PMID- 30107868 OWN - NLM STAT- MEDLINE DCOM- 20190211 LR - 20190215 IS - 1539-6304 (Electronic) IS - 1088-5412 (Linking) VI - 39 IP - 5 DP - 2018 Sep 14 TI - Subcutaneous C1-esterase inhibitor to prevent hereditary angioedema attacks: Safety findings from the COMPACT trial. PG - 365-370 LID - 10.2500/aap.2018.39.4164 [doi] AB - BACKGROUND: The first subcutaneous (SC) C1-esterase inhibitor concentrate (C1-INH) was approved by the U.S. Food and Drug Administration in June 2017 as routine prophylaxis to prevent hereditary angioedema attacks in adolescents and adults at a dose of 60 IU/kg twice weekly based on the phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) trial. OBJECTIVE: This article aimed to evaluate the relationship of the C1-INH (SC) dose regimens tested in the COMPACT trial (40 IU/kg and 60 IU/kg twice weekly) and the occurrence of adverse events (AEs). METHODS: Patients were instructed to record any AEs in their e-diary daily. Safety and tolerability were assessed based on reported AEs, including injection-site reactions (ISRs); unsolicited AEs (AEs other than ISRs); serious AEs; thrombotic, thromboembolic, anaphylactic, hypersensitivity, sepsis, and bacteremia events; inhibitory antibodies to C1-INH; and clinically significant abnormalities in laboratory assessments. Information on ISRs was specifically solicited. RESULTS: No relationship between the dose of C1-INH (SC) and the incidence of ISRs or unsolicited AEs was observed. The proportion of injections followed by at least one ISR was 12% with C1-INH (SC) 40 IU/kg versus 5% with 60 IU/kg and 6% with placebo. No ISRs were serious or led to treatment discontinuation, and all resolved. There were no anaphylaxis, thromboembolic, sepsis, or bacteremia events reported during treatment with C1-INH (SC). All hypersensitivity AEs were nonserious, and the majority were assessed as being unrelated to treatment. No inhibitory antibodies to C1-INH were observed. CONCLUSION: C1-INH (SC) is safe and well tolerated with no dose-dependent safety concerns, as demonstrated in the COMPACT trial.Clinical trial NCT01912456, www.clinicaltrials.gov. FAU - Li, H Henry AU - Li HH AD - From the Institute for Asthma and Allergy, P.C., Chevy Chase, Maryl. FAU - Mycroft, Sarah AU - Mycroft S AD - CSL Behring, King of Prussia, Pennsylvania. FAU - Christiansen, Sandra AU - Christiansen S AD - Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California San Diego, La Jolla, California. FAU - Wood, Daniel N AU - Wood DN AD - CSL Behring, King of Prussia, Pennsylvania. FAU - Feuersenger, Henrike AU - Feuersenger H AD - CSL Behring, Marburg, Germany. FAU - Pawaskar, Dipti AU - Pawaskar D AD - CSL Behring, King of Prussia, Pennsylvania. FAU - Jacobs, Iris AU - Jacobs I AD - CSL Behring, King of Prussia, Pennsylvania. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20180814 PL - United States TA - Allergy Asthma Proc JT - Allergy and asthma proceedings JID - 9603640 RN - 0 (Complement C1 Inhibitor Protein) SB - IM MH - Angioedemas, Hereditary/complications/diagnosis/*drug therapy/prevention & control MH - Complement C1 Inhibitor Protein/administration & dosage/adverse effects/*therapeutic use MH - Disease Progression MH - Drug Hypersensitivity/etiology MH - Female MH - Humans MH - Male MH - Sepsis/etiology MH - Severity of Illness Index MH - Thromboembolism/etiology MH - Treatment Outcome EDAT- 2018/08/16 06:00 MHDA- 2019/02/12 06:00 CRDT- 2018/08/16 06:00 PHST- 2018/08/16 06:00 [pubmed] PHST- 2019/02/12 06:00 [medline] PHST- 2018/08/16 06:00 [entrez] AID - 10.2500/aap.2018.39.4164 [doi] PST - ppublish SO - Allergy Asthma Proc. 2018 Sep 14;39(5):365-370. doi: 10.2500/aap.2018.39.4164. Epub 2018 Aug 14.