Pediatric Drugs最新文献

Fremanezumab (fremanezumab-vfrm; AJOVY^®) is a humanized monoclonal antibody developed by Teva Pharmaceuticals to selectively target calcitonin gene-related peptide (a vasodilatory neuropeptide involved in the pathophysiology of migraine). Fremanezumab was first approved in September 2018 in the USA for the prevention of migraine in adults. In August 2025, it was approved in the USA for the preventive treatment of episodic migraine in pediatric patients aged 6-17 years who weigh 45 kg or more. This article summarizes the milestones in the development of fremanezumab leading to this pediatric first approval for migraine.

Background: Pediatric-onset inflammatory bowel diseases (IBD) are associated with an elevated risk of venous thromboembolism (VTE). However, data on the VTE risk in these patients treated with novel biologics, particularly vedolizumab, remain limited.

Aims: To evaluate the association between vedolizumab and the risk of VTE compared with other biologics in patients with pediatric-onset Crohn's disease (CD) or ulcerative colitis (UC).

Methods: We emulated a target trial using electronic health records from the TriNetX research network. The study included patients with CD or UC diagnosed before the age of 18 years who were treated with vedolizumab, ustekinumab, or anti-tumor necrosis factor (TNF) agents. Comparative groups were generated using 1:1 propensity-score matching based on relevant confounders. The primary outcome was the occurrence of any VTE within 12 months of follow-up. Cox proportional hazards models were used to compare the risk of VTE between vedolizumab-treated patients and those treated with anti-TNF agents and ustekinumab.

Results: A total of 1806 matched patient pairs were analyzed across four comparisons: patients treated with vedolizumab versus anti-TNF agents (CD = 407 pairs; UC = 443 pairs), and vedolizumab versus ustekinumab (CD = 563 pairs; UC = 393 pairs), respectively. Patients with CD receiving vedolizumab had a significantly higher risk of VTE compared with those receiving anti-TNF therapy (hazard ratio [HR] 8.63; 95% confidence interval [CI] 1.08-69.10; p = 0.014). A higher VTE risk was also observed in vedolizumab-treated patients with CD compared with those treated with ustekinumab (HR 4.64; 95% CI 1.35-15.97; p = 0.007). In contrast, no significant difference in VTE risk was found between vedolizumab and either comparator group in patients with UC.

Conclusions: Treatment with vedolizumab was associated with a higher incidence of VTE than anti-TNF agents or ustekinumab among individuals with CD. Prospective cohort studies are warranted to validate the safety of biologic therapy for pediatric patients with CD.

The urea cycle, a metabolic pathway comprising six enzymes and two transporters, is necessary for mammalian nitrogen detoxification. A deficiency of any of these components disrupts this process, leading to the accumulation of nitrogen in the form of ammonia, which is especially toxic to the brain. For decades, treatment of urea cycle disorders has consisted of nitrogen scavengers, dietary protein restriction, arginine or citrulline supplementation, calorie support, and liver transplant. In 2011, carglumic acid became available as a substitute for N-acetylglutamate for N-acetylglutamate synthase deficiency. The past 10 years, however, have seen the development of enzyme therapy for arginase deficiency and gene therapy for ornithine transcarbamylase deficiency. This article reviews the current status and availability of treatment options for urea cycle disorders.

Biosimilar use for pediatric rheumatologic conditions, such as juvenile idiopathic arthritis (JIA), is increasing owing to the development and release of multiple biosimilars into the US market. The US biosimilar development process of bio-originator and generic medications differs. Bio-originators typically spend the longest amount of time in research and development and require the largest financial investment, followed by biosimilars and, lastly, generic medications. Data available from European countries, where biosimilars have been made available much earlier than in the USA, support the effectiveness and safety of biosimilars in patients with JIA. However, European rheumatology clinicians surveyed highlight continued concerns regarding biosimilar data and experience. Although there are varying perspectives of major stakeholders on biosimilars in the USA-the patients and caregivers, clinicians, manufacturers, and pharmacy benefit managers (PBMs)-the primary goal of all should be patient benefits. These benefits may include improved medication healthcare access overall and during shortage situations or promoting the innovation of biobetters, but biosimilars may conversely negatively impact provider reimbursement, or manufacturers may drive out competition of competing biosimilar manufacturers. There are risks associated with lack of education for medical staff and patients, such as the nocebo effect, and how to reduce those risks is through assisting patients in understanding their new medication and reasons for the change. Credible biosimilar resources may be used to educate medical staff and patients, including the Food and Drug Administration (FDA), American College of Rheumatology (ACR), and Arthritis Foundation. After a patient has been transitioned to a biosimilar, it is necessary to have appropriate medical follow-up and continuous monitoring for efficacy and safety.

Background and objectives: Ustekinumab (USTE) and vedolizumab (VEDO) are increasingly used in paediatric patients with inflammatory bowel diseases (pIBD). However, data on the usefulness of therapeutic drug monitoring (TDM) in children are scarce. The primary objective of this study was to evaluate the association between disease activity, measured by faecal calprotectin (F-CPT), and serum trough levels (TLs) of USTE and VEDO. Secondary outcomes were to explore factors potentially associated with the outcome and exposure, to determine the optimal USTE or VEDO dose that predicts remission (defined as F-CPT < 250 µg/g), to validate our hypothesis using a proof-of-concept cohort (POCC) and to assess the occurrence of serum antibodies to USTE and VEDO.

Methods: This was a prospective single-centre observational study performed at the University Hospital Motol, Prague, Czech Republic. Of the 87 patients (51 Crohn's disease (CD), 30 ulcerative colitis (UC), and 6 IBD unclassified (IBD-U)), drug serum TLs and antibodies were measured in 282 observations (49 treatment courses) of USTE and 359 observations (38 courses) of VEDO. Serum and stool samples were collected before each study drug application during both the induction and maintenance phases of the treatment throughout the entire study period (January 2020 to June 2024). Clinical and laboratory data were obtained from the nationwide prospective registry CREdIT. Patients with perianal disease and those with previous major bowel surgery were not excluded from the study. As a POCC, we analysed a group of pIBD treated at our centre with anti-TNF agents-adalimumab or infliximab.

Results: In a linear multiple regression mixed model, an association was observed between logF-CPT levels and USTE treatment duration (β -0.0010, 95% confidence interval (CI) -0.0015 to -0.0006, p < 0.001) but not with USTE TLs (p = 0.12). VEDO TLs and logF-CPT levels were negatively associated both in the linear (β -0.0173, 95% CI -0.0292 to -0.0053, p = 0.005) and categorical models (p = 0.026), even after adjusting for time. A VEDO TL of 15.1 µg/mL showed the best, though still poor, combination of sensitivity (0.82) and specificity (0.32) to predict F-CPT < 250 µg/g (area under the curve (AUC) 0.56, 95% CI 0.49-0.63). Intensification, induction phase, undetectable TLs, and type of IBD (CD, UC, IBD-U) were not associated with logF-CPT. Slightly elevated anti-drug antibodies were detected in 5 USTE and 16 VEDO observations, with no clinical implications.

Conclusions: TDM of USTE does not appear to be useful in pIBD. TDM of VEDO may assist in therapeutic strategy decisions, although establishing clinically useful cut-offs remains challenging.

Introduction: Congenital capillary-lymphatic-venous malformations (CLVMs) often result in life-threatening complications, which may begin in utero. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been successfully used in children and adults with CLVMs due to its antiproliferative and antiangiogenic properties. However, only two cases of prenatal sirolimus treatment of fetal CLVMs have been published to date, with very limited data on optimal therapeutic scheme and drug dosing.

Case reports: Here we report two cases of effective prenatal and postnatal sirolimus treatment of extensive, complicated fetal CLVMs. The CLVMs were diagnosed prenatally by ultrasound and confirmed by magnetic resonance. The pregnancies were complicated with intralesional bleeding in both cases and polyhydramnios in one. The pregnant women received oral sirolimus from the 32nd and 33rd weeks of gestation to delivery (for 11 and 31 days, respectively). The dose of oral sirolimus for the pregnant women ranged from 2 to 6 mg/day, with a target trough whole-blood level of 7-12 ng/mL, which resulted in the umbilical cord arterial blood levels of 3.8 and 6.4 ng/mL, respectively. Therapeutic effects of prenatal sirolimus were observed in both fetuses: one experienced reduced intralesional bleeding, while the other had a significant decrease in CLVM size. The sirolimus treatment has been continued postnatally in both children, currently aged 20 and 9 months. The mothers and children experienced no adverse events from the treatment.

Conclusions: Administration of sirolimus during pregnancy with maternal blood drug-level monitoring seems to be an efficient and safe treatment option that should be considered in high-risk fetal CLVMs.

Background: Pulmonary hypertension (PH) is a common chronic complication of sickle cell disease (SCD), and patients at risk for PH can be identified by measuring tricuspid regurgitant jet velocity (TRJV). We looked for the possible efficacy of L-arginine for children with SCD who have elevated TRJV.

Methods: In total, 50 children with SCD who had TRJV higher than 2.5 m/s were randomly divided into two groups, each with 25 patients: group 1 (control group) and group 2 (treatment group). Group 2 received L-arginine at a dose of 0.1-0.2 g/kg/day for 3 months. Transthoracic echocardiography was conducted to measure TRJV at baseline and after 3 months, and blood samples were collected at baseline and after 3 months to assess serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactate dehydrogenase (LDH), nitric oxide (NO), L-arginine (LA), asymmetric dimethylarginine (ADMA), and LA/ADMA ratio.

Results: After 3 months of treatment, the L-arginine-treated group had significantly lower TRJV levels than the control group, and compared with baseline. They also had significantly lower NT-proBNP and significantly higher NO, LA and LA/ADMA ratios than the control group and compared with baseline. No significant differences in side effects were observed between the two groups, indicating that L-arginine is safe for these patients.

Conclusions: L-arginine is associated with a reduction in TRJV, NT-proBNP, and improvements in NO biomarkers, suggesting it may be beneficial for reducing the risk of pulmonary hypertension in children with sickle cell disease.

Clinical trial registration: ClinicalTrials.gov identifier NCT05470998.

Although advances in the care of extremely preterm born infants have yielded improvements in survival and reductions in important morbidities, rates of bronchopulmonary dysplasia (BPD) have remained relatively unchanged. As BPD can have a long-lasting impact on the quality of life for survivors of prematurity and their families, this remains a continuing challenge. Treatments that have consistently shown efficacy in preventing either BPD or the composite outcome of BPD and death prior to 36 weeks post menstrual age (PMA) in large-scale randomized clinical trials (RCTs) include caffeine [adjusted odds ratio aOR for BPD, 0.63; 95% confidence interval (95% CI) 0.52-0.76; p < 0.001)], vitamin A [relative risk (RR) for death or BPD 0.89; 95% CI 0.80-0.99], low-dose hydrocortisone in the first week of life [OR for survival without BPD, 1.45; 95% CI 1.11-1.90; p = 0.007], and post-natal dexamethasone [RR for BPD or mortality; 0.76; 95% CI 0.66-0.87]. Although early caffeine therapy is now a widely used strategy to prevent BPD, the potentially severe side effects of post-natal glucocorticoids and the concerns regarding the cost-benefit of vitamin A have led to inconsistent use of these drugs in clinical practice. Inhaled bronchodilators and diuretics provide differing degrees of symptomatic relief for patients according to their phenotypic pattern of lung injury; however, these medications do not prevent BPD. Currently available pharmaceuticals do not sufficiently address the degree of structural immaturity and immune dysregulation that is present in the growing population of survivors born prior to 25 weeks gestational age. In this article, we provide both an evidence-based summary of pharmacological treatments currently available to prevent and manage BPD and a discussion of emerging therapies that could help preserve normal lung development in infants born preterm.