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Background & aimsSome women with inflammatory bowel disease require therapy with tumor necrosis factor (TNF) antagonists during pregnancy. It is not clear whether these drugs are transferred to the fetus via the placenta and then cleared, or whether structurally different TNF antagonists have different rates of transfer.MethodsWe studied 31 pregnant women with inflammatory bowel disease receiving infliximab (IFX, n = 11), adalimumab (ADA, n = 10), or certolizumab (CZP, n = 10). Serum concentrations of the drugs were measured at birth in the mother, infant, and in cord blood, and then monthly in the infant until the drugs were undetectable. Drug concentrations in the cord and the infant at birth were compared with those of the mother.ResultsConcentrations of IFX and ADA, but not CZP, were higher in infants at birth and their cords than in their mothers. The levels of CZP in infants and their cords were less than 2 μg/mL. The median level of IFX in the cord was 160% that of the mother, the median level of ADA in the cord was 153% that of the mother, and the median level of CZP in the cord was 3.9% that of the mother. IFX and ADA could be detected in the infants for as long as 6 months. No congenital anomalies or serious complications were reported.ConclusionsThe TNF antagonists IFX and ADA are transferred across the placenta and can be detected in infants at birth; the drugs were detected in infants up to 6 months after birth. CZP has the lowest level of placental transfer, based on levels measured in cords and infants at birth, of the drugs tested.

Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4–9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30–1.68; P =.009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P =.15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P =.003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov , Number: NCT02447302 [ABSTRACT FROM AUTHOR]

The initial diagnosis of inflammatory bowel disease (IBD) requires multiple diagnostic modalities; however, endoscopic evaluation as a diagnostic test is considered the gold standard. Endoscopic evaluation includes colonoscopy with ileoscopy, esophagogastroduodenoscopy, enteroscopy, and capsule endoscopy. IBD encompasses Crohn’s disease, ulcerative colitis, and IBD unclassified. Colonoscopy with ileoscopy along with biopsy collection is essential in most IBD cases for diagnosis and to rule out alternative findings that may mimic IBD including ischemia, diverticulitis, segmental colitis associated with diverticulosis, neoplasia, radiation enteritis, and drug-induced colitis. Esophagogastroduodenoscopy, enteroscopy, and capsule endoscopy are used in the initial workup of specific groups of patients with IBD. The role of endoluminal diagnostic studies in the initial diagnosis of IBD is discussed in detail in this article. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Anti-tumor necrosis factors (anti-TNF) including infliximab, adalimumab and certolizumab pegol are used to treat Crohn's disease (CD) and ulcerative colitis (UC). Paradoxically, while also indicated for the treatment of psoriasis, anti-TNF therapy has been associated with development of psoriasiform lesions in IBD patients and can compel discontinuation of therapy. We aim to investigate IBD patient, clinical characteristics, and frequency for the development of and outcomes associated with anti-TNF induced psoriasiform rash. Methods: We identify IBD patients on anti-TNFs with an onset of a psoriasiform rash. Patient characteristics, duration of anti-TNF, concomitant immunosuppressants, lesion distribution, and outcomes of rash are described. Results: Of 1004 IBD patients with exposure to anti-TNF therapy, 27 patients (2.7%) developed psoriasiform lesions. Psoriasiform rash cases stratified by biologic use were 1.3% for infliximab, 4.1% for adalimumab, and 6.4% for certolizumab. Average time on treatment (206.3weeks) and time on treatment until onset of psoriasiform lesions (126.9weeks) was significantly higher in the infliximab group. The adalimumab group had the highest need for treatment discontinuation (60%). The majority (59.3%) of patients were able to maintain on anti-TNFs despite rash onset. Among patients that required discontinuation (40.7%), the majority experienced improvement with a subsequent anti-TNF (66.7%). Conclusion: 27 cases of anti-TNF associated psoriasiform lesions are reported. Discontinuation of anti-TNF treatment is unnecessary in the majority. Dermatologic improvement was achieved in the majority with a subsequent anti-TNF, suggesting anti-TNF induced psoriasiform rash is not necessarily a class effect. [Copyright &y& Elsevier]

Pediatric severe ulcerative colitis that is resistant to current medical treatment can successfully be managed surgically with a colectomy, ileal pouch creation and pouch-anal anastomosis. Key issues that should be considered and discussed before the pouch option can be offered include alternative surgical procedures, pouch function expectations, risk of surgical leak, pelvic sepsis, anastomotic strictures, acute and chronic pouch inflammation, Crohn's disease of the pouch and risk of reduced fertility for females. A long-term risk is malignancy of the residual colonic tissue. The decision to proceed with a pouch or not poses a substantial emotional burden to the child and family. Despite the risk of surgical complications and pouch inflammatory and functional challenges, the overwhelming majority of children and their families are satisfied with their pouch surgery outcomes. Further study is needed to assess preoperative risk predictors, prevention and treatment of complications. [ABSTRACT FROM AUTHOR]

Oral therapies targeting the integrin α4β7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4β7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC). In vitro studies measured binding properties of PTG-100. Mouse studies measured biomarkers and drug concentrations in blood and tissues. The phase 1 study involved healthy volunteers. In phase 2a, patients with moderate to severe active UC were randomized to receive PTG-100 (150, 300, or 900 mg) or placebo once daily for 12-weeks. PTG-100 potently and selectively blocks α4β7. Oral dosing of PTG-100 in mice showed high levels of target engagement and exposure in gut-associated lymphoid tissues. In healthy volunteers, PTG-100 showed dose-dependent increases in plasma exposure and blood target engagement. Although this phase 2a study initially did not meet the primary endpoint, a blinded reread of the endoscopy videos by a third party indicated clinical efficacy in conjunction with histologic remission at doses correlating with less than 100% receptor occupancy in peripheral blood. PTG-100 showed local gastrointestinal tissue target engagement and inhibition of memory T-cell trafficking in mice. It was safe and well tolerated in phase 1 and 2 studies. Phase 2a data are consistent with biological and clinical response and showed a dose response reflecting similar activities in preclinical models and healthy individuals. These data suggest that local gut activity of an oral α4β7 integrin antagonist, distinct from full target engagement in blood, are important for efficacy and the treatment of UC. (ClinicalTrials.gov , Number NCT02895100; EudraCT, Number 2016-003452-75) [Display omitted] PTG-100 shows proof of principle for an oral therapy with limited systemic absorption in patients with ulcerative colitis. PTG-100 was well tolerated in patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

The article describes the case of a 31-year-old male maintenance supervisor who developed ulcerative colitis. Frequent bloody diarrhea, abdominal cramping and colonoscopy formed the basis of the diagnosis. Epigastric pain was experienced by the patient which did not radiate and was not associated with food ingestion. Particular focus is given to the results of computed tomography, flexible sigmoisdoscopy and biopsies.

The authors undertook retrospective cross-sectional study to determine the relationship between the use of ursodiol and dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis (PSC). All patients with ulcerative colitis and PSC were evaluated for the presence of dysplasia in biopsies taken during a previously established colonoscopic surveillance program. In the program, patients underwent colonoscopy every 3 yr with random four-quadrant biopsies (average of 47 biopsies/session). If low grade dysplasia indefinite for dysplasia or aneuploidy was found at any time, patients then had yearly colonoscopies. Patients were included in the ursodiol group if they had used ursodiol at any time before the development of dysplasia. The primary endpoint was the development of dysplasia. Fifty-nine patients met the entry criteria. Of these, 41 had taken ursodiol at some time and 18 had never taken ursodiol. The development of dysplasia was significantly less common in patients who had received ursodiol (odds ratio = 0.18, 95% CI = 0.05-0.61). The development of dysplasia was not related to other medications, including sulfasalazine, 5-aminosalicylic acid, prednisone, cyclosporine, azathioprine, and methotrexate. The protective effect of ursodiol against the development of dysplasia remained after adjusting for sex, age at onset of colitis, duration of colitis, duration of PSC, Child-Pugh class, and use of sulfasalazine. An increased risk for the development of dysplasia was also noted in those patients who had onset of colitis at a younger age. The authors concluded that ursodiol use is associated with lower frequency of colonic dysplasia in patients with ulcerative colitis and PSC. They suggest that a prospective randomized trial evaluating the chemoprotective effect of ursodiol is warranted. [ABSTRACT FROM AUTHOR]