Second-line Therapy In Children Research Articles

Efficacy and safety of avatrombopag in Chinese children with persistent and chronic primary immune thrombocytopenia: A multicentre observational retrospective study in China.

Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO-RA) that has been recently approved as a second-line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second-line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty-four (18 males) patients with a mean age of 6.3 (range: 1.9-15.3) years were enrolled. The median number of previous treatment types was four (range: 1-6), and 41.2% patients switched from other TPO-RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1-27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1-3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second-line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs.

The Use of Ozenoxacin in Pediatric Patients: Clinical Evidence, Efficacy and Safety.

Impetigo is the most common childhood skin infection in the world. There are two patterns of impetigo: nonbullous (or impetigo contagiosa) and bullous. The nonbullous type is due to Staphylococcus aureus and group A beta-haemolytic Streptococcus and occurs in 70% of impetigo cases. Impetigo is often a self-limited disease, but complications can sometimes occur. Therapy depends on the extent and site of the lesions and on the presence of systemic symptoms. The increase in multidrug resistance pathogens, such as methicillin-resistant Staphylococcus aureus, mupirocin-resistant Staphylococcus aureus or quinolone-resistant Staphylococcus aureus, requires the development of new antibiotics against these agents. The aim of this review is to evaluate the efficacy and safety of ozenoxacin in children compared to those of other approved topical antimicrobial therapies. The bactericidal activity against both susceptible and resistant organisms is a relevant feature of ozenoxacin because the bacterial strain and potential for resistance are generally not known at the beginning of therapy. Additionally, its minimal dermal absorption and its capability to reach high concentrations in the upper layers of the epidermidis agrees with the recommended practice aimed at avoiding the emergence of bacterial resistance in presence of a good safety profile. Further studies with real-life analyses and pharmacoeconomic evaluation are needed to confirm its role as first-line and second-line therapy in children with impetigo.

Ketamine versus aminophylline for acute asthma in children: A randomized, controlled trial.

BACKGROUND:There is a lack of consensus regarding second-line therapy in children with acute asthma who fail to the standard therapy. Ketamine had bronchodilator property and may be useful in the treatment of acute asthma.OBJECTIVE:The objective of this study was to evaluate the efficacy and safety of ketamine as compared to aminophylline in children with acute asthma who respond poorly to the standard therapy.METHODS:This randomized controlled trial included patients with acute asthma having Pediatric Respiratory Assessment Measure (PRAM) score ≥5 at 2 h of standard therapy. The enrolled patients received either intravenous (IV) ketamine or IV aminophylline. Primary outcome measure was change in PRAM score at the end of intervention. Secondary outcome measures included adverse effects, change in PO2and PCO2, need for mechanical ventilation, and duration of hospital stay.RESULTS:The trial included 24 patients each in ketamine and aminophylline groups. The baseline parameters were similar between the groups. The primary outcome was similar in both the groups with a change in PRAM score of 4.00 ± 1.25 and 4.17 ± 1.68 (P = 0.699) in ketamine and aminophylline groups, respectively. The secondary outcomes were not different between the groups.CONCLUSION:Ketamine and aminophylline were equally effective for children with acute asthma who responded poorly to the standard therapy.

Switch to Subsequent Line of Treatment in Children and Adolescents with Chronic Myeloid Leukemia (CML) Treated with Imatinib: Experience of the International Registry for Chronic Myeloid Leukemia in Children and Adolescents (I-CML-Ped Study)

Aims: To determine in children and adolescents with chronic myeloid leukemia (CML) in chronic phase (CP) treated with imatinib front line, (i) the probability of switch to a second line therapy, (ii) to characterize the reasons and the type of switch and (iii) to determine the impact of the switch on outcome.Methods: Children and adolescents (<18 years) with CML diagnosed later than the year 2000 and enrolled in the international registry for childhood CML (I-CML-Ped Study) were the subjects of the study.Results: The I-CML-Ped study enrolled 301 children and adolescents with CML in CP treated with imatinib front line. Among them 112 patients subsequently switched to a second line therapy (median duration of imatinib treatment before the switch: 16 months [range: 1-111]).The probability of switch at 38 months was 50% (95% CI: 29-60). Primary resistance was the cause of switch in 47% of the patients: failure to achieve complete hematologic response (CHR, 1%), complete cytogenetic response (CCR, 20%) or major molecular response (MMR, 24%); not detailed (2%). A loss of response (CHR loss [2%] or CCR loss [4%] or MMR loss [13%]) or progression were the cause of switch in 19% and 4% of the patients, respectively. Occurrence of non hematologic toxicity (mainly muscle-skeleton pain) was the cause of switch in 10% of the patients. The reason of switch was the physician's choice in 20% of the patients (switch to hematopoietic stem cell transplantation [HSCT] while the patients were in MMR or deeper molecular response). The second line therapy consisted of second generation tyrosine kinase inhibitors (63%), chemotherapy (4%) or HSCT (33%). With a median follow up of 38 months (range: 2-150), overall, 8 deaths were recorded among switching patients: all were patients transplanted for acute phase (4 patients), hematologic resistance (1 patient), loss of hematologic response (1 patient) or physician's choice (2 patients). The causes of death were treatment related mortality (7 patients) and relapse (1 patient). One death only was recorded among the non switching patients. The probability of overall survival at 48 months was 90% (95% CI: 81% - 95%) for switching patients and 98% (95% CI: 89% - 100%) (p=0.005) for the non switching patients.Conclusion: Treatment failure is the main reason for a switch to a second line therapy in children and adolescents treated with imatinib front line. Efficacy of second line therapy still needs improvement. DisclosuresNo relevant conflicts of interest to declare.

1538 Use of Propranolol for Treating Epistaxis - First Experiences

Beta blockers are considered to be the most common prescribed class of drugs in treating cardiovascular diseases. However they are very useful in treating other conditions, such as migraine, glaucoma,...

Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis

Osteoprotegerin (OPG) is increased in inflamed colonic mucosa and has a role in immune regulation and apoptosis resistance. Fecal OPG may be useful in predicting corticosteroid resistance in hospitalized children with severe ulcerative colitis (UC). We aimed to determine whether fecal OPG predicts the need for second-line therapies in children hospitalized for UC. We included 83 children with UC admitted for intravenous corticosteroid treatment. Children were classified as responders/nonresponders based on the need for therapy escalation. Fecal OPG results were compared with those of four other fecal markers. Of the enrolled children, seven had day 1 samples only, 53 children had day 3 samples only, and 23 had both. Twenty-two children failed corticosteroid therapy and required infliximab (n = 20) or colectomy (n = 2). On the third treatment day the median fecal OPG levels were significantly higher in the nonresponders group compared with the responders: 77 pmol/L (interquartile range [IQR] 27-137) versus 13 pmol/L (3-109); P = 0.007. The best day 3 fecal OPG cutoff to predict second-line therapy was >50 pmol/L with a sensitivity of 71% and specificity of 69% (area under the receiver operator curve [ROC] of 0.70%-95% confidence interval [CI] 0.57-0.82). Fecal OPG was superior to day 3 fecal calprotectin, lactoferrin, and S100A12 as a predictor of corticosteroid nonresponse, but equivalent to the less commonly used M2-pyruvate kinase. Day 3 fecal OPG may guide the decision to institute second-line therapy in children with severe UC. The role of OPG in the inflammatory response in pediatric UC deserves further study.

Results of a phase II trial testing interferon‐alpha 2b and cytarabine in children and adolescents with chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a rare disease in children and only few data are available concerning the results of interferon based therapy in this age group. Before the imatinib mesylate era, a prospective phase II trial was conducted to assess the efficacy and tolerance of a combination of interferon-alpha 2b (IFN) and cytarabine in children with CML in first chronic phase without a suitable HLA-identical donor. Fourteen consecutive children were recruited from 12 pediatric centers. Children received daily IFN (5 million U/m2) and subcutaneous cytarabine (20 mg/m2) for 10 days every month. The median duration of follow-up is 13 months (range 2-32 months). Seven children achieved a complete hematologic response after a median time of treatment of 3 months (range 1 week-4 months). Three children were not evaluable for the cytogenetic response. A major cytogenetic response was achieved in seven patients (including complete cytogenetic response in two patient) within 12 months. The median time to major cytogenetic response was 7 months (range 3-12 months). Thirteen patients discontinued the treatment protocol after a median time of 11 months. Probability of progression free survival at 11 months was 83% (95% CI, 61%-100%). Grade 3 and 4 toxicity was observed in eight patients. The most frequently reported drug-related events were fever, mucositis, neutropenia, and thrombocytopenia. The combination of IFN and cytarabine provides hematologic and cytogenetic responses in children and adolescents with CML. In the imatinib mesylate era, the role of this combination as second line therapy in children with CML remains to be determined.