Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.)

We compared the incidence of appendicitis or appendectomy across the world and evaluated temporal trends. Population-based studies reported the incidence of appendicitis. We searched MEDLINE and EMBASE databases for population-based studies reporting the incidence of appendicitis or appendectomy. Time trends were explored using Poisson regression and reported as annual percent change (APC) with 95% confidence intervals (CI). APC were stratified by time periods and pooled using random effects models. Incidence since 2000 was pooled for regions in the Western world. The search retrieved 10,247 citations with 120 studies reporting on the incidence of appendicitis or appendectomy. During the 21st century the pooled incidence of appendicitis or appendectomy (in per 100,000 person-years) was 100 (95% CI: 91, 110) in Northern America, and the estimated number of cases in 2015 was 378,614. The pooled incidence ranged from 105 in Eastern Europe to 151 in Western Europe. In Western countries, the incidence of appendectomy steadily decreased since 1990 (APC after 1989=−1.54; 95% CI: −2.22, −0.86), whereas the incidence of appendicitis stabilized (APC=−0.36; 95% CI: −0.97, 0.26) for both perforated (APC=0.95; 95% CI: −0.25, 2.17) and nonperforated appendicitis (APC=0.44; 95% CI: −0.84, 1.73). In the 21st century, the incidence of appendicitis or appendectomy is high in newly industrialized countries in Asia (South Korea pooled: 206), the Middle East (Turkey pooled: 160), and Southern America (Chile: 202). Appendicitis is a global disease. The incidence of appendicitis is stable in most Western countries. Data from newly industrialized countries is sparse, but suggests that appendicitis is rising rapidly. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract.