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Background: Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research., Methods: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement., Results: Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record-integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration., Conclusions: Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory., Competing Interests: Z. Wang is supported by a doctoral research grant from the Research Foundation—Flanders (FWO), Belgium (grant number: 1SF2922N). M. Barclay received consultancy fees from Douglas Pharmaceuticals and Janssen unrelated to submitted work. T. Mizuno served as a consultant of NDA Partners and received speaker honoraria from Astellas Pharma Inc. and Chugai Pharmaceutical Co. R. J. Keizer is an employee and stockholder of InsightRX, a company developing precision dosing software. S. G. Wicha received research grants from Boehringer Ingelheim and AqVida, consulting fees from Merck KGaA and Medicines from Malaria Venture, and speaker honoraria from GlaxoSmithKline. J. Lambert received unrestricted grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB, served as a speaker for AbbVie, Almirall, Bristol-Myers Squibb, Janssen-Cilag, Pfizer, and UCB, and served as a consultant for AbbVie, argenx, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB, with all fees and grants being paid to Ghent University (Hospital) scientific accounts and not to any personal account of Jo Lambert. S. Vermeire received grants from AbbVie, J&J, Pfizer, Galapagos, and Takeda, received consulting and/or speaker fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MRM Health, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, and Zealand Pharma. K. Papamichael received lecture/speaker fees from Physicians Education Resource LLC and Grifols, scientific advisory board fees from ProciseDx Inc. and Scipher Medicine Corporation, and serves as a consultant from Prometheus Laboratories Inc. E. Dreesen received consultancy fees from Alimentiv, argenx, and Prometheus, lecture fees from Galapagos, and financial support from Janssen and Sandoz, outside the submitted work, with all honoraria/fees being paid to KU Leuven and not to any personal account of Erwin Dreesen. D. Alsoud, D. J. A. R. Moes, R. Soenen, Z. Layegh, I. K. Minichmayr, G. Wolbink, A. de Vries, and N. Padullés-Zamora declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined., Aims: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes., Methods: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved., Results: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 10 8 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 10 8 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 10 8 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved., Conclusions: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear., (© 2021 John Wiley & Sons Ltd.)

Background: Providing timely follow-up care for patients with inflammatory bowel disease in remission is important but often difficult because of resource limitations. Using smartphones to communicate symptoms and biomarkers is a potential alternative. We aimed to compare outpatient management using 2 smartphone apps (IBDsmart for symptoms and IBDoc for fecal calprotectin monitoring) vs standard face-to-face care. We hypothesized noninferiority of quality of life and symptoms at 12 months plus a reduction in face-to-face appointments in the smartphone app group., Methods: Inflammatory bowel disease outpatients (previously seen more often than annually) were randomized to smartphone app or standard face-to-face care over 12 months. Quality of life and symptoms were measured quarterly for 12 months. Acceptability was measured for gastroenterologists and patients at 12 months., Results: One hundred people (73 Crohn's disease, 49 male, average age 35 years) consented and completed baseline questionnaires (50 in each group). Intention-to-treat and per-protocol analyses revealed noninferiority of quality of life and symptom scores at 12 months. Outpatient appointment numbers were reduced in smartphone app care (P < 0.001). There was no difference in number of surgical outpatient appointments or number of disease-related hospitalizations between groups. Adherence to IBDsmart (50% perfect adherence) was slightly better than adherence to IBDoc (30% perfect adherence). Good acceptability was reported among most gastroenterologists and patients., Conclusions: Remote symptom and fecal calprotectin monitoring is effective and acceptable. It also reduces the need for face-to-face outpatient appointments. Patients with mild-to-moderate disease who are not new diagnoses are ideal for this system., Clinical Trial Registration Number: ACTRN12615000342516., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Thiopurine hypermethylation towards 6-methylmercaptopurine (6MMP) instead of 6-thioguanine nucleotides (6TGN) is associated with inefficacy in patients with IBD. Allopurinol reverses such hypermethylation., Aims: To prospectively determine efficacy of allopurinol-thiopurine combination and to compare 2 doses of allopurinol., Design: In a multicentre, double-blind trial, patients with clinically active or steroid-dependent IBD and thiopurine shunting were randomised to 50 or 100 mg/d allopurinol and 25% of their screening thiopurine dose, which was subsequently optimised, aiming for 6TGN of 260-500 pmol/8x10 8 RBCs. The primary endpoint was steroid-free clinical remission at 24 weeks., Results: Of 73 patients, 39 (53% [95% CI 42-65]) achieved steroid-free remission, (54% with 50 mg/d and 53% with 100 mg/d). 81% were able to discontinue steroids. Therapeutic 6TGN levels were achieved in both groups. Final thiopurine doses were lower with 100 mg/d allopurinol (P < 0.005). 6MMP: 6TGN ratio decreased from mean 64 to 4 (P < 0.001), being higher with 50 mg/d (6 ± 1.83) than for 100 mg/d ([1 ± 0.16], P = 0.003). Three patients on 50 mg/d failed to sustain low ratios at 24 weeks. Toxicity was minimal; three patients on 50 mg/d allopurinol developed transient leukopenia. Alanine aminotransferase concentrations decreased (P < 0.001) similarly in both arms. Faecal calprotectin levels at study end were lower in patients who achieved the primary endpoint (median 171 [85-541] vs 821[110-5892] ug/g, P = 0.03)., Conclusions: Low-dose allopurinol-thiopurine combination safely reverses shunting and optimises 6TGN with associated improvement in disease activity. 100 mg/d allopurinol is preferable due to greater metabolite profile stability and lower thiopurine dose without additional toxicity., (© 2018 John Wiley & Sons Ltd.)

Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last 2 decades. Combination therapy was not superior in any of the registration trials for Crohn's disease and ulcerative colitis for TNF antagonists, vedolizumab, or ustekinumab. It needs to be mentioned, though, that none of these trials were powered to detect such differences, and that many patients entered the trial after having failed conventional immunosuppressives.Postmarketing studies revealed that patients on background immunosuppression have a lower risk of immunogenicity (often resulting in infusion/injection reactions) than patients on monotherapy. In the SONIC and UC-SUCCESS trials, superiority of the combination azathioprine-infliximab was demonstrated in Crohn's disease and ulcerative colitis, respectively. This trial design has not been used with any other biologic for IBD, so far. Meanwhile, it has also become clear that combination treatment with TNF antagonists is associated with increased toxicity, mainly infections, but also malignancy such as lymphoproliferative disease. This toxicity could perhaps be reduced by using lower doses of immunosuppressives, a strategy that has been shown to be equally potent in reducing immunogenicity. Additionally, combination treatment could be used for a limited period of time (12 months or even shorter) since most immunogenicity develops in the beginning of the biologic treatment. Patients who develop anti-drug-antibodies later on can often be rescued by reintroduction of thiopurines or methotrexate.In summary, combination treatment is certainly beneficial with infliximab, at least in the first 12 months of treatment. With other TNF antagonists, vedolizumab, and ustekinumab, the available data do not offer clear guidance. In patients without increased risk of toxicity, and certainly in those with limited treatment options, it may be wise to offer combination treatment with all biologics for the time being and at least during the initiation phase.

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., (© 2017 John Wiley & Sons Ltd.)

Background: Up to 20% of patients on thiopurine therapy fail to achieve adequate drug response. Many of these patients preferentially produce the toxic 6-methylmercaptopurine metabolites (6-MMP) rather than the active 6-thioguanine nucleotides (6-TGN) resulting in a high 6-MMP/6-TGN ratio (>20) and increased risk of hepatotoxicity., Aim: To determine the prevalence of preferential 6-MMP producers and define the relationships between 6-TGN, 6-MMP and thiopurine methyltransferase (TPMT)., Methods: The database of 6-TGN, 6-MMP and TPMT measurements from patients throughout New Zealand was used to calculate patients' 6-MMP/6-TGN ratios and identify those with high (>20) or normal ratio (≤20).The TPMT enzyme activity was compared amongst the groups., Results: Of 1879 patients with TPMT, 6-TGN and 6-MMP results, 349 (19%) had a 6-MMP/6-TGN ratio >20. The mean TPMT enzyme activity was slightly lower for those with a 6-MMP/6-TGN ratio ≤20 vs. >20, which achieved statistical significance (12.2 vs. 13.2; P < 0.001). However, the distributions of TPMT enzyme activity were similar, with 97% of TPMT results falling between 5.0 and 17.6 IU/mL for both groups. In all, 17% of those with 6-MMP/6-TGN ratio ≤20 were intermediate TPMT metabolisers (TPMT 5.0-9.2 IU/mL) vs. 7% in those with a ratio >20., Conclusions: In this patient population with measured 6-MMP/6-TGN ratios, 19% of patients were preferential 6-MMP producers. The results show that high TPMT enzyme activity is not the major reason for preferential 6-MMP production in most patients with a high metabolite ratio. This suggests that there are one or more important alternative mechanisms for preferentially producing 6-MMP., (© 2012 Blackwell Publishing Ltd.)

The transcription factor glioma-associated oncogene homolog 1 (GLI1) has a central function in gastrointestinal tract development and homeostasis. A non-synonymous single-nucleotide polymorphism (SNP) (rs2228226; Q1100E) in GLI1, which impairs GLI1 function in vitro, has been proposed as a risk factor for inflammatory bowel disease (IBD). In this study, we assessed the cumulative evidence for association of GLI1 with IBD. New genotype data for rs2228226 from New Zealand (907 controls, 990 IBD patients) and Belgian Caucasian case-control data sets (312 controls, 1214 IBD patients) were combined with data from the National Institute of Diabetes and Digestive and Kidney Diseases and three previously studied Caucasian case-control data sets. Meta-analysis of rs2228226 did not detect any association with ulcerative colitis (UC) (P=0.09, odds ratio (OR)=1.07, 95% confidence interval (CI)=0.92-1.24), Crohn's disease (CD) (P=0.29, OR=1.06, 95% CI=0.93-1.21) or overall IBD (P=0.15, OR=1.05, 95% CI=0.92-1.19). Our analyses of rs2228226 suggest that GLI1 is not a significant risk factor for IBD in Caucasians.

Background: Single nucleotide polymorphisms (SNPs) in the multidrug transporter MDR1 have been associated with inflammatory bowel disease (IBD) in different studies. However, the data are highly controversial. Recently, 6 haplotype tagging SNPs (tSNPs), representing the haplotype variations of the MDR1 gene, were identified. The aims of this study were to genotype these variants and correlate them to disease phenotype in New Zealand IBD patients., Materials and Methods: A total of 784 IBD patients and 200 healthy subjects were genotyped for 5 tSNPs and the triallelic MDR1 variant G2677T/A using the Sequenom MassArray platform. Furthermore, the effects of these variants were examined in correlation with phenotypic clinical features., Results: Heterozygous carriers for the variants C1236T, rs2235046 (an SNP in intron 16), and G2677T/A showed a lower risk of developing ulcerative colitis (C1236T: odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.42-0.93, P = 0.03; G2677T/A: OR = 0.59, CI = 0.39-0.89, P = 0.02; and rs2235046: OR = 0.59, 95% CI = 0.38-0.91, P = 0.009) as compared with homozygotes. None of the analyzed markers were associated with Crohn's disease on a genotypic level. Subgroup analysis revealed an association for 2 variants with IBD when stratified for age of onset (C1236T SNP and rs3789243). The MDR1 variant C3435T was associated with disease behavior in CD (OR = 1.45, 95% CI = 1.01-2.08, P = 0.04), whereas the SNP rs3789243 was found to be associated with pancolitis in UC patients (OR = 1.35, CI = 1.00-1.82, P = 0.05)., Conclusions: The results of our study support the role of MDR1 as a candidate gene for ulcerative colitis. Furthermore, our results suggest the possibility of a heterozygous advantage for certain MDR1 variants for this disease., (Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.)

Background: Human Paneth cell alpha-defensins, especially DEFA5, are involved in maintaining homeostasis of the human microbial microflora. Since breakdown of normal mucosal antibacterial defence occurs in inflammatory bowel disease (IBD), variants in the DEFA5 gene could be associated with IBD risk., Subjects: A cohort of 25 patients with indeterminate colitis (IC), 405 with ulcerative colitis (UC), and 385 with Crohn's disease (CD), were compared with 201 control individuals from the Canterbury region in New Zealand., Methods: A 15 kb haplotype block surrounding DEFA5 contained 35 HapMap markers which were polymorphic in Caucasians. Four markers (A-D) were selected to tag 27 of the 35 markers at r(2)>0.68, and were genotyped in DNA samples., Results: Minor allele frequencies for all single nucleotide polymorphisms (SNPs) were somewhat elevated in patients. Subgroup analysis showed SNP A had odds ratio 1.44 in UC patients with pancolitis (95% C.I. 1.07-1.94), SNP B odds ratio 2.37 in CD patients with onset prior to 17 years age (95% C.I. 1.12-5.03), SNP C odds ratio 1.68 in UC patients with left colonic localisation (95% C.I. 1.12-2.52), and SNP D had odds ratio 1.56 in CD patients with one or more relatives with IBD (95% C.I. 1.03-2.35). Two two-marker haplotypes and one three-marker haplotype were associated with UC (p-values 0.025-0.05)., Conclusions: The SNPs genotyped in our study were surrogates for common variants, and observed associations between these and IBD status are likely due to linkage disequilibrium with a functional common DEFA5 variant. Identifying such functional variants will be prioritized in subsequent work.

Around 9% of inflammatory bowel disease (IBD) patients are resistant to azathioprine. We hypothesized that these patients may carry mutations within inosine-5'-monophosphate dehydrogenase (IMPDH). To test this hypothesis, we screened 20 azathioprine-resistant patients for variations in the two IMPDH genes (IMPDH1 and IMPDH2) using dHPLC and DNA sequencing. A 9 bp insertion within the IMPDH1 P3 promoter was found in a patient exhibiting severe azathioprine resistance. The insertion is predicted to abolish a cAMP-response element (CRE) and was found to significantly reduce IMPDH1 P3 promoter activity in a luciferase reporter gene assay (P-value <0.001). This in vitro assay suggests the variant promoter has altered function in vivo and consequently may have contributed to the thiopurine resistance observed in this patient. The absence of functional variants within the other patients indicates that if IMPDH genetic variability contributes to azathioprine resistance it does so infrequently.

Background: Azathioprine and 6-mercaptopurine (6-MP) are well established for the treatment of inflammatory bowel disease (IBD). Assessing thiopurine methyltransferase (TPMT) status has been recommended to reduce the risk of serious toxicity. Measuring red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) concentrations has been recommended for dose adjustment., Aim: To describe the results of measuring TPMT activity and genotype, and 6-TGN concentration in New Zealand., Methods: Canterbury Health Laboratories provided these analyses for New Zealand. Those with low TPMT activity also underwent genotyping. All results were collated and analysed descriptively. 6-TGN concentrations were correlated with the dose of thiopurine when known., Results: TPMT enzyme activity (range 1-22 U/mL) from 574 patients showed a trimodal distribution. Genotyping results matched this distribution with only mild overlap between (*1/*1) homozygote and (*1/*3) heterozygote groups. One patient without TPMT measurement before therapy had life-threatening neutropenia and was later found to have (*3/*3) genotype. TPMT analysis probably prevented two further such cases. Of 884 6-TGN concentrations (range 0-1434 pmol/10(8) RBC), 41, 39 and 20% were within, below, and above the therapeutic range of 235-450 pmol/10(8) RBC, respectively. Leucopenia was seen in some patients with high 6-TGN. 6-MMP concentrations in 177 patients with low 6-TGN suggested non-compliance in 31, underdosing in 130, and preferential metabolism of 6-MP to 6-methylmercaptopurine in 16. There was poor correlation between azathioprine dose and 6-TGN concentration (r(2) = 0.002), supporting 6-TGN monitoring., Conclusions: Measurement of TPMT enzyme activity and 6-TGN concentration has been well-integrated into clinical practice. These tests should reduce the risk of toxicity and improve efficacy with thiopurines in patients with IBD.

Background: Azathioprine and mercaptopurine (MP) are well established treatments for inflammatory bowel disease but they have severe adverse effects that prevent their use in some patients. The likelihood and type of adverse effect may relate to thiopurine methyltransferase (TPMT) enzyme activity and genotype., Aim: To compare the TPMT genotype frequencies in patients with inflammatory bowel disease who have had severe adverse effects to those who tolerate azathioprine or MP (controls)., Methods: Patients with inflammatory bowel disease who had been treated with azathioprine or MP in Christchurch between 1996 and 2002 were identified. Patients with adverse effects, and controls, were invited to provide a peripheral blood sample for analysis of TPMT genotype. The genotype frequencies were then compared between the two groups., Results: Fifty-six patients were identified with adverse effects requiring cessation of therapy, of which 50 were genotyped. Reactions included allergic-type (25%), hepatitis (33%), nausea/vomiting (14%), bone marrow suppression (10%), pancreatitis (6%) and other (12%). Five of 50 patients with reactions had TPMT genotype *1/*3, one had *3/*3, and the rest had the wildtype genotype *1/*1. The patient with genotype *3/*3 had severe pancytopenia requiring hospitalization. Three of 50 controls had the *1/*3 genotype and the rest were *1/*1., Conclusions: The TPMT allele frequency in our population with inflammatory bowel disease is similar to that reported elsewhere. There was a slight trend for more frequent TPMT mutations in the patients with adverse reactions, but this was not statistically significant. Most patients with reactions did not have gene mutations.

OBJECTIVES:Perianal Crohn's disease (CD) affects around one-quarter of CD patients and represents a distinct disease phenotype. The objective of this study was to investigate a large population-based cohort of inflammatory bowel disease (IBD) patients to identify clinical and genetic risk factors for perianal CD.METHODS:Data were collected in the Canterbury IBD database, estimated to include 91% of all patients with IBD in Canterbury, New Zealand. Genotyping was performed for selected loci previously demonstrated to be associated with CD. Patients with perianal disease were then compared with both CD patients without perianal disease and healthy controls to assess the presence of potential phenotypic, environmental, and genetic risk factors.RESULTS:Of the 715 CD patients in the database, 190 (26.5%) had perianal disease. In all, 507 patients with genotype data available were analyzed. Perianal disease was associated with younger age at diagnosis (P<0.0001), complicated intestinal disease (P<0.0001), and ileal disease location (P=0.002). There was no association with gender, ethnicity, smoking, or breast feeding. Genotype analysis revealed an association with the neutrophil cytosolic factor 4 (NCF4) gene compared with both non-perianal CD patients (odds ratio (OR): 1.47; 95% confidence interval (CI): 1.08-1.99) and healthy controls (OR: 1.47; 95% CI: 1.10-1.95). There was no association identified with other genes, including IBD5 (OR: 0.91; 95% CI: 0.69-1.20), tumor necrosis factor α (OR: 1.04; 95% CI: 0.56-1.85), and IRGM (immunity-related guanosine triphosphatase protein type M) (OR: 1.21; 95% CI: 0.80-1.82).CONCLUSIONS:This study suggests that younger age at diagnosis, complicated disease behavior, and ileal disease location are risk factors for perianal CD. In addition, this paper represents the first report of an association of the NCF4 gene with perianal disease. [ABSTRACT FROM AUTHOR]

The article presents a study which determined the perianal surgical intervention's (PSI) characteristics and frequency for Crohn's disease in patients with inflammatory bowel disease (IBD). The study was conducted in Canterbury, New Zealand where clinical notes on 1,421 patients were utilized. Results revealed that patients afflicted with Crohn's disease who were diagnosed at an early age experience PSI.

The location of CARD8 within an inflammatory bowel disease (IBD) locus and its role in the NALP3 inflammasome and as a nuclear factor (NF)κB inhibitor make it an attractive candidate risk gene for IBD. However, studies testing for the association of the CARD8 loss-of-function single-nucleotide polymorphism (SNP) rs2043211 with IBD have yielded mixed results. A recent study provided evidence that this discordance may result from an interaction of rs2043211 with loss-of-function variants in nucleotide-binding oligomerization domain protein 2 (NOD2) and a gain-of-function SNP (rs35829419) in NALP3. To confirm this interaction, we conducted a replication in an independent IBD sample set (n=1009 patients, n=517 controls). We found that the presence of the minor allele of rs2043211 with the major allele of rs35829419 conferred a protective effect against Crohn's disease (and vice versa), which intensified in the absence of NOD2 mutations (P1,2/1,1=0.009, odds ratio (OR)=0.66, 95% confidence interval (CI) (0.48–0.90); P1,1/1,2=0.015, OR=0.35, 95% CI (0.15–0.82)). We propose that these genotype combinations protect against gut inflammation by preventing the NALP3 inflammasome from producing excessive interleukin-1β. [ABSTRACT FROM AUTHOR]

The authors discuss a study published in an issue of the periodical focusing on the role of vedolizumab in treatment and cause of extra-intestinal manifestations of inflammatory bowel disease. Topics discussed include the lesions such as pyoderma gangrenosum, erythema nodosum and aphthous stomatitis; the prevalence of peripheral arthritis, ankylosing spondylitis and sacroiliitis; and the lack of efficacy of anti-rheumatic agents (DMARDs) such as methotrexate and sulphasalazine in treatment.

Reports a case of Mycobacterium avium paratuberculosis (MAP) infection in Crohn's disease patients. Hypotheses on the cause Crohn's disease; Characteristics of MAP; Performance of a duplex polymerase chain reaction to confirm the identity of the organism.