PMID- 30993784 OWN - NLM STAT- MEDLINE DCOM- 20200331 LR - 20210109 IS - 1399-3038 (Electronic) IS - 0905-6157 (Print) IS - 0905-6157 (Linking) VI - 30 IP - 5 DP - 2019 Aug TI - Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children. PG - 562-568 LID - 10.1111/pai.13065 [doi] AB - 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. CI - (c) 2019 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd. FAU - Reshef, Avner AU - Reshef A AUID- ORCID: 0000-0002-3324-7072 AD - Barzilai University Hospital, Ashkelon, Israel. FAU - Grivcheva-Panovska, Vesna AU - Grivcheva-Panovska V AD - Medical University Skopje, Skopje, North Macedonia. FAU - Kessel, Aharon AU - Kessel A AUID- ORCID: 0000-0003-4141-2100 AD - Technion Faculty of Medicine, Bnai Zion Medical Center, Haifa, Israel. FAU - Kivity, Shmuel AU - Kivity S AD - The Tel Aviv Medical Center, Tel Aviv, Israel. FAU - Klimaszewska-Rembiasz, Maria AU - Klimaszewska-Rembiasz M AD - Pediatric Hospital, Krakow, Poland. FAU - Moldovan, Dumitru AU - Moldovan D AD - MediQuest Clinical Research, Sangeorgiu de Mures, Romania. FAU - Farkas, Henriette AU - Farkas H AD - Semmelweis University, Budapest, Hungary. FAU - Gutova, Vaclava AU - Gutova V AD - Institute of Immunology and Allergology, Pilsen, Czech Republic. FAU - Fritz, Stephen AU - Fritz S AD - Portland Clinical Research, Portland, Oregon, USA. FAU - Relan, Anurag AU - Relan A AD - Pharming Healthcare Inc., Bridgewater, New Jersey, USA. FAU - Giannetti, Bruno AU - Giannetti B AD - Pharming Group NV, Leiden, The Netherlands. FAU - Magerl, Markus AU - Magerl M AD - Charite Universitatsmedizin Berlin, Berlin, Germany. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190529 PL - England TA - Pediatr Allergy Immunol JT - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology JID - 9106718 RN - 0 (Complement C1 Inhibitor Protein) RN - 0 (Recombinant Proteins) SB - IM MH - Administration, Intravenous MH - Adolescent MH - Angioedemas, Hereditary/*drug therapy MH - Body Weight MH - Child MH - Child, Preschool MH - Clinical Protocols MH - Complement C1 Inhibitor Protein/*therapeutic use MH - Drug Dosage Calculations MH - Female MH - Humans MH - Male MH - Recombinant Proteins/*therapeutic use MH - Treatment Outcome PMC - PMC6851822 OTO - NOTNLM OT - angioedema OT - child OT - complement C1 inactivator proteins OT - complement C1s OT - hereditary OT - hereditary angioedema type I and type II OT - recombinant proteins COIS- Avner Reshef reports receiving honoraria from CSL Behring and receiving research grants to institution funding from BioCryst Pharmaceuticals, Inc., CSL Behring, Pharming Group NV, Shire HGT, Stallergenes Greer, and Teva. Vesna Grivcheva-Panovska reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Aharon Kessel reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Shmuel Kivity reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Maria Klimaszewska-Rembiasz reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Dumitru Moldovan reported having ties to BioCryst Pharmaceuticals, Inc., CSL Behring, Pharming Technologies BV, Shire HGT, and Swedish Orphan Biovitrum AB. Henriette Farkas reports serving as principal investigator for clinical trials sponsored by Pharming Group NV, and receiving consultancy/speaker fees and honoraria from BioCryst Pharmaceuticals, Inc., CSL Behring, Pharming Group NV, and Shire HGT. Vaclava Gutova reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Stephen Fritz reports serving as principal investigator for clinical trials sponsored by Pharming Group NV. Anurag Relan reports being an employee of Pharming Healthcare, Inc. Bruno Giannetti reports being an employee of Pharming Group NV. Markus Magerl reports receiving honoraria from BioCryst Pharmaceuticals, Inc., CSL Behring, Pharming Group NV, and Shire HGT, and serving as principal investigator for clinical trials sponsored by BioCryst Pharmaceuticals, Inc., CSL Behring, Pharming Group NV, and Shire HGT. EDAT- 2019/04/18 06:00 MHDA- 2020/04/01 06:00 PMCR- 2019/11/13 CRDT- 2019/04/18 06:00 PHST- 2018/12/04 00:00 [received] PHST- 2019/04/02 00:00 [revised] PHST- 2019/04/04 00:00 [accepted] PHST- 2019/04/18 06:00 [pubmed] PHST- 2020/04/01 06:00 [medline] PHST- 2019/04/18 06:00 [entrez] PHST- 2019/11/13 00:00 [pmc-release] AID - PAI13065 [pii] AID - 10.1111/pai.13065 [doi] PST - ppublish SO - Pediatr Allergy Immunol. 2019 Aug;30(5):562-568. doi: 10.1111/pai.13065. Epub 2019 May 29.