TY - JOUR
T1 - Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks
T2 - Phase 3, randomized, placebo-controlled trial
AU - Riedl, Marc A.
AU - Bernstein, Jonathan A.
AU - Li, Henry
AU - Reshef, Avner
AU - Lumry, William
AU - Moldovan, Dumitru
AU - Farkas, Henriette
AU - Levy, Robyn
AU - Baker, James
AU - Hardiman, Yun
AU - Totoritis, Mark C.
AU - Relan, Anurag
AU - Cicardi, Marco
N1 - Funding Information:
Disclosures: Dr Riedl has been a scientific consultant to Santarus Biocryst, CSL Behring, Dyax, Isis, Shire, and ViroPharma and received funding from Pharming CSL Behring, Dyax, Shire, and ViroPharma. Dr Baker has received funding from ViroPharma and Shire . Dr Rashef received grants from Shire HGT, Pharming BV, and Teva, Inc , research funding from Pharming BV and consulted for Shire HGT. Dr Moldovan received research fees from Pharming Technologies and CSL Behring. Dr Li received research fees from Pharming. Dr Farkas received consulting, speaking, and travel fees from CSL Behring, Shire, and SOBI. Dr Cicardi received research and educational grants from Shire and CSL Behring; served as speaker and on the advisory board of ViroPharma, SOBI, and Dyax and on the advisory board of BioCryst; and received a grant from Pharming. Dr Bernstein has served as speaker and consultant for Shire, Dyax, ViroPharma, and CSL Behring; received grants from Pharming, Dyax, Shire, ViroPharma, and CSL Behring; served on the board of directors for the American Academy of Allergy, Asthma, and Immunology, chair of Allergists for Israel, and editor in chief for the Journal of Asthma. Dr Lumry received consulting fees from BioCryst, CSL Behring, Shire HGT, and ViroPharma; served on the speaker's bureau of Shire HGT and ViroPharma; received grants from CSL Behring, Dyax, Shire HGT, and ViroPharma; and served on the medical advisory board of Hereditary Angioedema Association.
Funding Information:
Funding: This work was supported by Pharming Technologies BV (Leiden, the Netherlands) and Santarus, Inc (San Diego, California).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.
AB - Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.
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U2 - 10.1016/j.anai.2013.12.004
DO - 10.1016/j.anai.2013.12.004
M3 - Article
C2 - 24468257
AN - SCOPUS:84893684243
VL - 112
SP - 163-169.e1
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
SN - 1081-1206
IS - 2
ER -