Real-World Experience With Proactive Therapeutic Drug Monitoring During Infliximab Reintroduction.

Background: Interruptions in infliximab therapy are associated with the development of antibodies to infliximab (ATI), infusion reactions (IRs), and loss of response. Despite these challenges, recent observational studies suggest that reinitiating infliximab after a drug holiday can be safe and effective. We assessed the utility of our protocol for restarting infliximab using early serum infliximab and ATI measurements. Methods: A retrospective cohort study of patients restarted on infliximab after at least a 6-month drug holiday. The cohort was divided into 2 groups: a "therapeutic drug monitoring (TDM) group," those who had serum infliximab and ATI measured 1-3 weeks after first reinduction dose, and a "non-TDM group." Outcomes included results of TDM, occurrence of immediate IR (IIR) and delayed hypersensitivity reactions, and medication persistence at 14 weeks and 1 year. Results: About 76 patients were included: 49 in the TDM group and 27 in the non-TDM group. Of 76, 67 (88%) patients tolerated the first reinduction dose without IR. Formation of ATI was seen in 17 of 49 (35%) patients and was associated with longer drug holidays. Most did not experience IR during the entire therapy course-in 26 of 32 (81%) without ATI and 20 of 27 (74%) in the non-TDM group. Infliximab persistence at 14 weeks and 1 year was 76% and 57% for the cohort, respectively. Conclusion: Infliximab can be safely and effectively restarted after a drug holiday. We suggest performing TDM with a drug-tolerant assay 1-3 weeks after the first reinduction infusion as a means to identify patients at risk for severe IIR at the second dose.

Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn's Disease.

BACKGROUND & AIMS: A 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. METHODS: We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%). RESULTS: Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 µg/g to 157 µg/g (P = .57). Among patients who had an HBI >4, a level of CRP ≥5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. CONCLUSIONS: Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.

Efficacy of biosimilar infliximab CT-P13 among inpatients with severe steroid-refractory colitis.

INTRODUCTION: In this study, we evaluate the efficacy and safety of the biosimilar infliximab, CT-P13, in the treatment of inpatients with severe steroid-refractory colitis. METHODS: A retrospective cohort study of adult colitis patients (UC or isolated Crohn's colitis) admitted to the University of Chicago inflammatory bowel disease inpatient service between January 2018 and December 2018 for management of severe colitis refractory to IV steroids who received CT-P13 were included in the study. Patients diagnosed with active small bowel Crohn's disease were excluded. CT-P13 was given as a single infusion of 5 to 10 mg/kg. A comprehensive review of their electronic medical records was performed, and demographic, clinical, laboratory, and endoscopic data were extracted. The primary endpoint was colectomy-free survival. RESULTS: Twenty-one patients with severe steroid-resistant colitis were included. Twelve patients had ulcerative colitis, seven patients had a diagnosis of indeterminate colitis, and two patients had a diagnosis of Crohn's colitis. The median age was 32.2 years. The median disease duration was 4.3 years, and the median follow-up time was 5.9 months. Patients had a median CRP of 23. All patients had moderate to severe disease on endoscopy. Colectomy-free survival was 76% at 3 months and 70% at 6 months. No severe adverse events were reported in this patient cohort. CONCLUSION: A significant proportion of patients with severe colitis failing IV steroids responded to induction therapy with CT-P13. Colectomy-free survival rates were similar to previous randomized trials using originator infliximab as induction therapy in severe steroid-refractory colitis.

Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid-refractory ulcerative colitis.

BACKGROUND: Following induction therapy with a calcineurin inhibitor (CNI) in severe ulcerative colitis, transitioning to vedolizumab as maintenance therapy could be an option. AIM: To report on the largest cohort of patients successfully induced with CNIs who were transitioned to vedolizumab maintenance therapy. METHODS: This is a retrospective observational study of adult patients with severe steroid-refractory ulcerative colitis. Patients were included if they were induced with a CNI followed by maintenance therapy with vedolizumab between January 2014 and December 2018. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14. RESULTS: A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with CNIs for severe steroid-refractory colitis. Patients were followed for a median time of 25 months (IQR 16-36). Colectomy-free survival rates from vedolizumab initiation were 93% at 3 months, 67% at 1 year and 55% at 2 years. At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At 1 and 2 years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab respectively. Vedolizumab was dose escalated to infusions every 4 weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1-8.2). No serious adverse events were recorded in our patient cohort. CONCLUSIONS: Transitioning to vedolizumab following induction of remission with CNIs is effective and safe.

Pancreatic Malnutrition in Children.

Exocrine pancreatic insufficiency in children can lead to lifelong complications related to malnutrition and poor growth. The clinical presentation can be subtle in the early stages of insufficiency as the large functional capacity of the pancreas is gradually lost. The pediatrician plays a crucial role in the early identification of these children to ensure a timely referral so that a diagnosis can be made and therapy initiated. Early nutritional therapy allows for prevention and correction of deficiencies, which leads to improved outcomes and survival. When insufficiency is suspected, the workup should start with an indirect test of exocrine pancreatic function, such as fecal elastase, to establish the diagnosis. Once a diagnosis is established, further testing to delineate the etiology should be pursued, with cystic fibrosis being high on the differential list and assessed for with a sweat test. Assessment of anthropometry at every visit is key, as is monitoring of laboratory parameters and physical examination findings that are suggestive of malabsorption and malnutrition. The mainstay of management is administration of exogenous pancreatic enzymes to facilitate digestion and absorption. [Pediatr Ann. 2019;48(11):e441-e447.].

Differential risk of disease progression between isolated anastomotic ulcers and mild ileal recurrence after ileocolonic resection in patients with Crohn's disease.

BACKGROUND AND AIMS: It is standard of care to perform ileocolonoscopy within a year of ileocolonic resection for Crohn's disease (CD) and to guide management decisions based on the Rutgeert score (RS). The modified RS subdivides i2 into lesions confined to the anastomosis (i2a) or >5 aphthous lesions in the neoterminal ileum (i2b). There is uncertainty, however, if i2a lesions incur an increased risk of disease recurrence. The primary aim of this study was to compare the rates of endoscopic progression between i2a and i2b when compared with i0-i1. METHODS: This was a retrospective, single-center study including patients with CD who had an ileocolonoscopy ≤12 months after ileocolonic resection with primary anastomosis and who had >1 year of documented clinical follow-up after the index endoscopic evaluation. All consecutive eligible patients between 2004 and 2014 were included in the study. Demographic, disease, and treatment data were collected. Patients with i3 or i4 at index colonoscopy were excluded from further analyses. Outcomes included endoscopic progression and recurrent surgery. For patients with RS of i0 to i2, endoscopic progression was predefined as progression of the RS in subsequent colonoscopies to i3 or i4. Recurrent surgical interventions were defined as re-resection or stricturoplasty of the previous ileocolonic anastomosis. RESULTS: Two hundred seven CD patients (median age, 36 years [interquartile range, 26-48]) had an ileocolonoscopy ≤12 months after ileocolonic resection. At index colonoscopy, 95 patients (45.9%) had an RS of i0, 31 (14.9%) i1, 40 (19.3%) i2a, 25 (12.1%) i2b, 10 (4.8%) i3, and 6 (2.9%) i4. One hundred ninety-one patients had an RS of i0 to i2 and were included in the analyses for recurrent surgery. One hundred forty-nine patients had a second endoscopic evaluation and were included in the analysis for the primary outcome of endoscopic disease progression. Kaplan-Meier analyses were performed and found the hazard ratio (HR) of endoscopic progression to be significantly higher with i2b lesions when compared with i0 or i1 (HR, 6.22; 95% confidence interval [CI], 2.38-16.2; P = .0008). Patients with i2a did not have significantly higher rates of endoscopic progression when compared with i0 or i1 (HR, 2.30; 95% CI, .80-6.66; P = .12). Likewise, patients with i2b lesions had higher risk of needing recurrent surgery when compared with i0 or i1 (HR, 3.64; 95% CI, 1.10-12.1; P = .034), whereas patients with i2a lesions were not found to have a significantly elevated risk of recurrent surgery (HR, 1.43; 95% CI, .35-5.77; P = .62). CONCLUSION: Endoscopic lesions limited to the ileocolonic anastomosis (RS i2a) in patients with CD undergoing colonoscopy within 1 year of their resection were not associated with a significantly higher rate of progression to more severe disease, whereas those in the neoileum (RS i2b) were. Prospective studies are needed to confirm these findings.

Nutrition in Pediatric Chronic Liver Disease.

More than one-half of children with chronic liver disease suffer from malnutrition, which leads not only to a poor quality of life and even possibly catastrophic complications, but also to poor outcomes after a liver transplantation. These children have increased metabolic demands but often decreased intake with malabsorption and altered nutrient utilization, all of which make it difficult to keep up with nutritional demands. Assessment of a patient's nutritional status should be timely, and it should be performed routinely and proactively. When specific nutritional needs are identified, these should be addressed with a multidisciplinary team approach and with the close guidance of an experienced pediatric dietician. The assessment includes anthropometric and laboratory assessments, in addition to a careful physical examination and a detailed patient history. The specific nutritional needs vary, but generally dietary intervention focuses on increasing caloric intake, supplementation with medium-chain triglycerides, and prevention of essential fatty acid and fat-soluble vitamin deficiencies. [Pediatr Ann. 2018;47(11):e445-e451.].

Perisigmoid Abscess Leading to a Diagnosis of Ehlers-Danlos Syndrome Type IV.

The Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders characterized by triad of joint hypermobility, skin extensibility, and tissue fragility. Ehlers-Danlos syndrome type IV places patients at risk for life-threatening, spontaneous, vascular or visceral rupture due to reduced or abnormal secretion of type III collagen. We present an adolescent male who was found to have a perisigmoid abscess with a fistula connecting to adjacent sigmoid colon secondary to undiagnosed EDS type IV. Conservative management with antibiotics and bowel rest was pursued to allow for elective resection for his acute complicated diverticulitis at a safer time.