Monday 6th march 2017
Abstract AAAAI 2017
725 Recombinant Human C1 Inhibitor (rHC1INH) Is
Efficacious and Well Tolerated As Prophylaxis
for Prevention of Hereditary Angioedema (HAE)
Attacks: A Randomized, Phase 2 Trial
William H. Yang, MD, FAAAAI1
, H. H. Li2
, Chevy Chase, MD3
,
D. Moldovan3
, V. Grivcheva-Panovska4
, J. R. Harper5
, A. Relan6
, and
Marc A. Riedl, MD, MS7
; 1
Ottawa Allergy Research Corporation, Ottawa,
ON, Canada, 2
Institute for Allergy and Asthma, 3
University of Medicine
and Pharmacy, Mures County Hospital, Tirgu Mures, Romania, 4
PHU
Clinic of Dermatology, Medical University Skopje, Skopje, Macedonia,
The former Yugoslav Republic of, 5
Salix Pharmaceuticals, Raleigh, NC, 6
Pharming Technologies BV, Leiden, Netherlands, 7
University of California,
San Diego, La Jolla, CA.
RATIONALE: rhC1INH is currently administered for the treatment of
acute HAE attacks. Repeat rhC1INH treatment for recurrent attacks during
open-label extension studies have maintained efficacy while being well
tolerated, supporting a potential role for rhC1INH in prophylaxis.
METHODS: A randomized, double-blind, 3-period, crossover study was
conducted in patients >_13 years of age with functional C1INH levels <50%
of normal and >_4 HAE attacks during the previous 3 months. Patients
received rhC1INH 50 IU/kg (max, 4200 IU) once or twice weekly or
placebo in three, 4-week periods; each treatment was separated by 1 week
and symptoms monitored by a daily diary. Primary endpoint was number of
HAE attacks per 4-week period. Additional endpoints included percentage
of patients with >_25%, >_50% (clinical response), or >_75% reduction in
number of HAE attacks versus placebo and number of days with HAE
symptoms.
RESULTS: Thirty-two patients were randomized (mean age, 45.9 years
[range, 16.9–73.5 years]). Mean number of HAE attacks was reduced from
7.2 (placebo) to 4.4 (rhC1INH once weekly; P50.0004) and 2.7 (rhC1INH
twice weekly; P<0.0001). Percentage of patients with >_25%, >_50%, and
>_75% reduction in HAE attacks versus placebo was 64.5%, 41.9%, and
19.4% for rhC1INH once weekly and 80.6%, 74.2%, and 41.9%
rhC1INH twice weekly, respectively. Number of days with HAE symptoms
was lower with rhC1INH twice weekly (5.1 days) and once weekly (8.0
days) versus placebo (10.2 days).
CONCLUSIONS: rhC1INH was efficacious for the prevention of HAE
attacks and data support continued investigation of rhC1INH as
prophylaxis.
736 Efficacy of Recombinant Human C1 Esterase
Inhibitor (rhC1INH) Across Anatomical Locations
in Acute Hereditary Angioedema (HAE) Attacks
James W. Baker, MD, FAAAAI1
, Jonathan A. Bernstein, MD,
FAAAAI2
, J. R. Harper3
, A. Relan4
, and Marc A. Riedl, MD, MS5
; 1
Baker
Allergy Asthma and Dermatology, Lake Oswego, OR, 2
University of Cincinnati
College of Medicine, Cincinnati, OH, 3
Salix Pharmaceuticals, Raleigh,
NC, 4
Pharming Technologies BV, Leiden, Netherlands, 5
University
of California, San Diego, La Jolla, CA.
RATIONALE: rhC1INH is efficacious for acute HAE attacks. It is
important to understand if differences in time to symptom relief may vary
by anatomical attack location.
METHODS: Data were pooled from 2 randomized, double-blind,
placebo-controlled studies with open-label extensions. Patients >_12 years
of age with an acute HAE attack received rhC1INH 50 U/kg or placebo.
Time to beginning of symptom relief was defined as first timepoint that
severity visual analog scale (VAS) score at an attack location decreased by
>_20 mm versus baseline, with persistence to next timepoint. Data reported
as mean (95% confidence interval).
RESULTS: For all attack locations assessed, rhC1INH treatment shortened
time to beginning of symptom relief. Time to beginning of symptom
relief for an abdominal attack for rhC1INH (n5194) was 60.0 minutes
(47.0, 62.0) and for placebo (n515) was 240.0 minutes (45.0, 720.0). For a
peripheral attack, the time to for rhC1INH (n5169) was 105.0 minutes
(90.0, 120.0) and the time to for placebo (n517) was 303.0 minutes (180.0,
720.0). Time to beginning of symptom relief for an oro-facial-pharyngeallaryngeal
attack for rhC1INH (n536) was 64.5 minutes (60.0, 120.0) and
for placebo (n56) time to was 306.0 minutes (30.0, 495.0). For a facial
attack, the time to for rhC1INH (n524) was 158.0 minutes (90.0, 330.0);
placebo (n52) could not be determined. For a urogenital attack, rhC1INH
(n513) was 119.0 minutes (40.0, 270.0), and for placebo (n51) was 320.0
minutes.
CONCLUSIONS: Treatment with rhC1INH 50 U/kg was efficacious in
shortening time to symptom relief of acute HAE attacks, regardless of
attack location.