Perinatal risk factors and coeliac disease in children and young adults: a record linkage study

Background  Little is known about perinatal risk factors and coeliac disease.
Aim  To investigate the relationship between perinatal risk factors and subsequent coeliac disease among offspring.
Methods  Record linked abstracts of birth registrations, maternity, in-patient and day case records in a defined population of southern England.
Results  Using univariate analysis, coeliac disease in the child was associated with maternal coeliac disease (odds ratio = 20.6; 95% CI = 5.04–84.0; based on two cases in both mother and child) and with social class, year of birth, maternal smoking and parity. Multivariate analysis confirmed an increased risk of coeliac disease of 3.79 (95% CI = 1.85–7.79) for classes IV and V compared with I and II, an increased risk of 1.92 (1.06–3.49) for births during 1975–1979 compared with 1970–1974 and an increased risk of 1.80 (1.05–3.09) for 'subsequent' compared with 'first' births. Smoking during pregnancy was no longer associated with coeliac disease. Because numbers were small, maternal coeliac disease was excluded from the multivariate anaylsis.
Conclusions  This study shows increased risks of coeliac disease for manual social classes, births during the late 1970s and 'subsequent' births. Overall, perinatal risk factors seem to have a limited role in the aetiology of coeliac disease in children and young adults.     

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.
Aims  To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population.
Methods  Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios.
Results  Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77–1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73–1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67–3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44–6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03–1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70–1.23).
Conclusions  Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.     

Coeliac disease and the risk of fractures - a general population-based cohort study

BACKGROUND: Earlier studies have suggested that untreated coeliac disease may be associated with osteoporosis, but results are contradictory for the risk of long-term fractures. AIM: To study the association between coeliac disease and fractures. METHODS: We used Cox regresson to examine the future risk of hip fracture and fracture of any type in more than 13 000 individuals with coeliac disease and 65 000 age- and sex-matched reference individuals in a general population-based cohort. RESULTS: During follow-up, 1365 first hip fractures and 4847 fractures of any type occurred. Coeliac disease was positively associated with subsequent hip fracture (hazard ratio = 2.1; 95% CI = 1.8-2.4) (in children: hazard ratio = 2.6; 95% CI = 1.1-6.2) and fractures of any type (hazard ratio = 1.4; 95% CI = 1.3-1.5) (in children: hazard ratio = 1.1; 95% CI = 1.0-1.2). The absolute excess risk of hip fractures in children with coeliac disease was 4/100 000 person-years. Incidence ratios for hip fracture in individuals with CD were around two both prior to diagnosis of coeliac disease and afterwards; this risk increase remained 20 years after diagnosis of coeliac disease. CONCLUSIONS: Individuals with coeliac disease, including children with coeliac disease, may be at increased risk of hip fracture and fracture of any type. Coeliac disease may be positively associated with long-term hip fracture risk.     

No difference in mortality in undetected coeliac disease compared with the general population: a UK cohort study

Aliment Pharmacol Ther 2011; 34: 1012–1019

Summary

Background Studies of mortality in undetected coeliac disease compared with the general population give contradictory findings, suggesting it is either increased fourfold compared with the general population or not at all. Aim To establish all‐cause and cause‐specific mortality in undiagnosed coeliac disease, identified by anti‐endomysial antibody (EMA) positivity, in the Cambridge GP Health Survey cohort. Method This cohort was recruited in 1990 from the general population aged 45–76 years. All deaths were ascertained from the Office for National Statistics. Mortality rates were calculated per 1000 person years and adjusted for age, gender, smoking and socioeconomic group using multivariate Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results There were 117 914 patient years of follow‐up (median 16.8 years) from 7527 participants. Eighty‐seven had undetected coeliac disease, their all‐cause mortality rate was 9.4 per 1000 person years (95% CI 5.4–16.1) compared with 12.7 (95% CI 12.1–13.4) in EMA‐negative participants. The adjusted all‐cause mortality HR was 0.98 (95% CI 0.57–1.69). Death due to cancer and circulatory diseases was not increased, adjusted HR were 1.27 (95% CI 0.57–2.85) and 1.39 (95% CI 0.66–2.92) respectively. Conclusions We observed no excess overall mortality in people aged over 45 years with undetected coeliac disease compared with the general population, nor any increase in deaths related to circulatory disease or cancer. Our findings do not support screening the general population aged over 45 years, for coeliac disease for the purpose of improving life expectancy.     

Epidemiological study of gastro-oesophageal reflux disease: reflux in spouse as a risk factor

Background  Gastro-oesophageal reflux disease (GERD) is a growing health-care problem with variable distribution.
Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population-based study.
Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self-administered questionnaires were used.
Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m² (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first-degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first-degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months ( P  < 0.05).
Conclusions  Gastro-oesophageal reflux disease is common in Tehran. The association of 'infrequent symptoms' with GERD history in first-degree relatives and 'frequent symptoms' with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.     

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis

Background  Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis.
Aim  To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease.
Methods  Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n  = 5073).
Results  A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n  = 46, mesalazine (mesalamine) n  = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P  = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6–20.6; P  = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n  = 1477) (OR 5.2 95% CI: 1.8–14; P  = 0.002).
Conclusions  The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.     

Proton pump inhibitors increase significantly the risk of Clostridium difficile infection in a low-endemicity, non-outbreak hospital setting

Background  Proton pump inhibitors (PPI) have been linked to higher risk of Clostridium difficile infection (CDI). The relevance of this association in hospitals with low disease activity, where an outbreak strain is nondominant, has been assessed in relatively few studies.
Aim  To assess the association of PPI and CDI in a setting of low disease activity.
Methods  A retrospective cohort study was conducted at two hospitals. Patients admitted for ≥7 days receiving antibiotics were included. Demographics, exposure to PPI, antibiotics and other drugs in relation to diagnosis of CDI were assessed by univariate and multivariate analyses.
Results  Of 14 719 patients, 149 (1%) first episode CDI were documented; PPI co-exposure increased CDI [1.44 cases/100 patients vs. 0.74 cases/100 non-exposed (OR: 1.96, 95% CI: 1.42–2.72)]. By logistic regression, PPI days (adjusted OR: 1.01 per day, 95% CI: 1.00–1.02), histamine-2 blockers, antidepressants, antibiotic days, exposure to medications, age, admission service and length of admission were significant predictors.
Conclusions  A statistically significant increase in CDI was observed in antibiotic recipients who received PPI, but the absolute risk increase is modest. In settings of with low rates of CDI, the benefit of PPI therapy outweighs the risk of developing CDI. These data support programmes to decrease inappropriate use of PPI in hospitalized patients.     

Screening differences and risk of cervical cancer in inflammatory bowel disease

Background  Cervical cancer risk is high among immune suppressed women.
Aim  To evaluate inflammatory bowel disease (IBD) with medications and risk of cervical cancer.
Methods  Members of Kaiser Permanente Northern California (KPNC), 15–68 years from 1996 to 2006 with IBD were compared with age-matched women without IBD. Cervical cancer was ascertained using the KPNC Cancer Registry. IBD medications of interest were aminosalicylates (ASA), corticosteroids, immune modulators and infliximab. Odds of cervical cancer were analysed with adjusted logistic regression. The prevalence of Pap smear testing was compared using a log binomial model.
Results  Ten cervical cancer cases occurred among 1165 women with IBD and 72 cancers among 12 124 controls. The adjusted odds ratio (OR) of IBD with risk of cervical cancer was 1.45 [95% confidence interval (CI) 0.74–2.84]. Medication ORs were 1.65 for ASA, 2.79 for corticosteroids and 3.45 for immune modulators (all P  > 0.05). No cancer case used infliximab. The adjusted absolute increase in Pap smears among IBD women compared to women without IBD was 4% (95% CI 2–5%).
Conclusions  Although a trend of elevated risk for cervical cancer with IBD and IBD medications was observed, it was not statistically significant. Regular cervical cancer screening for women with IBD is recommended.     

Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease

Background  Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity.
Aim  To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies.
Methods  Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease.
Results  Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6–89.9) and 93.0% (95% CI, 91.2–94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5–95.5) and 96.5% (95% CI, 95.2–97.5) respectively.
Conclusion  Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease.     

Anti-tissue transglutaminase antibodies in the follow-up of adult coeliac disease

Background  The detection of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies) has a well-established role in the diagnosis of coeliac disease, but the value of these antibodies in long-term follow-up is controversial.
Aims  To determine if serial anti-tTG antibody measurements could confirm adherence to a gluten-free diet (GFD) and identify patients at risk of disease complications.
Methods  In a 54-month cohort follow-up study, 182 adult patients were assessed. Data recorded included self-assessment of GFD adherence; anti-tTG antibody concentration and serum ferritin, vitamin B12 and folate. Where available, bone mineral density (BMD) and duodenal histology data were retrieved.
Results  Persistently elevated anti-tTG antibody levels were significantly associated with abnormal duodenal histology ( P  < 0.001), low ferritin ( P  < 0.01) and poor adherence to the GFD ( P  < 0.001). The specificity was >85% while the sensitivity was 39–60%. Anti-tTG antibody concentrations fell rapidly following successful initiation of a GFD, and maintenance of normalization identified those who continued to be adherent to the diet.
Conclusions  This study supports a strategy of using anti-tTG antibody concentrations to monitor newly diagnosed and established patients with coeliac disease, and to target dietetic intervention to reduce the risk of complication.     

Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

Predictors of serious complications due to Clostridium difficile infection

Background  Identifying individuals with severe Clostridium difficile infection (CDI) at risk for major complications has become an important objective. Presence of clinical variables that predict complications from CDI would have the potential to strongly influence management.
Aim  To determine which clinical variables predict complications from CDI.
Methods  Cross-sectional study of all individuals admitted to Temple University Hospital between 12/1/03 and 7/1/08 with the primary discharge diagnosis of CDI were eligible. Only patients experiencing their first episode of CDI were included. Abstracted data included demographic, physiological, laboratory, radiological, endoscopic, pharmacy and outcome data. Response was categorized as none, partial or complete. Complications attributed to CDI were defined as colon resection or death.
Results  Overall 32 of 200 patients (16%) experienced a complication due to CDI including death ( n  = 20) and colectomy ( n  = 12). White blood cell count above 30,000 cells/mm³ (OR = 4.06; 95% CI, 1.28–12.87) and a rise in the creatinine to over 50% above baseline (OR = 7.13; 95% CI, 3.05–16.68) predicted a complication. AROC for percent rise in serum creatinine was 0.73 (95% CI: 0.64–0.85) and 0.62 (95% CI: 0.58–0.80) for white blood cell count.
Conclusions  Severe white blood cell count elevation and a rise in the creatinine to over 50% above baseline are important independent predictors of serious adverse events due to CDI. These patients likely would benefit from more intensive care and early surgical consultation.     

Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis C

Background  Antiviral treatment with interferon-alpha (IFN-α) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors.
Aim  To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-α) on mental health in patients with psychiatric risk factors.
Method  We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery–Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-α and ribavirin.
Results  Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score ≥5 (OR 14.21, 95% CI: 2.51–81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024–0.558), methadone substitution (OR = 0.20, 95% CI: 0.045–0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138–0.845) were significantly less likely to show a long-term worsening of depressive symptoms.
Conclusions  Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-α.     

Systematic review: the epidemiology of gastro-oesophageal reflux disease in primary care, using the UK General Practice Research Database

Background  Gastro-oesophageal reflux disease (GERD) is a common diagnosis in primary care; however, there has been no comprehensive review of the epidemiology of GERD in this setting.
Aim  To review systematically articles that used the General Practice Research Database to study the epidemiology of GERD.
Methods  Systematic literature searches.
Results  Seventeen articles fulfilled the inclusion criteria. The incidence of GERD in primary care was 4.5 new diagnoses per 1000 person-years in 1996 (95% CI: 4.4–4.7). A new diagnosis of GERD was associated with being overweight, obese or an ex-smoker. Prior diagnoses of ischaemic heart disease, peptic ulcer disease, nonspecific chest pain, nonspecific abdominal pain, chronic obstructive pulmonary disease and asthma were associated with a subsequent new GERD diagnosis. A first diagnosis of GERD was associated with an increased risk of a subsequent diagnosis of oesophageal adenocarcinoma, oesophageal stricture, chronic cough, sinusitis, chest pain, angina, gallbladder disease, irritable bowel syndrome or sleep problems. Mortality may be higher in patients with a GERD diagnosis than in those without in the first year after diagnosis, but not long term.
Conclusion  The General Practice Research Database is an effective way of studying the epidemiology of GERD in a large population-based primary care setting.     

Infliximab dependency in children with Crohn's disease

Background  Recently, infliximab dependency has been described.
Aim  To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000–2006 and to describe clinical and genetic predictors of long-term infliximab response.
Methods  A phenotype model of infliximab dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start) – complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse ≤90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF -308 A>G, TNF -857 C>T, Casp9 93 C>T, FasL -844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed.
Results  Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24–22.55; OR 6.7, 95% CI: 1.67–26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders ( P  = 0.0002).
Conclusions  Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype.     

The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up

Background  Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC).
Aim  To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007.
Methods  Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0–4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab.
Results  Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious).
Conclusions  Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy.     

Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study

Background  Between 3% and 40% of patients surviving an episode of upper gastrointestinal bleeding (UGIB) experience a recurrence within 1 year.
Aim  To characterize further the recurrence rate of UGIB and to investigate the role of long-term acid suppressive therapy in its secondary prevention.
Methods  Recurrent cases of UGIB were identified among patients registered in The Health Improvement Network in the UK. A nested case–control analysis provided relative risk (RR) estimates of factors associated with recurrence.
Results  Of 1287 patients included, 67 (5.2%) were identified with a recurrent UGIB episode, corresponding to a recurrence rate of 17.5 per 1000 person-years during a mean follow-up of 3 years. The greatest risk of recurrence was in patients prescribed the oral anticoagulant warfarin (RR: 5.38; 95% confidence interval: 2.02–14.36). Use of a single proton pump inhibitor (PPIs) was associated with a reduced risk of recurrence (RR: 0.51; 95% confidence interval: 0.26–0.99), even in patients taking warfarin, while current use of H₂-receptor antagonists was not. After the first episode of UGIB, use of nonsteroidal anti-inflammatory drugs and aspirin was greatly reduced, preventing estimation of the risk associated with these drugs.
Conclusion  Long-term PPI therapy reduces the risk of UGIB recurrence.     

Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease

Background  Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) and aldehyde oxidase (AO) compete with TPMT to inactivate AZA.
Aim  To assess whether genetic polymorphism in AOX1 , XDH and MOCOS (the product of which activates the essential cofactor for AO and XDH) is associated with AZA treatment outcome in IBD.
Methods  Real-time PCR was conducted for a panel of single nucleotide polymorphism (SNPs) in AOX1, XDH and MOCOS using TaqMan SNP genotyping assays in a prospective cohort of 192 patients receiving AZA for IBD.
Results  Single nucleotide polymorphism AOX1 c.3404A > G (Asn1135Ser, rs55754655) predicted lack of AZA response ( P  = 0.035, OR 2.54, 95%CI 1.06–6.13) and when combined with TPMT activity, this information allowed stratification of a patient's chance of AZA response, ranging from 86% in patients where both markers were favourable to 33% where they were unfavourable ( P  < 0.0001). We also demonstrated a weak protective effect against adverse drug reactions (ADRs) from SNPs XDH c.837C > T ( P  = 0.048, OR 0.23, 95% CI 0.05–1.05) and MOCOS c.2107A > C, ( P  = 0.058 in recessive model, OR 0.64, 95%CI 0.36–1.15), which was stronger where they coincided ( P  = 0.019).
Conclusion  These findings have important implications for clinical practice and our understanding of AZA metabolism.