American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases

Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor-α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti-tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab

Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients with Crohnʼs Disease: A Randomized, Double-blind, Placebo-controlled Pilot Study

The commensal bacterial flora plays a critical role in postoperative recurrence of Crohn’s disease (CD). We conducted a randomized, double-blind, placebo-controlled 6 months pilot trial of ciprofloxacin for the prevention of endoscopic recurrence in patients with CD who underwent surgery

Caustic ingestion management : world society of emergency surgery preliminary survey of expert opinion

Caustic material ingestion injuries (CMI) are uncommon. Only 5,000 cases are reported in the United States each year and most acute care healthcare facilities admit only a few cases annually. Accordingly, no single institution can claim extensive experience, and management protocols are most probably based on either expert opinion or literature reports. In this study, we will attempt to review opinions and practices of representatives of the board members of the World Society of Emergency Surgery and compare them to the current literature.Peer reviewe

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Surgical Cost of Care in Crohn’s Disease

The aim of the studywas to evaluate the cost of surgical care and short-term outcomes of Crohn’s disease(CD) in the era of laparoscopy and biologic therapy. Material and methods. Review of a prospective database identifiedCD patients that underwent surgical management. Patients were stratified into laparoscopic, open, and converted approaches. Main outcome measures were short-term patient outcomes and cost of care by approach. Results. 92 patients were analyzed- 63.1% laparoscopic, 32.6% open, 4.3% converted. The majority was elective (100% converted, 94.8% laparoscopic, 90% open) and segmental resections (75% converted, 70.7% laparoscopic, 43.3% open). Operative times were similar between laparoscopic and open (152 minutes and 138 minutes, respectively). More open patients required ICU care (20% versus 12.1% laparoscopic and 0% converted). The median LOS was 3 (1-25) days laparoscopic, 4 (1-29) open and 4 (3-8) converted. The laparoscopic complication rate was 15.5%, readmission rate 12.1%, and reoperation rate 8.6%. The mean total hospital cost was $9,702 laparoscopic,$10,782 open, and $13,293 for converted cases (US Dollars). Conclusions. Laparoscopy is appropriate for most CD cases. When necessary to combine with open surgery, this results in efficient and effective patient outcomes and healthcare utilization. These results are important when weighing the cost of ongoing medical therapy versus surgical intervention