29 research outputs found
Safety and Usage of C1-Inhibitor in Hereditary Angioedema: Berinert Registry Data
BackgroundThe plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; “pnfC1-INH”) is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis.ObjectiveThe objective of this study was to describe safety and usage patterns of pnfC1-INH.MethodsA multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety and usage data on subjects receiving pnfC1-INH for any reason.ResultsOf 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events/infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation.ConclusionsThe findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use
Bullous Eruption and Elevated Leukocyte Alkaline Phosphatase in the Course of Busulfan-Treated Chronic Granulocytic Leukemia
Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks
Background: Hereditary angioedema caused by C1 esterase
inhibitor deficiency is a rare disorder.
Objective: To compare the efficacy of pasteurized C1 esterase
inhibitor concentrate (Berinert, CSL Behring) at intravenous
doses of 10 or 20 U/kg body weight with placebo in the
treatment of single, acute abdominal or facial attacks in patients
with hereditary angioedema.
Methods: This was a randomized, double-blind, placebocontrolled study in 125 patients with type I or II hereditary
angioedema. The primary outcome was time from start of
treatment to onset of symptom relief. Secondary outcomes were
time to complete resolution, proportion of patients with
worsened intensity of angioedema symptoms between 2 and
4hours after treatment, and number of vomiting episodes within
4 hours.
Results: Median time to onset of relief was significantly shorter
with C1 esterase inhibitor concentrate at a dose of 20 U/kg than
with placebo (0.5 vs 1.5 hours; P 5.0025), whereas with 10 U/kg,
the time to onset of relief was only slightly shorter than with
placebo (1.2 vs 1.5 hours; P 5 .2731). Compared with placebo,
the reduction in time to onset of relief was greatest for severe
attacks (0.5 vs 13.5 hours). The secondary outcomes consistently
supported the efficacy of the 20 U/kg dose. C1 esterase inhibitor
concentrate was safe and well tolerated. No seroconversions
were observed for HIV, hepatitis virus, or human B19 virus.
Conclusion: C1 esterase inhibitor concentrate given
intravenously at a dose of 20 U/kg is an effective and safe
treatment for acute abdominal and facial attacks in patients
with hereditary angioedema, with a rapid onset of relief
Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks
The Historical Emergence of the Main Forms of Actors in the Middle East and North African Region
Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema
BACKGROUND: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.
METHODS: In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.
RESULTS: A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.
CONCLUSIONS: In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.