We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease

Genome-wide association studies (GWAS) and candidate gene studies in ulcerative colitis (UC) have identified 18 susceptibility loci. We conducted a meta-analysis of 6 UC GWAS, comprising 6,687 cases and 19,718 controls, and followed-up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P<5×10-8), increasing the number of UC associated loci to 47. After annotating associated regions using GRAIL, eQTL data and correlations with non-synonymous SNPs, we identified many candidate genes providing potentially important insights into disease pathogenesis, including IL1R2, IL8RA/B, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease (IBD) risk loci is now 99, including a minimum of 28 shared association signals between Crohn’s disease (CD) and UC.

Proton pump inhibitors have dramatically influenced the management of acid‐peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors. Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors. Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.

Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

IBD is at least as common in Canterbury as in other western regions. CD incidence and prevalence are amongst the highest ever reported and are higher than for UC. IBD population characteristics are otherwise similar to other countries. The Canterbury IBD Project will be a valuable tool for future population-based IBD epidemiology and genetics research.

1. Once‐daily aminoglycoside dosing has many advantages and has been widely advocated. However, existing guidelines for methods of administration and monitoring are non‐specific and may lead to excessive dosing. 2. The traditional approach of aiming for target peak and trough concentrations is not appropriate for once‐daily dosing. 3. A method is proposed which uses a target area under the concentration‐ time curve (AUC) for the aminoglycoside based on the 24 h AUC that would result with conventional dosing. This method requires measurement of two drug concentrations, one approximately 0.5 h after the end of the infusion and another at a later time (6‐22 h) depending on renal function. 4. A simpler, graphical method is also proposed for patients with normal renal function, which requires the measurement of a single concentration at a time between 6 and 14 h. 5. Both methods are likely to be safer than existing guidelines.

The thiopurine drugs azathioprine and 6-mercaptopurine (6-MP) are well-established in the treatment of inflammatory bowel disease (IBD). However, there is a wide inter- and intra-patient variation in the concentrations of active and toxic metabolites due to their complex metabolism and genetic polymorphisms in metabolizing enzymes. Serious drug toxicity leads to cessation of therapy in 9-25% of patients, and there is failure to achieve efficacy in approximately 15% of cases. Advances in the understanding of thiopurine drug metabolism have led to new genetic and metabolite tests to help clinicians optimize thiopurine use. Thiopurine methyltransferase (TPMT) enzyme activity can predict life-threatening myelotoxicity in the one in 300 patients who are TPMT-deficient. However, myelotoxicity can also occur in the presence of normal TPMT activity so blood count monitoring should remain standard practice. TPMT testing may also aid in dose individualization. 6-Thioguanine nucleotides (6-TGN) are thought to be the predominant active metabolites of the thiopurines. 6-thioguanine nucleotide concentration is correlated with bone marrow toxicity and may also correlate with efficacy in IBD. Measurement of 6-TGN and 6-methylmercaptopurine (6-MMP) concentration is most useful in determining why a patient is not responding to a standard dose of a thiopurine drug and may help in avoiding myelosuppression. The ratio of these metabolites can help distinguish non-compliance, under-dosing, thiopurine-resistant and thiopurine-refractory disease. Some of these investigations are entering routine clinical practice but more research is required to determine their optimal use in patients with IBD.

Although CD location remains relatively stable, behavior changes over time. Perianal disease is a strong predictor of developing more complicated CD. Proctitis is most common in UC patients at diagnosis although younger patients are more likely than older patients to have extensive disease. The Montreal classification provides a clinically useful framework for both researchers and clinicians.