Tofacitinib Therapy in Children and Young Adults With Pediatric-onset Medically Refractory Inflammatory Bowel Disease.

OBJECTIVES: Tofacitinib, a selective Janus kinase inhibitor, effectively induces and maintains remission in adults with inflammatory bowel disease (IBD), but data are limited in children. This study aimed to evaluate the efficacy and safety of tofacitinib for medically refractory pediatric-onset IBD. METHODS: This single-center retrospective study included subjects ages 21 years and younger who started tofacitinib for medically refractory IBD. Clinical activity indices, clinical response, steroid-free remission, biochemical response, and adverse events (AEs) were evaluated over 52 weeks. RESULTS: Twenty-one subjects, 18 with ulcerative colitis or indeterminate IBD, received tofacitinib. At the end of the 12-week induction period, 9 out of 21 (42.9%) subjects showed clinical response and 7 out of 21 (33.3%) were in steroid-free remission. Of evaluable subjects at 52 weeks, 7 out of 17 (41.2%) showed clinical response and were in steroid-free remission. Of those remaining on tofacitinib at 1 year, none required concomitant systemic corticosteroids. Tofacitinib was discontinued in 8 subjects because of refractory disease, including 8 who ultimately underwent colectomy, and in 1 subject who developed a sterile intra-abdominal abscess. There were no instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia, all of which were AEs of interest. CONCLUSIONS: There is limited experience with tofacitinib in pediatric IBD. In this cohort, tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. This study provides encouraging evidence for the efficacy and safety of tofacitinib as part of the treatment paradigm for young individuals with moderate-to-severe IBD. Larger, well-powered, prospective studies are warranted.

Comorbid Diagnosis of Eosinophilic Esophagitis and Inflammatory Bowel Disease in the Pediatric Population.

BACKGROUND AND AIMS: The incidence and prevalence of eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are rising with similar patterns. Co-occurrence of both diseases in the same patient has been increasingly reported. We sought to examine the pediatric population with both EoE and IBD to better understand the epidemiology and clinical implications of this overlap. METHODS: We conducted a retrospective case-control study at 2 tertiary care children's hospitals. Subjects with both EoE and IBD were identified and compared with randomly selected controls with EoE and IBD alone in terms of: demographics, atopic conditions, IBD classification, location and phenotype of Crohn disease (CD), IBD medications, endoscopic findings, and histopathology. Descriptive statistics summarized the data. RESULTS: Sixty-seven subjects with dual-diagnosis were identified across both institutions. The prevalence of IBD in the EoE population was 2.2% and EoE in IBD was 1.5%. Subjects with both diseases were more likely to have IgE-mediated food allergy compared with IBD alone (36% vs 7%, P < 0.001). Subjects with CD-EoE were less likely to have perianal disease than CD alone (2% vs 20%, P = 0.004). There was no difference in fibrostenotic EoE between the dual-diagnosis group and EoE alone. Treatment with a TNF-alpha inhibitor (anti-TNF) for management of preexisting IBD was protective against development of EoE with a relative risk of 0.314 [95% confidence interval [CI] 0.159-0.619]. CONCLUSIONS: This is a unique population in whom the underlying pathway leading to dual-diagnosis is unclear. Concomitant atopic conditions, especially IgE-mediated food allergy, and medication exposures, particularly anti-TNFs, may help predict likelihood of developing dual-diagnosis.

Post-induction infliximab trough levels and disease activity in the clinical evolution of pediatric ulcerative colitis.

BACKGROUND AND AIMS: Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. METHODS: In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. RESULTS: A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p = 0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission (p = 0.04, p < 0.001, and p = 0.01, respectively). In a multivariate analysis, a PUCAI ≥65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure (p = 0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p = 0.05). Kaplan-Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1-15.6%) in children with severe UC and 3.92% (95% CI 2.9-10.8%) in patients with moderate UC (logrank test p = 0.06). CONCLUSIONS: Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.

Risk factors for recurrent shoulder dystocia, Washington state, 1987-2004.

OBJECTIVE: The objective of the study was to identify recurrent shoulder dystocia risk factors. STUDY DESIGN: This was a population-based case-control study in Washington state (1987-2004). Primary and recurrent shoulder dystocia incidences were calculated. Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for subsequent shoulder dystocia risk factors. RESULTS: Primary and recurrent shoulder dystocia annual incidences were 2.3 of 100 and 13.5 of 100. Of 26,208 women with shoulder dystocia deliveries, 8991 had subsequent vaginal births, and of those, 1060 (11.8%) had a recurrent shoulder dystocia. Index pregnancy birthweight was associated with an increased risk of subsequent shoulder dystocia: 3500-3999 g, aOR 1.8 (95% CI 1.5 to 2.3); 4000-4499 g, aOR 3.3 (95% CI 2.6 to 4.1); 4500-4999 g, aOR 3.1 (95% CI 2.3 to 4.3); and 5000 g or greater, aOR 3.8 (95% CI 2.0 to 7.3). Vacuum delivery, aOR 1.4 (95% CI 1.2 to 1.7), and severe shoulder dystocia, aOR 2.1 (95% CI 1.6 to 2.7) in the index delivery, were also significant. CONCLUSION: Birthweight of 3500 g or greater, vacuum delivery, or severe shoulder dystocia in the index delivery were independent risk factors for shoulder dystocia recurrence.

Home Treatment of Pulmonary Embolism in the Era of Novel Oral Anticoagulants.

BACKGROUND: Outpatient therapy of patients with acute pulmonary embolism has been shown to be safe in carefully selected patients. Problems related to the injection of low-molecular-weight heparin at home can be overcome by use of novel oral anticoagulants. The purpose of this investigation is to assess the prevalence of home treatment in the era of novel oral anticoagulants. METHODS: This was a retrospective cohort study of patients aged ≥18 years with acute pulmonary embolism seen in 5 emergency departments from January 2013 to December 2014. RESULTS: Pulmonary embolism was diagnosed in 983 patients. Among these, 237 were considered ineligible for home treatment because of instability or hypoxia. Home treatment was selected for 13 of 746 (1.7%) patients who were potentially eligible. Anticoagulant treatment for those treated at home was low-molecular-weight heparin or warfarin in 9 (69.2%) and novel oral anticoagulants in 4 (30.8%). Hospitalization was chosen for 733 of 746 (98.3%). Discharge in ≤2 days was in 119 patients (16.2%). Treatment of these patients was low-molecular-weight heparin or warfarin in 76 (63.9%), novel oral anticoagulants in 34 (28.6%), and in 9 (7.6%), anticoagulants were not given because of metastatic cancer or treatment was not known. CONCLUSION: Even in the era of novel oral anticoagulants, the vast majority of patients with acute pulmonary embolism were hospitalized, and only a small proportion were discharged in ≤2 days. Although home treatment has been found to be safe in carefully selected patients, and scoring systems have been derived to identify those at low risk of adverse events, home treatment was infrequently selected.