P670 Usefulness of monitoring the concentration of azathioprine metabolites in the children with inflammatory bowel disease and autoimmune hepatitis

Abstract Background Azathioprine (AZA) is an immunosuppressive drug, which is metabolised in the liver and kidneys into 6-thioguanine- the form responsible for the therapeutic effect. Despite its anti-inflammatory, antibacterial and immunomodulating properties, azathioprine has also dose-related side effects, such as bone marrow suppression, liver damage and pancreatitis. The purpose of this study was to assess the usefulness of monitoring the concentration of azathioprine metabolites: 6-tioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in the group of paediatric patients with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Methods The clinical data of 46 paediatric patients (24 girls) with IBD and AIH, aged 8–17 years, hospitalised in the Department of Gastroenterology, who had undergone a blood examination for AZA metabolites concentration, were analysed. Results Initial mean dose of azathioprine was 1.23 mg/kg/day in IBD and 1.16 mg/kg/day in AIH. In 30% of patients, the concentrations of 6-TG and 6-MMP were within the normal range. Forty-eight per cent of patients required a dose change due to: elevated 6-TG concentration (32.6%) or underdosage (15.4%). After modification the mean dose was 1.16 mg/kg/day in IBD and 0.85 mg/kg/day in AIH. In 10.7 % of patients, the concentrations of 6-TG and 6 MMP were below the proper range, in the same percentage of patients metabolites were undetectable. Conclusion In a significant number of cases monitoring the concentration of AZA metabolites indicated the necessity to reduce the dose of AZA allowing to achieve the therapeutic optimum and prevent serious side effects. Receiving undetectable concentration of metabolites is a sign of non-compliance. The final doses of AZA were found to be lower than the recommended doses. Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels is a good strategy that can be used to optimise IBD and AIH therapeutics.

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Therapeutic drug monitoring of thiopurine drugs in patients with inflammatory bowel disease or autoimmune hepatitis

European Journal of Gastroenterology & Hepatology ◽

10.1097/00042737-200412000-00028 ◽

2004 ◽

Vol 16 (12) ◽

pp. 1407-1413 ◽

Cited By ~ 25

Author(s):

Barbara Wusk ◽

Gerd A Kullak-Ublick ◽

Christina Rammert ◽

Arnold von Eckardstein ◽

Michael Fried ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Therapeutic Drug Monitoring ◽

Autoimmune Hepatitis ◽

Bowel Disease ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Inflammatory Bowel

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Therapeutic drug monitoring with vedolizumab in inflammatory bowel disease

Minerva Gastroenterologica e Dietologica ◽

10.23736/s1121-421x.19.02625-4 ◽

2020 ◽

Vol 65 (4) ◽

Author(s):

Daniela Pugliese ◽

Giuseppe Privitera ◽

Fabrizio Pizzolante ◽

Antonio Gasbarrini ◽

Luisa Guidi ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Therapeutic Drug Monitoring ◽

Bowel Disease ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Inflammatory Bowel

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Faculty Opinions recommendation of Therapeutic Drug Monitoring During Induction of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: Defining a Therapeutic Drug Window.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.728770716.793568133 ◽

2019 ◽

Author(s):

Ashish Patel

Keyword(s):

Inflammatory Bowel Disease ◽

Tumor Necrosis Factor ◽

Therapeutic Drug Monitoring ◽

Bowel Disease ◽

Drug Monitoring ◽

Tumor Necrosis ◽

Therapeutic Drug ◽

Factor Therapy ◽

Inflammatory Bowel ◽

Necrosis Factor

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Anti Tumor Necrosis Factor-a Monoclonal Antibody (Infliximab) Therapy in Patients with Inflammatory Bowel Disease (IBD): Applications and Side Effects

Drug Design Reviews - Online ◽

10.2174/1567269043480645 ◽

2004 ◽

Vol 1 (2) ◽

pp. 111-117 ◽

Cited By ~ 1

Author(s):

L. Amati ◽

M. Passeri ◽

M. Mastronardi ◽

E. Jirillo

Keyword(s):

Inflammatory Bowel Disease ◽

Monoclonal Antibody ◽

Side Effects ◽

Tumor Necrosis Factor ◽

Bowel Disease ◽

Tumor Necrosis ◽

Infliximab Therapy ◽

Inflammatory Bowel ◽

Necrosis Factor

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A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.154 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 162-163

Author(s):

M Mikail ◽

A Wilson

Keyword(s):

Inflammatory Bowel Disease ◽

Pyoderma Gangrenosum ◽

Bowel Disease ◽

Complete Resolution ◽

Therapeutic Drug ◽

Drug Concentrations ◽

Median Serum ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

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SAT0462 ASSESSMENT OF BONE MINERAL DENSITY IN INFLAMMATORY BOWEL DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6007 ◽

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

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Su1984 CLINICAL PRESENTATION AND OUTCOMES OF PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS IN INFLAMMATORY BOWEL DISEASE

Gastroenterology ◽

10.1016/s0016-5085(20)32510-5 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-732-S-733

Author(s):

Camilla A. Martins ◽

Ana Elisa R. Caon ◽

Marilia G. Cruz ◽

Luísa L. Barros ◽

Alexandre Carlos ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Autoimmune Hepatitis ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Clinical Presentation ◽

Inflammatory Bowel

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Impact of COVID-19 on the diagnosis, assessment and management of children with inflammatory bowel disease in the UK: implications for practice

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000786 ◽

2020 ◽

Vol 4 (1) ◽

pp. e000786

Author(s):

Abbie Maclean ◽

James J Ashton ◽

Vikki Garrick ◽

R Mark Beattie ◽

Richard Hansen

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Delayed Diagnosis ◽

High Standard ◽

Current Evidence ◽

Faecal Calprotectin ◽

Paediatric Patients ◽

Inflammatory Bowel ◽

Working Practices ◽

The Impact

The assessment and management of patients with known, or suspected, paediatric inflammatory bowel disease (PIBD) has been hugely impacted by the COVID-19 pandemic. Although current evidence of the impact of COVID-19 infection in children with PIBD has provided a degree of reassurance, there continues to be the potential for significant secondary harm caused by the changes to normal working practices and reorganisation of services.Disruption to the normal running of diagnostic and assessment procedures, such as endoscopy, has resulted in the potential for secondary harm to patients including delayed diagnosis and delay in treatment. Difficult management decisions have been made in order to minimise COVID-19 risk for this patient group while avoiding harm. Initiating and continuing immunosuppressive and biological therapies in the absence of normal surveillance and diagnostic procedures have posed many challenges.Despite this, changes to working practices, including virtual clinic appointments, home faecal calprotectin testing kits and continued intensive support from clinical nurse specialists and other members of the multidisciplinary team, have resulted in patients still receiving a high standard of care, with those who require face-to-face intervention being highlighted.These changes have the potential to revolutionise the way in which patients receive routine care in the future, with the inclusion of telemedicine increasingly attractive for stable patients. There is also the need to use lessons learnt from this pandemic to plan for a possible second wave, or future pandemics as well as implementing some permanent changes to normal working practices.In this review, we describe the diagnosis, management and direct impact of COVID-19 in paediatric patients with IBD. We summarise the guidance and describe the implemented changes, evolving evidence and the implications of this virus on paediatric patients with IBD and working practices.

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