Issue Highlights

Abstract

Although the introduction of biologics for the treatment of Crohn’s in 1998 revolutionized our approach to this disease, primary non-response and secondary loss of response remain vexing problems for a large subset of patients in clinical practice. For anti-TNF agents, common reasons for loss of response include subtherapeutic drug concentrations and development of neutralizing anti-drug antibodies. Therapeutic drug monitoring, dose escalation and interval shortening are approaches with demonstrated effectiveness recapturing response to these agents and are commonly employed in clinical practice. 1 Papamichael K. Cheifetz A.S. Melmed G.Y. et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019; 17: 1655-1668.e3 Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Shortening the dose interval or dose intensification for Vedolizumab has also been shown to permit recapturing of response in some patients, 2 Peyrin-Biroulet L. Danese S. Argollo M. et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with crohn's disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019; 17: 838-846.e2 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar but whether this approach can be extrapolated to Ustekinumab remains unclear. This retrospective study by Ollech et al 3 Ollech J.E. Normatov I. Peleg N. et al. Effectiveness of Ustekinumab dose escalation in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2021; 19: 104-110 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar is the first to evaluate real-world effectiveness of interval shortening from 8- to 4-week dosing for Ustekinumab. The authors describe pre- and post-dose escalation parameters including Harvey Bradshaw Index (HBI), C-reactive protein (CRP), and fecal calprotectin for a subset of 110 patients not responding to Ustekinumab every 8 weeks. Although not all patients in the subset had all parameters pre- and post-dose increase, of the 78 patients (71%) with pre-and post-HBI metrics, the median HBI decreased from 4.5 to 3 (P = .002). Of 60 patients (55%) with CRP measurements, median CRP decreased from 8 mg/L to 3 mg/L (P = .031). Among patients with HBI >4, CRP ≥5 mg/L, fecal calprotectin >250 μg/g, or endoscopic evidence of active disease, 28% achieved clinical remission (HBI<4), 22% normalized CRP, and 36% endoscopic remission with a median follow up of 9 months post-dose increase. 38% of patients on steroids were able to discontinue, and 45% with active perianal disease reported resolution within 6 months of dose-escalation. Twenty-three patients (20.9%) discontinued therapy following dose escalation, most (78%) due to lack of response; only 1 due to side effects (rash). This is the first study to demonstrate improvement in objective measures of Crohn’s disease activity with dose-intensification of Ustekinumab from 8- to 4-week intervals. Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn’s DiseaseClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewA subset of patients with Crohn’s disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. Full-Text PDF Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis–Related, Child–Pugh A CirrhosisClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewFactors that affect outcomes of patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use of antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. Full-Text PDF Intragastric Balloon Placement Induces Significant Metabolic and Histologic Improvement in Patients With Nonalcoholic SteatohepatitisClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewObese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. Full-Text PDF Serum Levels of α-Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular CarcinomaClinical Gastroenterology and HepatologyVol. 19Issue 1PreviewUltrasound (US)-based screening has been recommended for patients with an increased risk of hepatocellular carcinoma (HCC). US analysis, however, is limited in patients who are obese or have small tumors. The addition of serum level of α-fetoprotein (AFP) measurements to US analysis can increase detection of HCC. We analyzed data from patients with chronic liver disease, collected over 15 years in an HCC surveillance program, to develop a model to assess risk of HCC. Full-Text PDF