Pediatric Drugs最新文献

{"title":"Extrapolating Guselkumab Efficacy to Juvenile Psoriatic Arthritis from Adult Psoriatic Arthritis and Adult and Pediatric Psoriasis Data.","authors":"Herta Crauwels, Sarah Ringold, Samantha Howard, Bart Van Hartingsveldt, Valerie Smith, Meg Jett, Tristan Baguet, Elizabeth Adamson, Soumya D Chakravarty, Jocelyn H Leu","doi":"10.1007/s40272-025-00725-2","DOIUrl":"10.1007/s40272-025-00725-2","url":null,"abstract":"<p><strong>Background: </strong>Psoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar features that differ by age and sequence of symptom onset. PsA and psoriasis (PsO) share comparable pathology across ages, with interleukin (IL)-23 as a key mediator. Prior to the recent US FDA approval of guselkumab for treatment of pediatric plaque PsO and active jPsA, no approved pediatric treatment selectively targeted IL-23 signaling. Guselkumab (a fully human, dual-acting, IL-23p19 subunit inhibitor) was shown to be safe and effective in adult PsO and PsA, with consistent clinical benefits and safety in pediatric PsO. As jPsA shares features, including clinical characteristics and pathogenesis, with PsO and PsA, findings were extrapolated to jPsA using a similar approach previously applied to support ustekinumab and golimumab use in jPsA, which served as precedents for these analyses with guselkumab.</p><p><strong>Aims: </strong>The aim of this study was to demonstrate the similarity of serum guselkumab concentrations, clinical response, and safety among children and adults with PsO and/or PsA in guselkumab randomized controlled trials.</p><p><strong>Methods: </strong>One-year data from participants receiving guselkumab at Week (W)0, W4, then every 8 weeks in VOYAGE 1/2 (adult PsO; N = 1221), DISCOVER-1/-2 (adult PsA; N = 375), and PROTOSTAR (pediatric PsO; N = 92; n = 3 with concurrent jPsA) were included. Serum guselkumab concentrations, Investigator Global Assessment of clear/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 75/90/100 response rates and safety outcomes were summarized.</p><p><strong>Results: </strong>Serum guselkumab concentrations over 1 year were similar between pediatric (max median: 3.2 µg/mL) and adult PsO (3.7 µg/mL), adult PsO and PsA (4.2 µg/mL), and pediatric PsO and adult PsA. IGA 0/1 response rates at W16 were approximately similar in guselkumab-treated participants with pediatric PsO (66%), adult PsO (84%), and adult PsA (77%). W16 PASI 75/90/100 response rates were comparable across guselkumab-treated participants with pediatric PsO without jPsA (PASI 75: 77%; PASI 90: 56%; PASI 100: 33%), pediatric PsO with jPsA (1 of 2 participants achieved all PASI improvement levels), and adult PsA (77%; 55%; 22%). Guselkumab safety outcomes were similar across ages and diseases.</p><p><strong>Conclusion: </strong>Comparable pharmacokinetic and clinical findings with guselkumab in children with PsO (3 with concurrent jPsA) and adults with PsO and PsA support the extrapolation of efficacy and safety data from adults to children with jPsA, supporting guselkumab use in jPsA.</p><p><strong>Clinical trials registration: </strong>The clinical trials included in this analysis are registered at www.</p><p><strong>Clinicaltrials: </strong>gov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"69-81"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12864257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Pharmacotherapy for Congenital Hyperinsulinism.","authors":"Nuria González-Llorens, Daphne Yau, María Clemente León, Huseyin Demirbilek, Indraneel Banerjee, Pratik Shah","doi":"10.1007/s40272-025-00727-0","DOIUrl":"10.1007/s40272-025-00727-0","url":null,"abstract":"<p><p>Congenital hyperinsulinism (CHI) is a rare disorder causing persistent hypoglycaemia in infants due to excessive insulin secretion from pancreatic β-cells. It has genetic causes, primarily mutations in ATP-sensitive potassium channel genes (ABCC8, KCNJ11). CHI manifests in three forms-focal, diffuse, and atypical-distinguished by histology and genetics, influencing treatment strategies. Early diagnosis and tailored management are vital to prevent neurological damage. While transient CHI resolves spontaneously, permanent CHI often requires complex medical and/or surgical intervention. Despite advances, long-term neurodisability remains high, highlighting increased need to improve monitoring as well as better therapies with lesser side effects. Acute treatment aims to rapidly normalize glucose levels and long-term treatments include diazoxide (KATP channel agonist) to suppress insulin secretion, though its effectiveness depends on genetic mutation type. Other therapies include somatostatin analogues. Newer emerging therapies include novel glucagon analogues, monoclonal antibodies targeting insulin receptors, GLP-1 receptor antagonist, and selective somatostatin receptor agonist, currently under clinical trials. Along with medical treatment, children may require additional feeding support with carbohydrate supplementation using glucose polymers and special formulas. Continuous glucose monitoring aids detection but has limitations. Surgery is preferred for focal lesions to potentially cure CHI.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"15-29"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medulloblastoma: Current Standard of Care and Future Treatment Opportunities.","authors":"Lisa Mayr, Amedeo A Azizi, Johannes Gojo, Andreas Peyrl","doi":"10.1007/s40272-025-00726-1","DOIUrl":"10.1007/s40272-025-00726-1","url":null,"abstract":"<p><p>Medulloblastoma, the most common malignant brain tumor of childhood, is an aggressive embryonal tumor that arises from the posterior fossa. On the molecular level, four clinically relevant subgroups have been established, which have already been integrated into routine diagnostic procedures and treatment stratification. The initial step in treating medulloblastoma typically involves maximal safe surgical resection, followed by craniospinal irradiation in most patients (except very young children) and chemotherapy. Efforts to improve cure rates and reduce long-term detrimental effects led to the reduction in radiotherapy and adaptation of chemotherapy. Gradually, over the past decades, these strategies have resulted in significant improvements in treatment outcomes. However, patients with a medulloblastoma recurrence still fare badly, especially those children who already had radiotherapy as part of their initial treatment. Whereas there is no universal treatment strategy at relapse and the outcome remains poor, recently, the administration of anti-angiogenic metronomic therapy led to sustained long-term survival in a quarter of patients. Nonetheless, there remains an unmet need to improve survival and mitigate therapy-induced morbidity by developing new treatment strategies. Promising new approaches include targeting the Sonic Hedgehog pathway, addressing transcriptional and epigenetic drivers, improving drug delivery, and overcoming treatment resistance. Although the most common malignant brain tumor of childhood, the number of novel approaches in addition to a molecularly subdivided entity renders it difficult to form large clinical trials.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"31-42"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12864240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosing and Discontinuation of Methylphenidate Medication in Relation to Weight Status in Children and Adolescents.","authors":"Julia Izsak, Elin E Kimland, Jari Martikainen, Elin Dahlén, Linda Halldner, Jenny M Kindblom","doi":"10.1007/s40272-025-00728-z","DOIUrl":"10.1007/s40272-025-00728-z","url":null,"abstract":"<p><strong>Background and objective: </strong>Evidence and clinical guidelines on methylphenidate dosing in different weight status groups are limited. This study aimed to evaluate real-world methylphenidate dosing practices and treatment discontinuation rates in children and adolescents in relation to weight status.</p><p><strong>Method: </strong>We used data from the BMI Epidemiology Study Gothenburg cohort, which includes weight and height measurements linked to national registers. Exposures included body weight, standardised body mass index (zBMI), and body mass index (BMI) status. The main outcome was the dose and weight-adjusted dose of methylphenidate for the baseline and follow-up prescriptions. We used a logistic regression model to evaluate treatment discontinuation in relation to weight status, sex, and age.</p><p><strong>Results: </strong>The study included 1741 children and adolescents who initiated methylphenidate treatment and had BMI available. Among them, 612 had a follow-up prescription with BMI available. Children and adolescents with overweight and obesity received slightly higher absolute doses of methylphenidate at baseline prescriptions, but lower weight-adjusted doses. Children and adolescents with underweight received higher weight-adjusted doses. Absolute dose increases between treatment initiation and follow-up were highest in children and adolescents with obesity and lowest in children and adolescents with underweight. Girls received higher absolute and weight-adjusted doses than boys at follow-up, while children over 12 years of age received higher absolute but lower weight-adjusted doses than children under 12 years. A significantly higher proportion of children and adolescents with baseline underweight discontinued treatment during the first year, compared with the normal weight group. Beside lower baseline zBMI, female sex and higher age were also significantly associated with treatment discontinuation during the first year.</p><p><strong>Conclusion: </strong>Our findings suggest that weight status, sex, and age are significantly associated with differential methylphenidate dosing and treatment discontinuation in children and adolescents.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"89-100"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12864339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Advances in Pharmacotherapy for Congenital Hyperinsulinism.","authors":"Nuria González-Llorens, Daphne Yau, María Clemente León, Huseyin Demirbilek, Indraneel Banerjee, Pratik Shah","doi":"10.1007/s40272-025-00729-y","DOIUrl":"10.1007/s40272-025-00729-y","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"101"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescents' and Young Adults' Adherence to Medication During the Transition to Adult Healthcare: A Developmentally Appropriate Framework for Optimising Adherence-Promoting Interventions.","authors":"Albert Farre, Lauren Huckerby, Nicola J Gray, Roberta Fulton, Janet E McDonagh","doi":"10.1007/s40272-025-00724-3","DOIUrl":"10.1007/s40272-025-00724-3","url":null,"abstract":"<p><p>For adolescents and young adults (AYA) with any health condition, it is important that they learn to manage their condition and healthcare as they transition into adulthood. For AYA with childhood-onset long-term conditions, this is also fundamental for a successful transition from child- to adult-centred services, as this period is associated with a decline in important health behaviours, such as medication adherence, which in turn are associated with poorer clinical outcomes and increased mortality. Current evidence suggests that, even though AYA are at higher risk for non-adherence than other age groups, existing interventions are less likely to be effective, or may bring about more modest benefits, for AYA compared with younger children and older adults. There is still a need for novel, innovative approaches to medication adherence that can help better meet the unique needs of AYA groups. We suggest that developmentally informed and developmentally tailored approaches may offer a promising avenue to achieve this. The most widely reported AYA adherence issues are deeply intertwined with the different stages of AYA biopsychosocial development and, therefore, AYA development can be understood as a common thread underlying AYA adherence issues. Ensuring that AYA adherence-promoting interventions are relative to an ongoing developmental assessment is crucial, not only to better meet AYA needs as they gradually prepare for their transfer to adult care, but also to continue to do so in the often forgotten third phase of transitional care (i.e. following transfer) well into their late adolescence and young adulthood.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"5-13"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40272-025-00732-3","DOIUrl":"https://doi.org/10.1007/s40272-025-00732-3","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antipsychotic Medications for Delirium Treatment in the Pediatric Intensive Care Unit: A Systematic Review.","authors":"Francesca Cavagnero, Annalisa Salerno, Chiara Marchegiani Rizzolli, Luca Marchetto, Valentina Stritoni, Alvise Tosoni, Anna Tessari, Angela Amigoni, Marco Daverio","doi":"10.1007/s40272-025-00716-3","DOIUrl":"10.1007/s40272-025-00716-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Pediatric delirium (PD) is a common but underdiagnosed condition in pediatric intensive care units (PICUs), affecting 17-66% of patients. It is associated with prolonged ventilation and hospitalization, increased healthcare costs, and mortality. While nonpharmacological approaches are considered first-line treatments, pharmacological interventions are used in refractory cases despite limited pediatric-specific evidence. The objective of this systematic review was to evaluate the efficacy and safety of pharmacological treatments for PD in PICUs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42024504618), PubMed, Embase, Scopus, CINAHL, Cochrane, and Web of Science databases were searched for studies published up to February 2024. Eligible studies included children aged 1 month-18 years, diagnosed with PD in the PICU using validated scales or psychiatric evaluation and receiving pharmacologic treatment. Outcomes included delirium improvement or resolution and safety. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) scale.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 7,309 records, 10 studies involving 283 patients receiving pharmacological treatment met inclusion criteria. All but one of the studies were retrospective and no randomized controlled trials (RCTs) were identified. Pharmacological treatment was administered to 283 patients, with the most used agents being quetiapine (36%), risperidone (20%), haloperidol (20%), and olanzapine (11%). Seven studies reported variable efficacy, with olanzapine showing significant symptom improvement in one study (olanzapine: N = 31; control: N = 28; F(1,20) = 28.62, r = 0.77, 95% confidence interval [CI] = 0.50-0.90) and the other drugs reporting a trend toward improvement in delirium severity. Adverse events were inconsistently measured and reported throughout studies: 22 cases were reported, with QTc prolongation (11 cases) and dystonia (7 cases) being the most frequent. Dystonia was observed in patients receiving haloperidol, whereas QTc prolongation was reported in those treated with quetiapine or risperidone. Complete resolution of the events was reported in 21/22 cases and occurred after dose adjustment or treatment interruption.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Pharmacological interventions for PD in PICU patients showed variable efficacy, and adverse events were reported in a minority of treated patients. The limited sample size, the only modest quality of the studies, and the lack of replication preclude definitive conclusions about the drugs' efficacy. In addition, haloperidol, risperidone, and quetiapine raised some safety concerns. Further research is needed to establish stronger evidence for the pharmacologic treatment of PD in the PICU and to addres","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"707-722"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Big Data in the Assessment of Medication Safety in Pregnancy: Opportunities and Challenges.","authors":"Per Damkier, Krista F Huybrechts, Hedvig Nordeng","doi":"10.1007/s40272-025-00718-1","DOIUrl":"10.1007/s40272-025-00718-1","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"673-677"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety of Anti-Interleukin-1 Medications in Children with Rheumatic Diseases: a Systematic Review.","authors":"M Isa, G M Tiller, D F L Liew, W D Renton","doi":"10.1007/s40272-025-00712-7","DOIUrl":"10.1007/s40272-025-00712-7","url":null,"abstract":"<p><strong>Background: </strong>Anti-interleukin-1 (IL-1) biologic disease-modifying anti-rheumatic drugs are the mainstay for several childhood rheumatic and autoinflammatory diseases. Long-term medication safety is a key consideration for chronic disease management.</p><p><strong>Aim: </strong>The objective was to synthesise evidence on the long-term safety of anti-IL-1 medications in children and young people with rheumatic diseases, including autoinflammatory diseases.</p><p><strong>Methods: </strong>The study protocol was registered prospectively (PROSPERO CRD420251000272). Original full text studies of at least ten patients presenting safety data on anti-IL-1 medications in children with rheumatic diseases were eligible for inclusion. Medline, Embase and Web of Science were searched from inception to 27 February 2025. The methodological index for non-randomized studies (MINORS) tool was used to assess risk of bias. All relevant safety outcomes were presented and synthesised. Meta-analysis was not performed owing to study heterogeneity.</p><p><strong>Results: </strong>A total of 1660 unique records were screened, and 57 unique studies (3690 patients) were included. In total, 31 were retrospective cohort studies, and 10 were prospective interventional trials. Most studies were of moderate (n = 31) or high (n = 25) risk of bias. Rates of adverse events varied significantly between studies. Injection site reactions (particularly with anakinra) and minor infections were common. Infections were the most common type of serious adverse event. Drug reaction with eosinophilia and systemic symptoms (n = 3) and interstitial lung disease (including related conditions) (n = 9) were reported in patients with systemic onset juvenile arthritis only. Deaths (n = 16) and malignancies (n = 7) were uncommon, often occurring long after anti-IL-1 medication discontinuation and were often deemed to be unrelated to the anti-IL-1 medication.</p><p><strong>Conclusions: </strong>Our results are consistent with the known safety profile of anti-IL-1 medications and show that they are generally safe for use in the context of childhood rheumatic and autoinflammatory diseases. This review of clinical trial and real-world data will help inform clinical decision-making and family counselling when initiating anti-IL-1 medications in children.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"693-705"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}