Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children.

BACKGROUND: Attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) usually begin during childhood or adolescence. However, limited data are available regarding indications and modalities of treatment of children. This study evaluated recombinant human C1-INH (rhC1-INH) for HAE attacks in children. METHODS: This open-label, phase 2 study included children aged 2-13 years with C1-INH-HAE. Eligible HAE attacks were treated intravenously with rhC1-INH 50 IU/kg body weight (maximum, 4200 IU). The primary end-point was time to beginning of symptom relief (TOSR; ≥20 mm decrease from baseline in visual analog scale [VAS] score, persisting for two consecutive assessments); secondary end-point was time to minimal symptoms (TTMS; <20 mm VAS score for all anatomic locations). RESULTS: Twenty children (aged 5-14 years; 73 HAE attacks) were treated with rhC1-INH. Seventy (95.9%) of the attacks were treated with a single dose of rhC1-INH. Seven (35.0%) children were treated for four or more attacks. Overall, median TOSR was 60.0 minutes (95% confidence interval [CI], 60.0-65.0); data were consistent across attacks. Median TTMS was 122.5 minutes (95% CI, 120.0-126.0); data were consistent across attacks. No children withdrew from the study due to adverse events. No treatment-related serious adverse events or hypersensitivity reactions were reported; no neutralizing antibodies were detected. CONCLUSIONS: Recombinant human C1-INH was efficacious, safe, and well tolerated in children. Data support use of the same dosing regimen for HAE attacks in children (50 IU/kg; up to 4200 IU, followed by an additional dose, if needed) as is currently recommended for adolescents and adults.

The Clinical Relevance of Various Hypersensitivity Tests in Patients with Atopic Dermatitis as Assessed by Their History, SCORAD Changes, and Number of Days with Need of Anti-Inflammatory Treatment.

Immediate and delayed hypersensitivity reactions can play a role in the pathogenesis of atopic dermatitis (AD). We tested 71 patients (median age 5 years) with AD for hypersensitivity to grass and birch pollen, Dermatophagoides pteronyssinus, and Dermatophagoides farinae using atopy patch test (APT), skin prick test (SPT), and specific IgE measurement. The sensitivity (SE) and specificity (SP) of the tests were calculated on the basis of personal history of AD exacerbation, clinical AD score (SCORAD) changes, and the number of days with need for topical anti-inflammatory treatment (AITD) in relation to exposure to the allergens being tested. APT was positive in 45 patients, mostly to D. farinae (n=37). SPT and/or specific IgE were positive in 42 subjects, in most cases to grass and birch pollen (n=29). SE of APT reached 33%-56% for history, 33% for SCORAD, and 0%-60% for AITD; SP of APT was comparable for all three assessment standards (history, SCORAD, and AITD) (48%-67%). SE of SPT/specific IgE was higher for history (26%-63%) than for the other two standards of assessment (0%-67%); SP of SPT/specific IgE was also highest for history (69%-91%), and lower for SCORAD (59%-87%) and AITD (65%-80%). AD is often associated with hypersensitivity; its influence on AD, however, is clinically significant only in a minor group of patients. While personal history and SCORAD changes present themselves as possible standards in the evaluation of clinically relevant hypersensitivity in AD patients, the anti-inflammatory treatment days (AITD) appears to be unsuitable for this purpose.