Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis.

OBJECTIVES: Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS: We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS: Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS: UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

Direct transition from rapid-infusion originator to rapid-infusion biosimilar tumor necrosis factor inhibitor in children with inflammatory bowel disease: A case series.

PURPOSE: Biosimilar tumor necrosis factor inhibitors (b-TNFi) reduce healthcare costs and maintain equal efficacy when compared to their originator counterparts (o-TNFi). Current practice is to start patients on a slower standard infusion rate during the initial transition from an o-TNFi to a b-TNFi. There is a knowledge gap around switching from rapid originator infusion to rapid biosimilar infusion in the pediatric inflammatory bowel disease (IBD) population. SUMMARY: We present a case series of 8 pediatric patients with IBD who were switched from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi from 2016 through 2022. Our primary interest was safety, which we evaluated based on the occurrence of infusion reactions or need for new premedications within the first 6 months of starting a b-TNFi. We also examined effectiveness through the incidence of IBD-related hospitalizations, TNFi failure, and need for co-medication or dose escalation over the same period. In our cohort, 4 patients had Crohn's disease and 4 had ulcerative colitis. All patients were switched to a biosimilar for nonmedical reasons. During the follow-up period, no patients had infusion reactions necessitating new premedications, serious adverse events, or medication nonresponse. CONCLUSION: Patients who directly transitioned from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi did not experience serious adverse events. Given the fiscal and patient experience advantages of rapid-rate infusions, larger studies are needed to consider a change in practice.

Evaluating the Relationship Between Nutrition and Post-colectomy Pouchitis in Pediatric Patients with Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p < 0.01) between the first two stages. A positive trend in BMI-for-age Z-scores (p = 0.08) was identified in children with 2-stage procedures. All patients showed sustained nutritional improvement during the follow-up period. Among patients who underwent 3-stage surgeries, BMI worsened by 0.8 standard deviations (SDs) (p = 0.24) between the initial stages in those who developed recurrent or chronic pouchitis and improved by 1.1 SDs (p = 0.04) in those who did not. CONCLUSIONS: Early improvement in BMI-for-age Z-scores following the initial stage was associated with lower rates of recurrent or chronic pouchitis. Larger prospective studies are needed to validate these findings.

Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease.

INTRODUCTION: Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited. AIM: We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD. Adverse events were documented. METHODS: We identified 40 pediatric patients with CD treated with UST between January 1, 2016 and December 31, 2019. Electronic medical records were reviewed for demographics, Paris Classification, significant comorbidities, previous CD therapy, adverse events after initiation, and surveillance markers at the time of their first dose and most recent clinic visit. A validated abbreviated pediatric CD activity index (aPCDAI) was used to assess response to therapy. RESULTS: Thirty-eight pediatric patients with CD, including 34.2% with stricturing or penetrating disease, were analyzed after initiation of treatment with UST. Median age at diagnosis of CD was 12.5 years, and median age at UST induction was 17.2 years. No patients were anti-TNF-naive, and 34.2% were previously exposed to 2 or more anti-TNF agents. At time of last follow-up, 84.2% of patients remained on UST for a median duration on UST of 62.1 weeks, and 60.5% achieved clinical remission. Patients had significant improvement in aPCDAI scores, clinical remission rates, albumin, and hematocrit, and 89.5% of patients had no significant adverse events. Similar results were observed among those who required dose adjustment, including 61.1% achieving clinical remission, and among those with perianal disease, including 38.5% achieving clinical remission. CONCLUSIONS: Our data suggest that, within our cohort of pediatric patients with CD, UST has long-term efficacy with no observed safety concerns. Dose adjustment may be helpful in achieving clinical remission.

Depression Predicts Prolonged Length of Hospital Stay in Pediatric Inflammatory Bowel Disease.

OBJECTIVE: Few studies report the impact of depression on inflammatory bowel disease (IBD)-related hospitalizations. We evaluated the association between depression and pediatric IBD-related hospitalizations. Our primary aim was to test the hypothesis that depression is associated with hospital length of stay (LOS); our secondary goal was to evaluate if patients with depression are at higher risk for undergoing additional imaging and procedures. METHODS: Data were extracted from the 2012 Kids Inpatient Database (KID), the largest nationally representative publicly available all-payer pediatric inpatient cross-sectional database in the United States. Hospitalizations for patients less than 21 years with a primary diagnosis Crohn disease (CD) or ulcerative colitis (UC) by ICD-9 code were included. Multivariable logistic regression was used to predict long LOS controlling for patient- and hospital-level variables and for potential disease confounders. RESULTS: For primary IBD-related hospitalizations (N = 8222), depression was associated with prolonged LOS (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.19-1.90) and total parenteral nutrition use (OR 1.54; 95% CI 1.04-2.27). Depression was not associated with increased likelihood of surgery (OR 0.97; 95% CI 0.72-1.30), endoscopy (OR 0.91; 95% CI 0.74-1.14), blood transfusion (OR 0.85; 95% CI 0.58-1.23), or abdominal imaging (OR 1.15; 95% CI 0.53-2.53). CONCLUSIONS: Depression is associated with prolonged LOS in pediatric patients with IBD, even when controlling for gastrointestinal disease severity. Future research evaluating the efficacy of standardized depression screening and early intervention may be beneficial to improving inpatient outcomes in this population.