Pediatric Drugs最新文献

{"title":"Clinical Study to Evaluate the Possible Efficacy and Safety of L-Arginine in Children with Sickle Cell Disease and Increased Tricuspid Regurgitant Jet Velocity: a Randomized Controlled Trial.","authors":"Dalia A Gomaa, Sahar M El-Haggar, Mohamed R El-Shanshory, Osama El-Razaky, Dalia R El-Afify","doi":"10.1007/s40272-025-00701-w","DOIUrl":"10.1007/s40272-025-00701-w","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT05470998.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"605-618"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317615","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":"Comment on \"Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review\".","authors":"Emma Reed, Riya Yadav, Alexandra Mannino, Alessio Provenzani","doi":"10.1007/s40272-025-00703-8","DOIUrl":"10.1007/s40272-025-00703-8","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"663-665"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266999","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":"Levetiracetam Versus Fosphenytoin Infusions as Second-Line Treatment for Pediatric Status Epilepticus: A Multicenter Study Examining Effectiveness, Tolerability, and Ease of Use.","authors":"Armelle Hornard, François Severac, Vincent Laugel, Marie-Thérèse Abi Wardé, Claire Bansept, Yvan de Feraudy, Sandrine Haupt, Marie-Aude Spitz, Didier Eyer, Anne de Saint Martin, Sarah Baer","doi":"10.1007/s40272-025-00709-2","DOIUrl":"10.1007/s40272-025-00709-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Status epilepticus is a life-threatening neurological emergency that requires rapid and effective treatment to prevent long-term complications or death. Traditionally, phenytoin and its prodrug fosphenytoin have been used as second-line therapies following benzodiazepines. However, intravenous levetiracetam has emerged as a promising alternative because of its favorable safety profile and ease of administration, particularly in pediatric populations. This study aimed to evaluate whether intravenous levetiracetam was non-inferior to intravenous fosphenytoin as a second-line treatment for managing pediatric status epilepticus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;From November 2021 to May 2023, we implemented an updated local protocol that replaced fosphenytoin with levetiracetam as the second-line treatment for status epilepticus. Following this change, we conducted a 2-year multicenter study to evaluate its impact. For comparison, we also included patients treated under the previous protocol during the 2 years prior to the change, as a control group. An inverse probability of treatment weighting approach, based on the propensity score, was used to adjust for baseline characteristics between the two groups. Bayesian regression models were used to assess treatment effects in the weighted cohort. Treatment effectiveness was assessed using a composite measure of need for subsequent interventions, recurrence of status epilepticus within 24 h, seizure duration and length of hospital stay. We tested non-inferiority hypotheses for effectiveness criteria and if the probability of non-inferiority was greater than 95%, we also tested a superiority hypothesis. Safety was assessed by analyzing adverse events, mortality, admission to the intensive care unit, and transfer to the resuscitation unit. For safety criteria, only superiority was tested.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 127 patients with status epilepticus were evaluated during the study period; 84 patients in the fosphenytoin group (66%) and 43 patients in the levetiracetam group (34%). Of these, 52 patients had febrile status epilepticus (40.9%), 27 patients were treated with oral levetiracetam as part of their daily treatment regimen at the time of status epilepticus (21.3%), and 12 (9.4%) patients had been treated with levetiracetam during their lifetime but stopped at the time of status epilepticus. With intravenous levetiracetam, 62.8% of children were seizure free, compared with 37.2% of children taking fosphenytoin. The length of hospital stay was significantly shorter with levetiracetam than with fosphenytoin (reduction of 1.9 days with levetiracetam) and children were less likely to be admitted to the intensive care unit (reduction of 18.1% with levetiracetam). The need for third-line treatment or seizure recurrence was significantly lower in the levetiracetam group (16.3% reduction compared with fosphenytoin). Adverse effects and seizure du","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"653-662"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584537","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":"Physiologically Based Pharmacokinetic Modeling-Based Evaluation of Current Carbamazepine and Valproic Acid Dosing Guidelines for Pediatric Epilepsy Treatment.","authors":"Joyce E M van der Heijden, Violette Gijsen, Anne M van Uden, Marika de Hoop-Sommen, Jolien J M Freriksen, Elke Jacobs, Rick Greupink, Saskia N de Wildt","doi":"10.1007/s40272-025-00707-4","DOIUrl":"10.1007/s40272-025-00707-4","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine and valproic acid (VPA) are long-standing treatments for epilepsy in children. Interestingly, they display unique drug disposition characteristics, and maturation of drug metabolizing enzymes further complicates personalized dosing. Physiologically based pharmacokinetic (PBPK) modeling includes these mechanisms so is a promising tool to optimize dosing. Our aim was to better support pediatric drug dosing of carbamazepine and VPA.</p><p><strong>Methods: </strong>All carbamazepine and VPA dosing simulations were conducted with Simcyp, using available carbamazepine and VPA compound models linked with adult and pediatric population models. To verify model adequacy, adult and pediatric pharmacokinetic data were retrieved from the literature to compare predicted carbamazepine and VPA concentrations with observed data. Current Dutch national dosing strategies were then simulated to evaluate their appropriateness to achieve therapeutic levels. Where doses could be optimized, alternative dosing strategies were proposed based on simulations. In addition, the effect of altered albumin levels in children on VPA was explored through simulations under conditions of +20%, average, - 20%, and - 35% age normalized reference albumin levels.</p><p><strong>Results: </strong>Therapeutic levels of carbamazepine and VPA will be reached after 1 or 2 weeks of treatment with the current dosing strategies. Simulations suggest a carbamazepine starting dose of 10 mg/kg/day for neonates rather than 7 mg/kg/day. In addition, children aged 12-18 years may receive a higher starting dose (e.g., 400 mg/day instead of 200 mg/day) to reach therapeutic levels more quickly. For VPA, mean total VPA concentrations dropped below the therapeutic target with reduced albumin levels (i.e., - 20% and - 35%), whereas unbound levels remained within the therapeutic window.</p><p><strong>Conclusion: </strong>Our PBPK simulations support the current pediatric drug dosing recommendations of carbamazepine and VPA. In patients with hypoalbuminemia and when higher VPA doses are needed (i.e., ≥ 30 mg/kg/day), routine determination of unbound VPA concentrations is advised to monitor free VPA concentrations. We demonstrate that PBPK modeling is a valuable tool to confirm and further optimize dosing recommendations in children. PBPK modeling provides valuable comprehensive evidence for guiding clinical practice and potentially informing pediatric drug labeling.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"641-652"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554103","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":"Efficacy and Safety of Wound Catheter Infusion with Ropivacaine After Abdominal Surgery in Children Aged < 1 Year: A Randomized Controlled Trial.","authors":"Lonneke M Staals, Jaap Dogger, Claudia Keyzer-Dekker, Anneke A Boerlage, Eric F Bokhorst, Jan J van Wijk, Jeroen R Scheepe, Monique van Dijk, Joost van Rosmalen, Saskia N de Wildt","doi":"10.1007/s40272-025-00700-x","DOIUrl":"10.1007/s40272-025-00700-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Wound catheter infusion (WCI) with local anesthetics provides effective postoperative analgesia in adults, without adverse effects on wound healing. Studies on WCI in infants are scarce. The aim of this study was to investigate the efficacy and safety of WCI with ropivacaine as treatment for postoperative pain in infants.</p><p><strong>Methods: </strong>We conducted a prospective, randomized, double-blind, placebo-controlled trial including children aged < 1 year undergoing open abdominal surgery. Informed consent was obtained. All children received a wound catheter at the end of surgery and were randomized for treatment with either ropivacaine (bolus dose of 2 mg/kg and continuous infusion of 0.2 mg/kg/h) (R-group) or placebo (C-group), for 72 h postoperatively. The C-group received morphine 100 mcg/kg intravenously at the end of surgery, the R-group received placebo. Standard analgesia postoperatively was paracetamol intravenously and rescue morphine intravenously. Primary outcome was the cumulative amount of morphine (mcg/kg) administered in the first 48 hours postoperatively. Secondary outcomes were the number of patients needing morphine, area under the curve over 24 hours of COMFORT-B and Numeric Rating Scale pain scores, incidence of adverse events, and plasma concentrations of ropivacaine.</p><p><strong>Results: </strong>After inclusion of 30 patients, the study was discontinued because of slow recruitment. In two cases, the wound catheter was accidentally displaced directly after surgery, therefore data of 28 children were analyzed (14 R-group, 14 C-group). Median [interquartile range] cumulative amount of morphine (mcg/kg) administered within 48 hours postoperatively was 0.0 [0.0-642.2] in the R-group, compared with 240.1 [15.1-759.0] in the C-group (P = 0.068). In the R-group, 6/14 children required morphine compared with 13/14 in the C-group (P = 0.013). Pain scores were not significantly different between groups. Plasma concentrations of ropivacaine stayed below toxic thresholds.</p><p><strong>Conclusions: </strong>Cumulative morphine use postoperatively was not significantly different between infants receiving WCI with ropivacaine or placebo, although a lower number in the R-group required morphine. Wound catheter infusion provided adequate analgesia, with no signs of local anesthetic toxicity. The study may have been underpowered because of early discontinuation.</p><p><strong>Clinical trial registration: </strong>The study was registered in EudraCT (2015-002209-12), and the Dutch Trial Registry NTR6130 on 23 November, 2016 (International Clinical Trials Registry Platform NL-OMON20504).</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"593-604"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216551","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":"Authors' Reply to Reed and Colleagues' Comment on \"Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review\".","authors":"Marjan Moghadamnia, Simin Dashti-Khavidaki","doi":"10.1007/s40272-025-00704-7","DOIUrl":"10.1007/s40272-025-00704-7","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"667-669"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266998","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":"A Systematic Review of Anti-TNF and Anti-IL-6 Treatments for Pediatric Takayasu Arteritis: Addressing a Therapeutic Dilemma.","authors":"Ezgi Deniz Batu, Seher Sener","doi":"10.1007/s40272-025-00706-5","DOIUrl":"10.1007/s40272-025-00706-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>Takayasu arteritis (TAK) is a rare large-vessel vasculitis primarily affecting young female patients, with pediatric cases being even rarer. Biologic therapies, such as anti-tumor necrosis factor (anti-TNF) and anti-interleukin-6 (anti-IL-6) agents, have become integral to TAK treatment; however, their use in children is not well supported by robust data due to the rarity of the disease. This systematic review aimed to evaluate the use, effectiveness, and safety of anti-TNF drugs and tocilizumab in the treatment of pediatric TAK.</p><p><strong>Methods: </strong>We conducted a systematic literature search in PubMed/MEDLINE and Scopus databases from their inception until 15 December 2024. Studies were eligible if they included pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs and reported clinical outcomes. Clinical trials, observational studies, case series, and reports were included. Data were extracted independently by two reviewers. Only English articles were analyzed. Due to heterogeneity in study designs and reporting, a narrative synthesis was performed.</p><p><strong>Results: </strong>A total of 94 reports involving 225 pediatric patients with TAK who received 262 treatment courses of biologic treatment were included. Anti-TNF drugs were more frequently used than tocilizumab (74.2% versus 36.9%, p < 0.001). Both groups showed comparable effectiveness, with clinical improvement observed in 64.9% of anti-TNF drug and 70.9% of tocilizumab treatment courses (p = 0.438). The frequency of relapse was also similar between the two groups (~50% in both groups, p = 0.472). Hypertension was more prevalent in the anti-TNF group (p = 0.004), while concurrent glucocorticoid administration was more frequent in the tocilizumab group (p = 0.024). Infliximab was the most frequently used anti-TNF drug, with a higher proportion of patients showing improvement compared with adalimumab (71.1% versus 45.5%). Adverse events were only reported with infliximab (n = 3), including allergic and infusion reactions.</p><p><strong>Limitations: </strong>The evidence is primarily based on case reports and series, which might have introduced selection and publication bias. Additionally, heterogeneity in diagnostic criteria, treatment protocols, and outcome definitions limits the comparability of results across studies.</p><p><strong>Conclusion: </strong>Despite the higher frequency of anti-TNF drug use, both therapies exhibit similar clinical outcomes, highlighting the potential of tocilizumab as an equally effective alternative in pediatric TAK management. Long-term head-to-head studies are needed to optimize the data regarding biologic treatment strategies in pediatric TAK.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"563-574"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326540","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":"Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome in Children-From Pathogenesis to Treatment Strategies: A Comprehensive Review.","authors":"Federica Anselmi, Perrine Dusser, Isabelle Kone-Paut","doi":"10.1007/s40272-025-00699-1","DOIUrl":"10.1007/s40272-025-00699-1","url":null,"abstract":"<p><p>Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent periodic fever syndrome in non-Mediterranean children, usually manifesting before the age of 5 years. It is characterized by clockwork episodes of fever lasting 3-7 days, accompanied by aphthous stomatitis, pharyngitis, and/or cervical adenitis. Typically, patients with PFAPA are generally well between episodes and exhibit normal growth and development. Although PFAPA often resolves spontaneously, its recurrent nature can significantly impact quality of life, and symptoms may persist into adulthood. This narrative review aimed to consolidate current knowledge on PFAPA epidemiology, pathogenesis, clinical presentation, diagnostic considerations, and therapeutic options. A structured literature search was performed using PubMed, Cochrane Library, and Scopus, focusing on relevant articles specifically addressing PFAPA. Increasing evidence suggests multifactorial pathogenesis involving innate immune dysregulation, activation of the NLRP3 inflammasome, and Th1-driven inflammation. Genetic analysis studies suggest a polygenic inheritance of PFAPA, linking it to immune pathways shared with familial Mediterranean fever and Behçet's disease. Diagnosis remains clinical, though genetic testing may be warranted in specific cases. Management strategies vary owing to the absence of standardized guidelines. Oral corticosteroids are highly effective for acute episodes but may shorten the interval between flares. Among preventive therapies, colchicine appears to reduce attack frequency, although evidence of its efficacy is limited, while tonsillectomy is often considered curative but recommended for patients with refractory disease or when there is a concurrent otolaryngologic indication. Further research is needed to refine diagnostic criteria and optimize treatment strategies, ultimately improving patients' and caregivers' quality of life.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"575-592"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591959","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":"Long-Term Efficacy and Safety of Secukinumab in Children and Adolescents with Moderate-to-Severe Chronic Plaque Psoriasis: Four-Year Results of a Randomized, Phase III, Open-Label Trial.","authors":"Kulli Kingo, Philemon Papanastasiou, Stefan Beissert, Svetlana Lazareva, Asunción Vicente Villa, Jirina Bartonova, Rosalia Ballona, Amita Bansal, Ruvie Martin, Heng Fan, Charles O'Doherty, Shoba Ravichandran, Nina Magnolo","doi":"10.1007/s40272-025-00715-4","DOIUrl":"https://doi.org/10.1007/s40272-025-00715-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The efficacy and safety of secukinumab up to week 52 in children and adolescents with moderate-to-severe chronic plaque psoriasis have been demonstrated previously (NCT03668613). Herein, we report the long-term efficacy, safety, and tolerability of secukinumab over a period of up to 208 weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this randomized open-label trial, patients (6 to &lt; 18 years) were randomized 1:1 to receive low-dose (LD; N = 42) or high-dose (HD; N = 42) secukinumab stratified by weight (&lt; 25 kg, 25 to &lt; 50 kg, or ≥ 50 kg) and disease severity (moderate or severe). Patients weighing &lt; 25 kg received 75 mg secukinumab (both LD and HD); 25 to &lt; 50 kg received 75 mg (LD) or 150 mg (HD) secukinumab; and ≥ 50 kg received 150 mg (LD) or 300 mg (HD) secukinumab. The study assessed Psoriasis Area and Severity Index (PASI) 75/90/100 response, Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children's Dermatology Life Quality (CDLQI) 0/1 response, and safety. The impact of secukinumab treatment on physical development was also assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overall, 79.8% (67 of 84) enrolled patients completed 4 years of treatment (secukinumab LD [N = 31] and secukinumab HD [N = 36]). Both treatment groups showed sustained PASI and IGA mod 0/1 responses throughout the treatment period (at week 208, PASI 75/90/100 [secukinumab LD: 96.3%/88.9%/51.9%; secukinumab HD: 87.9%/81.8%/72.7%] and IGA mod 2011 0/1 [secukinumab LD: 85.2%; secukinumab HD: 84.8%]). Mean PASI score remained low in both treatment groups, from week 12 through week 208; at week 208, mean percentage change in PASI scores from baseline was - 95.7% (mean absolute score: 18.46 [baseline]; 0.76 [week 208]) with secukinumab LD and - 94.5% (mean absolute score: 19.25 [baseline]; 1.07 [week 208]) with secukinumab HD. CDLQI 0/1 response remained high in both treatment groups from week 12 through week 208 (secukinumab LD: 75.0%; secukinumab HD: 88.2%). Safety profile of secukinumab with long-term (~313.9 patient-years) treatment was favorable and in line with the known safety profile reported previously for 52-week treatment. No dose-dependent safety observations were noted. There were no deaths recorded throughout the entire duration of the treatment. Nonfatal serious adverse events (SAEs) were reported in four (9.5%) patients in the LD group (coronavirus disease 2019 [COVID-19], Crohn's disease, infectious mononucleosis, intentional self-injury, tibia fracture) and two (4.8%) patients in the HD group (appendicitis, tonsillitis). The incidence of treatment-emergent adverse events was similar in both secukinumab dose groups (LD [78.6%] and HD [83.3%]). No impact on the growth and development, or sexual maturation of pediatric patients, was noted with long-term treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Secukinumab demonstrated sustained long-term efficacy and improved quality of life through week 208 in pediatric pa","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964661","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":"https://doi.org/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":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}