Personalized dosing is particularly important in pediatric patients, as age-related physiological maturation, developmental changes, and patient-specific factors contribute to substantial pharmacokinetic variability. Standard dosing approaches often fail to adequately account for this heterogeneity and may lead to subtherapeutic or supratherapeutic drug concentrations. Model-informed precision dosing (MIPD) addresses these limitations by integrating individual patient data with population pharmacokinetic/pharmacodynamic models to optimize dosing at the individual level more accurately. This review aimed to (1) provide a structured overview of currently available bedside-compatible MIPD software applications for pediatric dosing, (2) systematically summarize published clinical studies evaluating their use in pediatric and neonatal populations, and (3) illustrate practical bedside application through a step-by-step tutorial. We identified MIPD software tools that incorporate Bayesian forecasting and at least one pediatric module through iterative literature searches using terms for MIPD and dosing software, and by developer verification. For eligible platforms, we reviewed PubMed-indexed clinical studies involving pediatric patients, summarizing key aspects including study design, population, drug, clinical decision support-related objectives, and findings. A representative tutorial was developed using NextDose for neonatal vancomycin dosing. We identified 11 available MIPD software platforms, varying in deployment, model libraries, drug coverage, electronic health record integration, and regulatory status (e.g., CE-marked medical devices vs non-regulated clinical decision support). Review of 26 clinical studies enrolling more than 4000 pediatric and neonatal patients demonstrated that MIPD consistently outperformed conventional methods in predictive accuracy, precision, and pharmacokinetic target attainment, including significant improvements in target area under the curve attainment for key drugs like vancomycin. Benefits included a reduced sampling burden and faster therapeutic exposure, predominantly for antibiotics (vancomycin, tobramycin, gentamicin) and select chemotherapeutics (busulfan). Model-informed precision dosing software tools offer substantial potential to improve precision dosing in pediatrics, with robust evidence of superior target attainment and operational advantages. Gaps remain in prospective randomized trials, direct patient-centered outcome data, cost-effectiveness analyses, non-antibiotic drug coverage, and clinician training.
Despite considerable advancements in the therapeutic landscape of inflammatory bowel disease (IBD) for adults, long delays exist for paediatric IBD (pIBD) approval, with a median delay of >7 years following adult approval. Our aim is to summarise the landscape of pIBD clinical trials through a review of trial registries. We conducted a cross-sectional review of ClinicalTrials.gov and ClinicalTrialsRegister.eu to identify investigational and approved therapeutic agents for the treatment of pIBD. All interventional studies involving pIBD (aged <18 years) from database inception to July 2, 2026, were considered for inclusion. Of 3941 records screened, 123 completed trials (77 randomised controlled trials [RCTs] and 46 non-RCTs) and 90 active trials (55 RCTs and 35 non-RCTs) met the inclusion criteria. A majority of completed trials (71
Ocrelizumab, a recombinant humanized IgG1 monoclonal antibody directed against CD20-expressing B-cells, has been developed by Genentech, Inc. for the treatment of multiple sclerosis (MS). Both intravenous infusion and subcutaneous injection formulations of ocrelizumab are approved in the EU and the USA for the treatment of adults with relapsing or primary progressive forms of MS. In May 2026, the intravenous infusion formulation of ocrelizumab (OCREVUS®) was approved in the USA for the treatment of relapsing-remitting MS (RRMS) in pediatric patients 10 years of age and older who weigh 25 kg or more. This article summarizes the milestones in the development of ocrelizumab leading to this first pediatric approval for RRMS.
Survival for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) exceeds 90
This phase 3, multicenter, randomized, open-label study (NCT05126901) compared oral ferric maltol with ferrous sulfate, across 23 sites in the US and the UK, evaluating the safety, efficacy, pharmacokinetics, tolerability, and palatability of age-specific doses in infants, children and, adolescents with iron deficiency anemia (IDA). In a 12-week study, a total of 61 children/adolescents aged 2–17 years (median age 14 years; 45 female patients [73.8
The management of migraine during pregnancy and lactation poses a major challenge owing to the paucity of safety data. While very little safety data are available for new targeted migraine therapies such as calcitonin gene receptor protein (CGRP) blocking medications, including the CGRP monoclonal antibodies and gepants, well-established migraine therapies such as topiramate, valproate, and dihydroergotamine have known risk for teratogenicity. Likewise, the safety evidence for commonly used therapies for migraine in pregnancy such as propranolol and verapamil is of low quality, and the level of evidence for efficacy of verapamil is limited. Meanwhile women experience migraine at the highest rates during their reproductive years necessitating an effective and balanced approach that considers maternal and fetal risk as well as optimal benefit to the patient to ensure adequate and appropriate treatment during pregnancy and lactation. The purpose of this review is to provide an overview of the available data on the safety of available and efficacious medications in the management of migraine during pregnancy and lactation. Based on more recent studies, there is increased evidence for use of more specific and efficacious medications for migraine, such as onabotulinumtoxinA, local nerve blocks with lidocaine, and triptans during pregnancy and lactation.
Severe forms of alopecia areata (AA) often require off-label systemic treatments (ST) for which data on effectiveness and safety are limited. This study aimed to provide a comprehensive real-world overview of ST patterns in children with severe AA. We conducted a retrospective, longitudinal, multicenter study of children with AA (aged <18 years) receiving at least one ST (2010–2023), identified using a keyword search in Ouest Data Hub Warehouse (a hospital data network in France with a critical mass of 5.1 million patients) or by members of the Société Française de Dermatologie Pédiatrique. The primary outcome was drug survival (DS), defined as time on ST, and the secondary outcomes included reasons for treatment discontinuation and long-term observations. Among the 262 included children (median age at AA onset: 9 years; 58.4 Alopecia areata is a common chronic disease causing hair loss. Severe forms often require systemic treatments, for which data concerning efficacy and safety are limited. This study aimed to provide an overview of systemic treatment patterns in children with severe alopecia areata in France. We conducted a retrospective study using medical records from west regional French hospitals or obtained by members of the Société Française de Dermatologie Pédiatrique. We analyzed how long treatments were continued and the reasons why they were discontinued. A total of 262 children (58.4
A recent consensus report defined anaphylaxis as a serious allergic reaction that may involve the skin/mucosa, respiratory, cardiovascular, and/or gastrointestinal systems that can progress rapidly and may cause death. Epinephrine treatment is recommended in suspected anaphylaxis cases; however, numerous barriers exist to consistent, widespread epinephrine use, including difficulty identifying anaphylaxis signs and symptoms; challenges recognizing when to use epinephrine; low propensity of prescribing and filling prescriptions; low epinephrine carrying rates; knowledge gaps in epinephrine administration techniques; fears of contacting emergency medical services; use of antihistamines, inhaled bronchodilators, and other medications as first-line agents over epinephrine; and limited epinephrine device availability in community settings (e.g., schools, daycares, and restaurants). To address these challenges, healthcare providers should provide training and educational resources to caregivers on signs and symptoms of anaphylaxis that warrant epinephrine use, how to use epinephrine devices, and the importance of having epinephrine readily available at all times. System-level strategies, including measures to improve access, legislative efforts to stock epinephrine in childcare centers, and scalable digital education approaches, are also needed. Furthermore, healthcare providers should implement shared decision-making with caregivers to prepare and empower caregivers to make informed decisions when managing anaphylactic events. Understanding barriers to consistent, widespread epinephrine use when infants and toddlers experience anaphylaxis and providing actionable educational tools to caregivers alongside system-level strategies can improve outcomes in this vulnerable population. Anaphylaxis is a serious, possibly fatal event. The rate of anaphylaxis among young children has been increasing in the USA over the past decade. It is important to educate doctors and caregivers on the signs of anaphylaxis and when to give epinephrine to infants and toddlers during an anaphylactic event. Epinephrine is the standard treatment when someone has a possible anaphylactic event, but people can face challenges when giving epinephrine. These challenges include: correctly identifying the signs of anaphylaxis, knowing when to use epinephrine, low rates of prescribing epinephrine and filling those prescriptions, not carrying epinephrine, not knowing how to administer epinephrine, fears about calling emergency medical services, using other medicines instead of epinephrine, and lack of epinephrine availability in public spaces. To address these challenges, doctors should talk with caregivers and make plans together about how to best prepare for any anaphylactic event their infant or toddler could face. Doctors and caregivers can take steps together such as making an Anaphylaxis Action Plan, training with their epinephrine device, and discussing updated expert guidelines and how to implement them. Understanding the challenges that caregivers face when managing anaphylaxis in infants and toddlers can help improve outcomes in this vulnerable population.
Colchicine is the cornerstone of treatment in familial Mediterranean fever and is generally recommended as lifelong therapy. However, a subset of pediatric patients may experience a milder disease course, raising questions about the feasibility and safety of colchicine discontinuation. Evidence guiding this decision remains limited, and no consensus exists on patient selection criteria or monitoring strategies. The objective of this study was to evaluate long-term outcomes after colchicine discontinuation in a large pediatric familial Mediterranean fever cohort and to identify clinical and genetic factors associated with sustained colchicine-free remission. We retrospectively analyzed medical records of 2316 pediatric patients diagnosed with familial Mediterranean fever and followed at the Pediatric Rheumatology Unit of Istanbul University, Istanbul Faculty of Medicine, Istanbul, Türkiye. Patients fulfilling at least one of the Tel-Hashomer or Eurofever/Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria and carrying at least one pathogenic or likely pathogenic MEFV (Mediterranean fever) gene mutation were eligible. Colchicine was discontinued in 127 patients (5.48
Despite major therapeutic advances in recent years, and early signs that the overall standard of care we can deliver to children with inflammatory bowel disease (IBD) is improving, the promise of precision medicine remains largely unfulfilled in daily practice. The goal is to match the right therapy to the right patient, in the right time window, so that treatment intensity reflects true disease biology and future risk rather than broad population averages. However, this approach is still an unmet need. Even when management is framed within a risk-based paradigm, clinical decisions are often guided by generalized recommendations and imperfect predictors, with limited capacity to individualize strategies at diagnosis and during follow-up. As a result, two opposite but equally relevant pitfalls remain very real. On one hand, overtreatment can lead to unnecessary exposure to immunosuppressive regimens in children and adolescents with mild, slowly progressive, or self-limited disease, increasing the burden of adverse events, monitoring, and psychosocial impact. On the other hand, undertreatment in truly high-risk patients can delay effective control of inflammation, allowing ongoing tissue damage, disease extension, growth impairment, and avoidable complications, ultimately worsening long-term outcomes. This critical review summarizes and critically appraises current recommendations and available evidence, focusing on the pitfalls of overtreatment and undertreatment in pediatric IBD.
ImportanceSirolimus is increasingly used for complex vascular and lymphatic anomalies in neonates and infants. While dyslipidemia is a known adverse effect in adults, the incidence, timing, and severity in this population remain poorly characterized.ObjectiveThe aim of this study was to evaluate the reporting odds and characteristics of sirolimus-associated dyslipidemia in neonates and infants compared with older populations.Design, Setting, and ParticipantsThis study combined a single-center retrospective cohort study and global pharmacovigilance analysis. The clinical cohort included neonates and infants treated with sirolimus at Nagoya University Hospital (October 2018-September 2025). The pharmacovigilance analysis utilized VigiBase (up to September 1, 2025) to perform age-stratified disproportionality analyses.Main Outcomes and MeasuresIn the clinical cohort, lipid profiles (total cholesterol, LDL-C, triglycerides) were assessed pre- and post-treatment. In VigiBase, adjusted reporting odds ratios (aRORs) for dyslipidemia and time-to-onset (TTO) were estimated across age groups, adjusting for sex, region, and concomitant medications.ResultsThe cohort included 10 patients (median age, 44.5 days). Post-initiation, 100% developed hypertriglyceridemia and 90% developed hypercholesterolemia. In VigiBase (17,802 sirolimus-related reports), the dyslipidemia reporting signal was highest in infants (28 days-23 months), with an aROR of 147.08 (95% CI 79.67-271.54), substantially exceeding that in adults aged 18-45 years (aROR 2.31; 95% CI 1.75-3.06). Among infant reports with available TTO data, median TTO was 11.0 days (IQR 5.5-15.8), compared with 29.5 days in adults.Conclusions and RelevanceNeonates and infants showed a markedly stronger dyslipidemia reporting signal than older age groups, and lipid abnormalities were common in the clinical cohort. These findings support baseline lipid assessment and early monitoring after sirolimus initiation in very young patients, including within the first two weeks of therapy. The pharmacovigilance findings should be interpreted as hypothesis generating.
Copper histidinate (ZYCUBO®) is a bioavailable copper replacement therapy developed by Cyprium Therapeutics and Sentynl Therapeutics for the treatment of Menkes disease, a genetic disorder caused by variants in the copper transporter gene, ATP7A. Because copper cannot be absorbed from the gastrointestinal tract by individuals with Menkes disease, copper histidinate is administered as a daily subcutaneous injection. In January 2026, copper histidinate received its first approval in the USA by the U.S. Food and Drug Administration for the treatment of Menkes disease in pediatric patients. Orphan Designation was granted by The European Commission to copper histidinate for the treatment of Menkes disease. This article summarizes the milestones in the development of copper histidinate leading to this first approval for Menkes disease in pediatric patients.
Obesity in reproductive-age women is associated with increased risk of cardiometabolic disease, infertility, and pregnancy-related complications affecting both the mother and fetus. Recently, the introduction of highly effective glucagon-like peptide-1 (GLP-1) receptor agonists has led to increased utilization of obesity medications in this population. While these agents are not recommended during pregnancy, their use in the preconception, periconception, and postpartum periods is increasing. Yet, data on their safety and clinical utility during these reproductive windows remain limited. This review summarizes the current literature on the risks and benefits of GLP-1 receptor agonist use for both the mother and fetus, highlighting the need for ongoing high-quality research in this population. This review highlights key clinical considerations across reproductive stages, emphasizes the primacy of human exposure data where available, and identifies critical evidence gaps requiring future prospective study.
Infants and young children with severe atopic dermatitis (AD) have a high burden of disease with a strong impact on quality of life. Here we assess long-term efficacy and safety of dupilumab in pediatric patients aged 6 months to 5 years with severe AD. This is a subgroup analysis of patients aged 6 months to 5 years enrolled in the ongoing LIBERTY AD PED open-label extension (OLE) study of dupilumab who had previously participated in the parent study LIBERTY AD PRESCHOOL part B and had severe AD (Investigator’s Global Assessment [IGA] = 4) at parent study baseline. Patients received weight-tiered dupilumab every 4 weeks (200 mg for patients weighing 5 to < 15 kg; 300 mg for patients weighing 15 to < 30 kg). Key endpoints included the incidence and rate of treatment-emergent adverse events (TEAEs), the proportion of patients with a ≥ 75 Atopic dermatitis (AD) is one of the most common inflammatory diseases in children. Severe AD can have a strong negative impact on children’s well-being, with a high risk of long-term persistence. In a previous study, treatment with dupilumab for 16 weeks demonstrated significant health benefits in children aged 6 months to 5 years with severe AD. To analyze the effects of dupilumab treatment for a longer time, children who had participated in the 16-week study continued in the present study, in which they received 200/300 mg of dupilumab (depending on body weight) every 4 weeks for up to 2 years. During 2 years of treatment, 88
Ferric maltol (ACCRUFeR®), is an oral iron replacement product being developed by Shield Therapeutics plc for the treatment of iron deficiency (ID). Ferric maltol was originally approved for the treatment of iron deficiency anemia (IDA) in adult patients with inflammatory bowel disease in 2016 (with an indication extension for ID/IDA in adults in 2018) in the EU, and in ID in adults in 2019 in the USA. In December 2025 the indication in the USA was extended to include pediatric patients aged ≥ 10 years. A similar indication extension in pediatric patients aged ≥ 12 years is being evaluated in the EU. This article summarizes the milestones in the development of ferric maltol leading to this first pediatric approval for the treatment of ID.
BackgroundCentral precocious puberty is the early onset of puberty due to premature activation of the hypothalamic-pituitary-gonadal axis, which can reduce adult height. Leuprolide, a gonadotropin-releasing hormone agonist, reduces gonadotropin secretion and is the standard treatment for central precocious puberty.ObjectiveThis study aimed to build a population model to describe the pharmacokinetics of a 3-month leuprolide acetate depot formulation in pediatric patients with central precocious puberty, evaluate covariate effects (age and weight) on leuprolide pharmacokinetics, and assess flat-dosing feasibility in pediatrics.MethodsSamples from 48 patients (aged 1-10 years) were collected over 24 weeks following the administration of 11.25 and 30 mg of a leuprolide acetate 3-month depot formulation. A population pharmacokinetic model was developed using non-linear mixed-effects modeling (NONMEM). Covariate effects were tested using a forward inclusion and backward elimination approach and exploratory data analysis.ResultsA one-compartment model with immediate and delayed first-order absorption and proportional error model best described leuprolide pharmacokinetics in children. A transit compartment model characterized the delayed absorption. Apparent clearance and volume estimates were 181 L/day and 7.11 L, respectively, which were in alignment with those estimated in adult patients with prostate cancer. The immediate and delayed absorption rate constants were 0.441 day-1 and 0.00879 day-1, respectively. The number of transit compartments and the mean transit time were 3 and 34.1 days, respectively. No covariates significantly affected leuprolide pharmacokinetics.ConclusionsThe developed model adequately characterized leuprolide pharmacokinetics in pediatrics. No significant covariate effects were observed, supporting the use of a fixed leuprolide dose in pediatrics.Clinical Trial RegistrationNCT00635817, registered 13 March, 2008.
Lactoferrin is an iron-binding glycoprotein existing in mammalian milk. It has immunomodulatory, antioxidant, and anti-inflammatory properties, and it can also regulate metabolism. The present study investigated the effect of lactoferrin in obese children and adolescents with metabolic dysfunction-associated steatotic liver disease. This randomized controlled trial was performed on 73 obese children and adolescents with metabolic dysfunction-associated steatotic liver disease. The patients were randomized into two groups: group I, who received lactoferrin 100 mg once daily for 3 months, and group II, who did not receive lactoferrin or placebo as the control group. Both groups were on a hypocaloric diet. Measurements of weight, body mass index, alanine aminotransferase, aspartate aminotransferase, fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance, lipid profile, homocysteine, malondialdehyde, interleukin-6, and interleukin-10 were assessed at baseline and after 3 months of treatment. Seventy patients completed the study. After 3 months of treatment, the lactoferrin group had a significantly lower weight, body mass index (28.7 ± 1.48 vs 30.2 ± 1.45, p < 0.001), alanine aminotransferase (47.7 ± 4.4 vs 56.4 ± 4.3, p < 0.001), homeostatic model assessment method of insulin resistance (2.86 ± 0.43 vs 3.08 ± 0.4, p = 0.03), aspartate aminotransferase, fasting blood glucose, total cholesterol, triglycerides, homocysteine, malondialdehyde, and interleukin-6 compared with the control group and the pre-treatment levels. Lactoferrin may help in weight reduction, improve insulin resistance and lipid profile, and decrease oxidative stress and inflammation in obese children and adolescents with metabolic dysfunction-associated steatotic liver disease. The clinical trial was registered at Pan African Clinical Trial Registry with ID: PACTR202302847529384,T https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24309 .
Despite considerable progress in preventing mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), eliminating paediatric HIV has not been achieved. Extended postnatal prophylaxis (ePNP), defined as prophylaxis administered to an HIV-exposed child after PMTCT perinatal prophylaxis ends, has been evaluated and is now proposed as an improved approach towards elimination. This approach should be urgently incorporated into international PMTCT recommendations. The antiretroviral drugs most commonly studied as ePNP, either alone or in combination, are lamivudine, nevirapine, lopinavir/ritonavir and zidovudine. In this study, we examined the efficacy, safety, pharmacology, genetic barrier to resistance and practicality of various ePNP regimens. Regimens combining multiple antiretroviral drugs are no more effective than single-drug regimens in terms of protective efficacy but they are associated with increased toxicity. On the basis of these criteria, we recommend lamivudine as the preferred ePNP drug or nevirapine as an alternative. Guided by maternal HIV viral load, ePNP may be particularly indicated, as it could ensure that the prophylaxis provides the greatest benefit/risk to children at highest risk. Long-acting injectable antiretroviral drugs and broadly neutralising antibodies (bNAbs) have yet to be fully evaluated in neonates, infants and children; however, they may offer new alternatives in the future.
