Ustekinumab for anti-tumor necrosis factor refractory pediatric ulcerative colitis: a promising approach towards endoscopic healing.

BACKGROUND/AIMS: To describe the role of ustekinumab in inducing remission and endoscopic healing in anti-tumor necrosis factor α nonresponsive pediatric ulcerative colitis patients at a tertiary care inflammatory bowel disease center. METHODS: A retrospective chart review was performed on patients with ulcerative colitis receiving ustekinumab. Primary outcome was steroidfree clinical remission at follow-up. Secondary outcomes were biochemical remission and endoscopic healing. RESULTS: Ten children were analyzed; 7 (70%) had ulcerative colitis, and 3 (30%) had inflammatory bowel disease unspecified with colitis. Median follow-up period was 56 weeks. Nine patients (90%) achieved steroid-free clinical remission and biochemical remission. Seven patients had follow-up colonoscopies, out of which 6 (86%) achieved endoscopic remission, while 1 (14%) underwent colectomy. Out of the 3 patients without a follow-up colonoscopy, fecal calprotectin levels downtrended to < 150 mg/kg in 2 patients and < 400 mg/kg in 1 patient from baseline level of > 2,000 mg/kg. CONCLUSIONS: Ustekinumab appears efficacious in achieving not only clinical and biochemical remission but also has promising role in inducing endoscopic healing end point in patients who fail other biologics.

Safety and Durability of Accelerated Infliximab Dosing Strategies in Pediatric IBD: A Single Center, Retrospective Study.

OBJECTIVES: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD. METHODS: We performed a retrospective single-center study of pediatric IBD patients started on IFX over a 10-year period. RESULTS: Two hundred ninety-one patients were included (mean age = 12.61, 38% female) with a follow-up range of 0.1-9.7 years from IFX induction. One hundred fifty-five (53%) were started at a dose of 10 mg/kg. Only 35 patients (12%) discontinued IFX. The median duration of treatment was 2.9 years. Patients with ulcerative colitis ( P ≤ 0.01) and patients with extensive disease ( P = 0.01) had lower durability, despite a higher starting dose of IFX ( P = 0.03). Adverse events (AEs) were observed to occur at a rate of 234 per 1000 patient-years. Patients with a higher serum IFX trough level (≥20 µg/mL) had a higher rate of AEs ( P = 0.01). Use of combination therapy had no impact on risk of AEs ( P = 0.78). CONCLUSIONS: We observed an excellent IFX treatment durability, with only 12% of patients discontinuing therapy over the observed timeframe. The overall rate of AEs was low, the majority being infusion reactions and dermatologic conditions. Higher IFX dose and serum trough level> 20 µg/mL were associated with higher risk of AEs, the majority being mild and not resulting in cessation of therapy.

Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice.

Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight was markedly increased; using the flexiVent small animal ventilator (SCIREQ, Inc.), we find inspiratory capacity, elastance and hysterisivity to be increased while resistance was not changed. Cholesterol measurements show a doubling of lung cholesterol levels. Collagen is also increased. Treatment of Npc1(-/-) mice with hydroxypropyl-ß-cyclodextrin (HPBCD), despite efficacious effects in brain and liver, results in little difference from age-matched controls (using a CNS-expressed transgene to extend the life expectancy of the Npc1(-/-) mice) for these variables.