Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

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.

Review article: acute severe ulcerative colitis - evidence-based consensus statements.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM: To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS: Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS: Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION: These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.

Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis.

BACKGROUND: Smoking demonstrates divergent effects in Crohn's disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC is primarily a disease of nonsmokers and ex-smokers, with reports of disease amelioration in active smoking. AIM: To determine the prevalence of smoking and its effects on disease progression and surgery in a well-characterised cohort of inflammatory bowel diseases (IBD) patients. METHODS: Patients with smoking data of the Sydney IBD Cohort were included. Demographic, phenotypic, medical, surgical and hospitalisation data were analysed and reported on the basis of patient smoking status. RESULTS: 1203 IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672 patient-years of follow-up, respectively. CD patients were more likely to smoke than UC patients (19.2% vs. 10.2%, P < 0.001). A history of smoking in CD was associated with an increased proportional surgery rate (45.8% vs. 37.8%, P = 0.045), requirement for IBD-related hospitalisation (P = 0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet no reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital admission (P = 0.25) relative to nonsmokers. Ex-smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and never smokers. CONCLUSIONS: This study confirms the detrimental effects of smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC. These data should encourage all patients with IBD to quit smoking.

Obstetric performance of women who have previously delivered a baby of low birthweight.

OBJECTIVES: To investigate pregnancy outcomes in women who have previously given birth to a baby weighing less than 2500 grams in a population in which the low birthweight rate is high. METHODS: We compared the obstetric performance of 100 women who had delivered a low birthweight baby (<2500g) at term in a previous pregnancy (cases) with those of 100 women who were matched for age, height, body mass index at booking, parity and medical disorders, who had previously delivered a baby above that threshold (controls). RESULTS: We found the following significant differences between cases and controls (p<0.001 for all). Gestation at delivery (mean±SD = 38.0±1.9 vs. 39.1 ± 1.2 weeks); risk of delivery before completion of 37 weeks (19.0% vs. 3.0%); birthweight (mean±SD = 2.553 ± 0.444 vs. 3.015 ± 0.413 Kg); risk of delivery of a low birthweight (LBW) baby in the current pregnancy (27.0% vs. 4.0%). The stillbirth rate was also significantly higher among cases (4 vs. 0; p<0.05). CONCLUSIONS: Birth of a LBW baby points to adverse events in future pregnancies even where its prevalence is high. It is a useful criterion for assessment of risk in antenatal care and for directed interventions.

Complete Barrett's excision by stepwise endoscopic resection in short-segment disease: long term outcomes and predictors of stricture.

BACKGROUND AND STUDY AIMS: Complete Barrett's excision (CBE) of short-segment Barrett's high grade dysplasia (HGD) and early esophageal adenocarcinoma by stepwise endoscopic resection is a precise staging tool, detects covert synchronous disease, and may produce a sustained treatment response. Esophageal stricture is the most commonly reported complication of CBE although risk factors have not yet been clearly defined. PATIENTS AND METHODS: Data were recorded prospectively on patients with limited co-morbidity and age ≤ 80 years undergoing CBE for histologically proven HGD or esophageal adenocarcinoma within ≤ C3M5 segments. Endoscopic resection was performed by standardized protocol every 6 - 8 weeks until CBE was achieved. Esophageal dilation was performed when patients reported dysphagia. Dysphagia scores were recorded at scheduled endoscopic surveillance or by telephone interview. RESULTS: By intention-to-treat analysis, complete eradication of neoplasia and intestinal metaplasia was achieved in 95 % and 82 %, respectively, in 77 patients undergoing a median of 2 resection sessions (interquartile range [IQR] 1 - 3). Esophageal dilation was required in 33 % (median 3 dilations, IQR 1 - 3.5) at median follow-up of 20 months (IQR 6 - 40). Independent risk factors for dilation requirement were the number of mucosal resections at the index procedure (odds ratio [OR] 1.3 per resection, 95 % confidence interval [CI] 1.0 - 1.9; P = 0.043) and maximal extent of the Barrett's segment (OR 2.2 per cm, 95 %CI 1.2 - 3.9; P = 0.009). CONCLUSIONS: Although CBE is highly effective in the treatment of Barrett's HGD and esophageal adenocarcinoma, the risk of post-CBE dysphagia increases with the maximal extent of the Barrett's segment and the number of mucosal resections at the index procedure. These data could be used to inform treatment decisions and identify those patients who may benefit from prophylactic therapies such as dilation.