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

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.

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

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.

scholarly journals Importance of 6-Thioguanine Nucleotide Metabolite Monitoring in Inflammatory Bowel Disease Patients Treated with Azathioprine

PRILOZI ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 73-79
Author(s):  
Kristina Pavlovska ◽  
Marija Petrushevska ◽  
Kalina Gjorgjievska ◽  
Dragica Zendelovska ◽  
Jasmina Tonic Ribarska ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Inflammatory Bowel Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
High Performance ◽  
Metabolite Concentration ◽  
Duration Of Treatment ◽  
Time Duration ◽  
Thioguanine Nucleotide ◽  
Inflammatory Bowel

Abstract The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD). The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease. Thirty-four patients were included in this study. Type of disease, gender, time duration of therapy and adverse effects were recorded. Metabolite concentration was determined by high performance liquid chromatography. Twenty-one percent of patients have experienced an adverse effect, with leucocytopenia most commonly occurring (42.9%). More adverse effects were registered when patients were treated with azathioprine in a period of less than 3 months in comparison to the group of patients that have been under therapy between 3-12 months and more than 12 months (p˂0.05). Most of the patients that presented any adverse effect had high 6-TGN concentration (>450 pmol/8x108 Er). The mean value of 6-TGN metabolite concentration in IBD patients treated with azathioprine was 437.46 pmol/8x108 Er ± 198.82 pmol/8x108. The time duration of azathioprine treatment did not have any significant impact on the achieved 6-TGN concentration (p>0.05).Twenty patients (58.9%) had achieved remission after therapy initiation with azathioprine. More alertness is recommended to clinicians towards patients in the first 3 months of the therapy. Our study demonstrated that higher 6-TGN concentration is associated with azathioprine toxicity.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

scholarly journals SAT0462 ASSESSMENT OF BONE MINERAL DENSITY IN INFLAMMATORY BOWEL DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1188.1-1188
Author(s):  
C. Daldoul ◽  
N. El Amri ◽  
K. Baccouche ◽  
H. Zeglaoui ◽  
E. Bouajina
Keyword(s):  
Bone Mineral Density ◽  
Inflammatory Bowel Disease ◽  
Bone Mineral ◽  
Bowel Disease ◽  
Mineral Density ◽  
Femoral Site ◽  
Significant Difference ◽  
History Of ◽  
Inflammatory Bowel ◽  
The Mean

Background:Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is considered as a risk factor of low bone mineral density (BMD). In fact, the prevalence of osteoporosis ranges from 17% to 41% in IBD patients. The possible contributing factors may include malabsorption, glucocorticoid treatment and coexisting comorbiditiesObjectives:The purpose of our work was to determine the frequency and the determinants of osteoporosis in patients with IBD and to assess whether there is a difference in BMD status between UC and CD.Methods:This is a retrospective study, over a period of 5 years (from January 2014 to December 2018) and including patients followed for IBD who had a measurement of BMD by DEXA. Clinical, anthropometric and densitometric data (BMD at the femoral and vertebral site) were recorded. The WHO criteria for the definition of osteoporosis and osteopenia were applied.Results:One hundred and five patients were collected; among them 45 were men and 60 were women. The average age was 45.89 years old. The average body mass index (BMI) was 25.81 kg/m2 [16.44-44.15]. CD and UC were diagnosed in respectively 57.1% and 42.9%. A personal history of fragility fracture was noted in 4.8%. Hypothyroidism was associated in one case. Early menopause was recorded in 7.6%. 46.8% patients were treated with corticosteroids. The mean BMD at the vertebral site was 1.023 g/cm3 [0.569-1.489 g/cm3]. Mean BMD at the femoral site was 0.920g/cm3 [0.553-1.286g / cm3]. The mean T-score at the femoral site and the vertebral site were -1.04 SD and -1.27 SD, respectively. Osteoporosis was found in 25.7% and osteopenia in 37.1%. Osteoporosis among CD and UC patients was found in respectively 63% and 37%. The age of the osteoporotic patients was significantly higher compared to those who were not osteoporotic (52.23 vs 43.67 years, p = 0.01). We found a significantly higher percentage of osteoporosis among men compared to women (35.6% vs 18.3%, p=0.046). The BMI was significantly lower in the osteoporotic patients (23.87 vs 26.48 kg/m2, p=0.035) and we found a significant correlation between BMI and BMD at the femoral site (p=0.01). No increase in the frequency of osteoporosis was noted in patients treated with corticosteroids (27.9% vs 21.6%, p=0.479). Comparing the UC and CD patients, no difference was found in baseline characteristics, use of steroids or history of fracture. No statistically significant difference was found between UC and CD patients for osteoporosis(p=0.478), BMD at the femoral site (p=0.529) and at the vertebral site (p=0.568).Conclusion:Osteoporosis was found in 25.7% of IBD patients without any difference between CD and UC. This decline does not seem to be related to the treatment with corticosteroids but rather to the disease itself. Hence the interest of an early screening of this silent disease.Disclosure of Interests:None declared

scholarly journals Endoscopic Stricturotomy Is an Efficacious Option for Management of Strictures in Patients With Inflammatory Bowel Disease

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Nabeeha Mohy-ud-din ◽  
Gursimran S Kochhar
Keyword(s):  
Inflammatory Bowel Disease ◽  
Success Rate ◽  
Bowel Disease ◽  
Chart Review ◽  
Common Complication ◽  
Technical Success ◽  
Technical Success Rate ◽  
Safe Technique ◽  
Inflammatory Bowel ◽  
The Mean

Abstract Background Strictures are a common complication for patients with inflammatory bowel disease. Endoscopic stricturotomy (ESt) is a novel procedure for treatment of these strictures. Methods A chart review was performed for patients with strictures who underwent ESt. Results Eleven patients were included in the study and the total number of strictures treated was 12. The mean length of the strictures was 10.25 ± 4.36 mm. Technical success was achieved in 92% (n = 11) of the procedures. Postprocedural bleeding occurred in 9% (n = 1) of patients, and none of the patients had complications of infection or perforation. Conclusions ESt is a safe technique with high technical success rate.

Predictors of Surgical Intervention in Patients with Inflammatory Bowel Disease

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Khaled Hamdy Abd El Megeed ◽  
Shereen Abou Bakr Saleh ◽  
Christina Alphonse Anwar ◽  
Ahmed Elkattary Mohamed Elkattary
Keyword(s):  
Inflammatory Bowel Disease ◽  
Surgical Treatment ◽  
Bowel Disease ◽  
Surgical Intervention ◽  
High Sensitivity ◽  
Medical Patients ◽  
Mayo Score ◽  
Calprotectin Level ◽  
Inflammatory Bowel ◽  
The Mean

Abstract Background Inflammatory bowel disease (IBD) is comprised of two major disorders: Ulcerative Colitis and Crohn’s disease. Ulcerative Colitis affects the colon, where as Crohn’s disease can involve any component of the gastrointestinal tract from the mouth to the perianal area. These disorders have somewhat different pathologic and clinical characteristics, but with substantial overlap; their pathogenesis remains poorly understood. Objective To determine & detect different predictors that help us to characterize patients with high probability of undergoing surgical intervention for inflammatory bowel diseases. Patients and Methods The present study was designed to detect & identify possible factors that can be used to predict surgical intervention in patients with IBD. The present study was a case control study that was conducted on 80 patients with inflammatory bowel disease (either controlled by medical treatment or needed surgical intervention as a part of disease control) who were recruited form Ain-Shams university hospitals and El Quabbary general hospital in Alexandria. In the present study, the mean age of the included patients was 36.67 ±8.5 years old and 50% of the patients were males. The mean age at the onset of the disease was 25.81 ±6.8 years old. Results In the present study, there were statistically significant differences between surgical and medical patients in terms of CDAI for CD (p &lt; 0.001) and Mayo score for UC (p &lt; 0.001). Surgical patients were more likely to have higher scores. CDAI and Mayo score were negative predictors of surgical treatment. CDAI score &gt; 287 and Mayo score &gt; 8.5 achieved high sensitivity and specificity for the detection of surgical treatment. In the present study, we found that there was statistically significant differences between surgical and medical patients in terms of Stool Calprotectin level. Surgical patients were more likely to have higher Stool Calprotectin level. Stool Calprotectin level was negative predictor of surgical treatment at a level of &gt; 341.5 microgm/gm with high sensitivity and specificity. Conclusion Surgical treatment is a common outcome in IBD. Certain clinical features and the extent of disease are risk factors for surgical intervention. Our study indicates that smoking, Chron’s disease, perianal disease, granulomas, higher severity scores, higher stool Calprotectin level, CRP, and ESR were associated with higher risks of surgical intervention. In addition, smoking, peri-anal disease, CDAI, Mayo score, Stool Calprotectin level, and CRP level were predictors of surgical treatment. The findings of our analysis have implications for practice, particularly in the promotion of preoperative individualized risk prediction. The ability to predict which patients will need surgery and target more intensive, early treatment to that group would be invaluable. Further research through large prospective cohort studies is needed to confirm our findings and conclusions.

scholarly journals Transition of Inflammatory Bowel Disease Patients from Pediatric to Adult Care: An Observational Study on a Joint-Visits Approach

2020 ◽  
Author(s):  
Antonio Corsello ◽  
Daniela Pugliese ◽  
Fiammetta Bracci ◽  
Daniela Knafelz ◽  
Bronislava Papadatou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Inflammatory Bowel Disease ◽  
Observational Study ◽  
Bowel Disease ◽  
Transition Process ◽  
Major Surgery ◽  
Adult Care ◽  
Inflammatory Bowel ◽  
The Mean

Abstract BackgroundTransition from pediatric to adult care of patients affected by Inflammatory Bowel Disease (IBD) is a critical step that needs specific care and multidisciplinary involvement. The aim of our study was to evaluate the outcome of the transition process of a cohort of IBD patients, exploring their readiness and the consequent impact on quality of life.MethodsThis observational study followed transitioned patients up for a minimum of 18 months after the beginning of transition process, from January 2014 to April 2019. Transition was carried-out through joint visits pediatricians and adult gastroenterologists. Clinical data before and after transition were collected. A subgroup of patients was submitted to an anonymous online questionnaire of 38 items drawn up based on the validated questionnaires TRAQ and SIBDQ within the first 6 months from the beginning of transition process.ResultsEighty-two patients with IBD were enrolled, with a mean age at transition of 20.2±2.7 years. Before transition, 40.2% of patients already had major surgery and 64.6% started biologics. At transition, 24% of patients were in moderate to severe active phase of their disease and 40% of them had already been treated with ≥ 2 biologics. The mean value of the TRAQ questionnaires was 3.4±0.5 and the mean score of SIBDQ was 53.9±9.8. A significant association was found between a TRAQ mean score > 3 and a SIBDQ > 50 (p=0.0129). Overall, 75% of patients had a positive opinion of the transition model adopted.ConclusionsA strong association has been found between TRAQ and SIBDQ questionnaires, showing how transition readiness has a direct impact on the quality of life of the young adult with IBD.

scholarly journals Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Archana Shubhakar ◽  
Bas C Jansen ◽  
Alex T. Adams ◽  
Karli R. Reiding ◽  
Nicholas T. Ventham ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Predictive Capacity ◽  
Cox Proportional Hazard Models ◽  
Independent Replication ◽  
Inflammatory Bowel ◽  
Treatment Escalation

Abstract A blood-based prognostic biomarker to guide clinical decision-making at diagnosis of inflammatory bowel disease (IBD) would be immensely helpful. We investigated a composite serum N-glycomic biomarker to predict future disease course in 244 newly diagnosed IBD patients. Forty-seven individual glycan peaks were analysed using ultra-high performance liquid chromatography identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio (HR) 25.9, p = 1.1×10− 12; 95% confidence interval (CI), 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded a HR of 5.1 (p = 1.1×10− 5; 95% CI, 2.54–10.1). These data demonstrate the predictive capacity of serum N-glycan biomarkers and represent a step towards personalized medicine in IBD.

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