andreas Stallmach ◽

Philipp A. Reuken

Keyword(s):

Inflammatory Bowel Disease ◽

At Risk ◽

Bowel Disease ◽

Predictive Value ◽

Prognostic Scores ◽

Cmv Infection ◽

Patients At Risk ◽

Inflammatory Bowel ◽

Low Incidence ◽

Delay In Treatment

Abstract Background Concurrent cytomegalovirus (CMV) in inflammatory bowel disease (IBD)-related colitis is an important scenario associated with high rates of colectomy and other morbidity. Due to the low incidence of CMV, testing of all patients is associated with an unacceptably high consumption of resources and delay in treatment. Therefore, several predictive scores have been developed to identify patients at risk for a CMV infection. Methods We performed a retrospective single center study in a German University hospital including all IBD patients with available data on CMV-PCR analysis in whole blood between 2010 and 2018 and evaluated 2 prognostic scores for CMV infection for their diagnostic accuracy. Results In the study, 907 patients with IBD and CMV-PCR were identified. Of them, 21 patients (2.3 %) had a positive CMV-PCR (≥ 1000 copies/mL), 14 of them in ulcerative colitis and 7 in Crohn’s disease. The Berlin Score identified 667 patients (73.1 %) as potentially CMV-positive, resulting in a positive predictive value of 2.5 % and a negative predictive value of 98.3 %. In contrast, the Münster Score identified 60 patients as potentially CMV-positive, resulting in a PPV of 20 % and an NPV of 99.4 %. Conclusions Scoring systems can help to identify patients at risk for a CMV infection and minimize resource consumption and delay in treatment. Due to low incidence, a 2-step-algorithm, consisting of the Münster Score followed by a CMV-PCR if the score indicates a CMV infection, is preferable.

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P280 Therapeutic drug monitoring of infliximab and adalimumab for detection of patients at risk of loss of response in inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.405 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S220-S221

Author(s):

J. Gonzalez-Lopez ◽

J.M. Giráldez-Montero ◽

R. Ferreiro ◽

A. Lorenzo ◽

M.J. Lamas ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

At Risk ◽

Therapeutic Drug Monitoring ◽

Bowel Disease ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Loss Of Response ◽

Patients At Risk ◽

Inflammatory Bowel

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Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine

Gastroenterology Research and Practice ◽

10.1155/2021/9970019 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Katarzyna Bąk-Drabik ◽

Piotr Adamczyk ◽

Justyna Duda-Wrońska ◽

Dominika Dąbrowska-Piechota ◽

Anna Jarzumbek ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Therapeutic Range ◽

Bowel Disease ◽

High Performance ◽

Thioguanine Nucleotide ◽

Patients At Risk ◽

Inflammatory Bowel ◽

The Mean ◽

Maintenance Of Remission ◽

High Doses

Introduction. Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. Result. Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively ( Chi − square test = 3.87 , p < 0.05 ). Conclusion. Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.

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P339 Assessment of DNA-thioguanine nucleotide identifies patients at risk of thiopurine-induced leukopoenia in inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.468 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S325-S326

Author(s):

X Zhu ◽

K Chao ◽

X Gao ◽

M Huang ◽

X D Wang

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Roc Curves ◽

Blood Samples ◽

Clinical Toxicity ◽

Thiopurine Therapy ◽

Thioguanine Nucleotide ◽

Patients At Risk ◽

Inflammatory Bowel ◽

The Impact

Abstract Background Thiopurine drugs plays an important role for immunosuppressive therapy in inflammatory bowel disease. The molecular mechanism of the thiopurine toxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to assess the impact of DNA-TGN levels on thiopurine-induced toxicity. Methods Patients over 18 years who were diagnosed with IBD and prescribed on thiopurines from February 2019 to August 2019 were recruited. All of them were genotyped with NUDT15 R139C before the thiopurine therapy. A novel assay was established to measure levels of DNA-TGN in blood leucocytes. The DNA-TGN and 6TGN levels were correlated with clinical toxicity. Results 185 patients with Crohn’s disease and 5 patients with ulcerative colitis were included in this study. DNA-TGN and 6TGN levels could be quantified in 229 patients’ blood samples. Thiopurine-induced leukopoenia (TIL) arose in 19 individuals with the median 6TGN level of 308.0 pmol/8×108 RBC which was not significantly different from the patients without TIL (p = 0.050). However, there was a significant association between DNA-TGN levels and TIL. Patients who developed TIL were identified with a higher DNA-TGN levels compared with those who did not (p = 0.00030, 456.9 (63.3–879.2) vs. 268.9 (45.6–916.8) fmol/μg DNA). The area under the ROC curves of the continuous DNA-TGN concentration to predict TIL was 0.75 (95% CI: 0.63~0.87) and almost 84% (16/19) of the TIL could be explained based on the DNA-TGN cut-off value of 343.9 fmol/μg DNA Conclusion This study shows that quantification of DNA-TGN levels can be applied to gauge thioprine therapy and avoid TIL after pre-genotyping NUDT15 R139C in inflammatory bowel disease patients.

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