A5037336413- Acute Lymphoblastic Leukemia research
- Inflammatory Bowel Disease
- Microscopic Colitis
- Adolescent and Pediatric Healthcare
- Liver Diseases and Immunity
- Pregnancy and Medication Impact
- Celiac Disease Research and Management
- Childhood Cancer Survivors' Quality of Life
- Chronic Lymphocytic Leukemia Research
- Folate and B Vitamins Research
- Autoimmune and Inflammatory Disorders Research
- Pancreatitis Pathology and Treatment
- Biochemical and Molecular Research
- Helicobacter pylori-related gastroenterology studies
- Chronic Myeloid Leukemia Treatments
- Primary Care and Health Outcomes
- Renal Transplantation Outcomes and Treatments
- Immunodeficiency and Autoimmune Disorders
- Clinical Nutrition and Gastroenterology
- Eosinophilic Esophagitis
- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Prenatal Screening and Diagnostics
- Chronic Disease Management Strategies
- Biosimilars and Bioanalytical Methods
Rajiv Gandhi Cancer Institute and Research Centre
2024-2025
University of North Sumatra
2024
London Bridge Hospital
2024
Varian Medical Systems (Germany)
2024
King George Hospital
2023
East Surrey Hospital
2010-2021
Surrey and Sussex Healthcare NHS Trust
2014-2021
Royal Surrey NHS Foundation Trust
2021
Post Graduate Institute of Medical Education and Research
2021
University of Amsterdam
2020
Adverse drug reactions to azathioprine (AZA), the pro-drug of 6-mercaptopurine (6-MP), occur in 15% 28% patients and majority are not explained by thiopurine methyltransferase (TPMT) deficiency. Inosine triphosphate pyrophosphatase (ITPase) deficiency results benign accumulation inosine nucleotide ITP. 6-MP is activated through a 6-thio-IMP intermediate and, ITPase deficient patients, potentially toxic 6-thio-ITP predicted accumulate. The association between polymorphism ITPA gene adverse...
Summary Background : Azathioprine therapy is discontinued in one‐third of patients with inflammatory bowel disease because toxicity or a lack clinical response. Patients thiopurine methyltransferase (TPMT) deficiency are intolerant to azathioprine, whilst carriers at increased risk side‐effects. Aim To evaluate the importance TPMT activity management azathioprine disease. Methods Clinical response, adverse effects and haematological parameters were determined correlated enzyme genotype 106...
To investigate whether pharmacogenetic loci or metabolite concentrations explain clinical response side effects to AZA.Patients with IBD were given 2 mg/kg of AZA without dose escalation adjustment. Serial response, thiopurine methyl transferase (TPMT) activity and thioguanine nucleotide (TGN) measured over 6 months. All patients genotyped for inosine triphosphatase (ITPase) TPMT. Clinical compared these variables.Two hundred seven analysed. Thirty-nine per cent withdrew due adverse effects....
Aliment Pharmacol Ther 31 , 640–647 Summary Background The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently. Aim To study combination of allopurinol with reduced‐dose in an attempt to avoid the treatment Methods Patients full‐dose thiopurines were recruited therapy two IBD centres this retrospective study. Dosing was guided measuring methyltransferase (for UK patients)...
Hepatotoxicity results in the withdrawal of thiopurines drugs, azathioprine (AZA) and mercaptopurine (MP), up to 10% patients with inflammatory bowel disease. Our group previously demonstrated that allopurinol AZA/ciclosporin/steroid 'triple therapy' improved renal graft survival.To confirm hypothesis may alleviate thiopurine hepatotoxicity by similar mechanisms as proposed our study.Unselected acute were offered co-therapy low-dose AZA or MP. The starting AZA/MP dose was determined...
Summary Background Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) aldehyde oxidase (AO) compete with inactivate AZA. Aim To assess whether genetic AOX1 , XDH MOCOS (the product of which activates the essential cofactor for AO XDH) associated AZA outcome IBD. Methods Real‐time PCR was conducted a panel single nucleotide (SNPs) AOX1, using TaqMan SNP genotyping assays...
Inosine triphosphate pyrophosphatase (ITPase) deficiency occurs with polymorphic frequencies in Caucasians and results the benign accumulation of inosine nucleotide ITP. In 62 patients treated azathioprine for inflammatory bowel disease, ITPA 94C>A deficiency-associated allele was significantly associated adverse drug reactions (OR 4.2, 95% CI 1.6-11.5, p = 0.0034). Significant associations were found flu-like symptoms 4.7, 1.2-18.1, 0.0308), rash 10.3, 4.7-62.9, 0.0213) pancreatitis 6.2,...
Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) the benefit of overcoming side effects regularly associated thiopurine monotherapy and poor responses. Concerns regarding safety remain, while layer complexity added by trend toward treatment directed red cell thioguanine nucleotide (TGN) profiling. We report on clinical efficacy LDAA use IBD undirected metabolite profiling.Observational study practice from single center....
Thioguanine (TG) is a treatment for inflammatory bowel disease, but association with nodular regenerative hyperplasia has restricted its use. We conjectured that splitting therapeutic daily dose of TG would be efficacious and should avoid liver toxicity.We report on 62 patients severe disease not responding to prednisolone, conventional thiopurines, biologics, or calcineurin inhibitors. Patients were prescribed oral split-daily individual doses >0.3 mg/kg. Data concomitant medication,...
Thiopurine drugs (azathioprine and 6-mercaptopurine) are well established in the treatment of patients with inflammatory bowel disease. However, some intolerant or resistant to thiopurine their management remains a challenge. Several studies have suggested methotrexate is effective for induction maintenance remission Crohn's disease.This study was conducted because overall data on clinical efficacy disease remain limited there no regarding fistulating concomitant use retrospective review...
Objective Polymorphisms in the TPMT gene open reading frame (ORF) are associated with reduced activity. Variable number tandem repeats (VNTR*3 to VNTR*9) promoter region of consisting combinations Type A, B and C repeat units, may modulate Here we present allele frequencies genetic modifiers activity a British Asian population, as well concordance between intermediate ORF VNTR genotypes predominantly Caucasian population. Methods type mutations were determined two selected ranges, (4–8 U,...
The immunosuppressive drug 6-mercaptopurine (6-MP) and its prodrug azathioprine are used in the treatment of inflammatory bowel disease other disorders immune regulation (1). Thiopurine methyltransferase (TPMT) inactivates 6-MP by methylation. genetic variants TPMT *2 to *19 associated with decreased activity (2), TPMT*3A , * 3C most common deficiency-associated A heterozygous genotype (1 10 individuals from general population) is an increased risk myelosuppression standard-dose therapy (3)...
6-Thioguanine (6-TG) is efficacious in patients with Crohn's Disease (CD) failing conventional immunosuppression but there are reports of hepatotoxicity. We report our experience the safety and efficacy 6-TG a series CD.A retrospective study CD who failed thiopurines +/- methotrexate between 2001 2006 was performed. Indications for were; active disease, to allow infliximab withdrawal, steroid sparing, or fistula closure. Patients underwent regular review those treated longer than 1 year were...
Background: Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn’s (CD), relapse is frequent, and there little information regarding long-term outcomes terms of response to subsequent treatments complications ASCT. Design: Retrospective evaluation UK patients treated on a compassionate basis from three tertiary centres. Methods: We summarize six previously unreported with CD ASCT according international guidelines between 2003...
Abstract Background Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events suboptimal response. Its widespread use hampered concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim this study was investigate long-term efficacy and safety low-dose TG therapy in IBD failing AZA MP. Methods A retrospective multicentre performed prior treatment...
Beneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due high rates of adverse events. Co-administrating allopurinol has been shown improve tolerability. However, data on this co-therapy as treatment are scarce.Retrospective comparison long-term effectiveness and safety low-dose azathioprine-allopurinol (LDAA) monotherapy (AZAm) IBD without metabolite monitoring.Clinical benefit was defined ongoing therapy initiation...
Summary Background The thiopurines, azathioprine (AZA) and mercaptopurine are extensively used in Crohn’s disease (CD). Thiopurine bioactivation can be diverted by either thiopurine methyltransferase (TPMT), or xanthine oxidase/dehydrogenase (XOD) which forms 6‐thiouric acid (6TU). Aim To investigate whether chronic inflammation could influence small intestinal XOD activity using urinary excretion of 6TU as a surrogate marker activity. Methods 6‐Thiouric was compared between 32 CD patients...