Characterization of Biologic Discontinuation Among Pediatric Patients with Crohn's Disease.

BACKGROUND & AIMS: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation have not been well-characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD. METHODS: Pediatric patients with CD at 7 U.S. centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease. RESULTS: Of 823 patients included (median age, 13.0 years; 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 µg/mL. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation. CONCLUSIONS: Most children with CD are treated with biologics; 25%-37% discontinue biologics, resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.

A Case of Severe Hepatitis in Infant Twins With COVID-19.

We report a case of nine-month-old twins who presented with bright green diarrhea along with progressively worsening jaundice over one week. On initial evaluation, they were found to have significantly elevated liver enzymes, bilirubin, and alkaline phosphatase levels but without signs of liver failure. They were tested for multiple causes of liver injury including autoimmune and infectious etiologies, which were negative as well. Both twins were incidentally found to be positive for COVID-19 on testing per hospital protocol but did not have any respiratory symptoms. They were monitored closely during their hospital stay and showed clinical stability but with only slight improvement in abnormal lab levels. Ultimately, they were discharged with close outpatient follow-up. They demonstrated full resolution of all lab abnormalities and symptoms two months post discharge.

Yukawa unification predictions with effective "mirage" mediation.

In this Letter we analyze the consequences, for the LHC, of gauge and third family Yukawa coupling unification with a particular set of boundary conditions defined at the grand unified theory (GUT) scale, which we characterize as effective "mirage" mediation. We perform a global χ2 analysis including the observables M(W), M(Z), G(F), α(em)(-1), α(s)(M(Z)), M(t), m(b)(m(b)), M(τ), BR(B→X(s)γ), BR(B(s)→µ(+)µ(-)), and M(h). The fit is performed in the minimal supersymmetric standard model in terms of 10 GUT scale parameters, while tanß and µ are fixed at the weak scale. We find good fits to the low energy data and a supersymmetry spectrum which is dramatically different than previously studied in the context of Yukawa unification.