Open Peer Review Any reports and responses or comments on the article can be found at the end of the article. RESEARCH ARTICLE Augmented ustekinumab dosing is needed to achieve clinical response in patients with anti-TNF refractory pediatric Crohn’s disease: a retrospective chart review [version 1; peer review: 1 approved with reservations] Phinga Do , John Andersen , Ashish Patel , Gaith Semrin , Luis Sifuentes-Dominguez , Phuong Luu , Bhaskar Gurram 1,2 Department of Pediatrics, Children’s Health Medical Center Dallas, Dallas, TX, 75235, USA Department of Pediatric Gastroenterology, UT Southwestern Medical Center, Dallas, TX, 75235, USA Abstract Ustekinumab is a monoclonal antibody that inhibits Background: interleukins 12 and 23. It is approved for treatment of Crohn’s disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. We performed a retrospective chart review on pediatric patients Methods: with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient’s clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. We identified 10 patients with CD who were started on Results: ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of <4.5 μg/mL while on standard maintenance dosing every 8 weeks, and four patients showing therapeutic drug levels of >4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. In this retrospective chart review, 7 out of 10 patients with Conclusion: anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD. Keywords Ustekinumab, Pediatric Crohn's disease, anti-TNF-refractory Crohn's disease, Inflammatory bowel disease, Therapeutic drug monitoring, Clinical response 1 1,2 1,2 1,2 1,2 1 1,2 1 2 Reviewer Status Invited Reviewers version 1 30 Apr 2020 1 report , Baylor College of Richard Kellermayer Medicine, Houston, USA Texas Children's Hospital, Houston, USA USDA/ARS Children's Nutrition Research Center, Houston, USA 1 30 Apr 2020, :316 First published: 9 https://doi.org/10.12688/f1000research.22673.1 30 Apr 2020, :316 Latest published: 9 https://doi.org/10.12688/f1000research.22673.1 v1 Page 1 of 12 F1000Research 2020, 9:316 Last updated: 18 MAY 2020