Recombinant human C1 esterase inhibitor for hereditary angioedema attacks: A European registry.

Background: Hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling attacks. A European treatment registry was established to review the adverse event profile and efficacy of recombinant human C1 esterase inhibitor (rhC1-INH) for HAE attacks.

Methods: Individuals with C1-INH-HAE were enrolled following a decision to treat with rhC1-INH and provision of written informed consent.

Population pharmacokinetics of recombinant human C1 esterase inhibitor in children with hereditary angioedema.

Background: Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for the treatment of acute hereditary angioedema (HAE) attacks in adolescents and adults; it is also indicated in Europe for children aged 2 years and older. A need exists for further insight into potential pharmacokinetic (PK) differences in functional C1-INH levels by age (ie, children, adolescents, and adults).

Objective: To perform population PK modeling to predict C1-INH levels by age after by age rhC1-INH administration.

Modeling Cost-Effectiveness of On-Demand Treatment for Hereditary Angioedema Attacks.

Background: Hereditary angioedema (HAE) is a rare C1-inhibitor (C1-INH) deficiency disease. Low levels of functional C1-INH can lead to recurrent attacks of severe swelling occurring in areas such as the limbs, face, gastrointestinal tract, and throat. These attacks are both painful and disabling and, if not treated promptly and effectively, can result in hospitalization or death.

Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children.

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.

Efficacy of recombinant human C1 esterase inhibitor across anatomic locations in acute hereditary angioedema attacks.

Background: Hereditary angioedema (HAE) may occur at or spread to multiple anatomic locations during an acute attack. Recombinant human C1 esterase inhibitor (rhC1-INH) is approved for treating acute HAE attacks.

Objective: To examine the time to the beginning of symptom relief with rhC1-INH by attack location.

Recombinant human C1 esterase inhibitor for acute hereditary angioedema attacks with upper airway involvement.

Background: Recombinant human C1 esterase inhibitor (rhC1-INH) is approved for treatment of hereditary angioedema (HAE) in adolescents and adults. HAE attacks that involve the upper airway can be life threatening, and data on the administration of rhC1-INH for these types of attacks are currently limited.

Objective: To evaluate the efficacy and safety of rhC1-INH for treatment of acute HAE attacks with upper airway involvement.

Efficacy of recombinant human C1 esterase inhibitor for the treatment of severe hereditary angioedema attacks.

Background: Severe attacks of hereditary angioedema (HAE) are debilitating and potentially life threatening, and can increase anxiety and the use of medical resources.

Objective: This post hoc assessment evaluated recombinant human C1 esterase inhibitor (rhC1-INH) used to treat acute severe HAE attacks.

Methods: In a double-blind, randomized-controlled trial (RCT), patients with an HAE attack (baseline visual analog scale score of ≥50 mm, with severe attacks defined as ≥75 mm) were randomly assigned to receive rhC1-INH (50 IU/kg for patients who weighed <84 kg; 4200 IU for patients who weighed ≥84 kg) or placebo.

Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial.

Background: Hereditary angio-oedema is a recurrent, oedematous disorder caused by deficiency of functional C1 inhibitor. Infusions of plasma-derived C1 esterase inhibitor deter attacks of hereditary angio-oedema, but the prophylactic effect of recombinant human C1 esterase inhibitor has not been rigorously studied. We aimed to assess the efficacy of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema.

Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks.

Background: Symptoms of hereditary angioedema (HAE) attacks can recur soon after initial treatment; the durability of response for recombinant human C1 esterase inhibitor (rhC1INH) treatment is unknown.

Objective: To examine the efficacy and durability of rhC1INH for acute HAE attacks.

Methods: In this pooled post hoc analysis of 2 trials, patients with type I or II HAE (functional C1INH levels <50% of normal) and a baseline visual analog scale score of at least 50 mm were included if they had received at least 1 intravenous dose of 50 IU/kg of rhC1INH.

Recombinant Human C1-Esterase Inhibitor to Treat Acute Hereditary Angioedema Attacks in Adolescents.

Background: Recombinant human C1-esterase inhibitor (rhC1-INH) is efficacious and well tolerated for managing hereditary angioedema (HAE) attacks in adults. However, there are insufficient data on its efficacy and safety in adolescents.

Objective: To evaluate the efficacy and safety profiles of rhC1-INH for acute HAE attacks in adolescents.

C1 Inhibitor Limits Organ Injury and Prolongs Survival in Swine Subjected to Battlefield Simulated Injury.

Complement system activation is recognized as a deleterious component of the mammalian physiological response to traumatic injury with severe hemorrhage (TH). Female Yorkshire swine were subjected to a simulated austere prehospital battlefield scenario. Each animal underwent controlled hemorrhage of 22 mL/kg at 100 mL/min rate for approximately 10 min followed by soft tissue injury, femur fracture, and spleen injury.

Allergenicity and safety of recombinant human C1 esterase inhibitor in patients with allergy to rabbit or cow's milk.

Background: Recombinant human C1 inhibitor (rhC1INH) for on-demand treatment of hereditary angioedema is purified from milk of transgenic rabbits. It contains low amounts (<0.002%) of host-related impurities, which could trigger hypersensitivity reactions in patients with rabbit allergy (RA) and/or cow's milk allergy (CMA).

Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium.

Recombinant human-C1 inhibitor is effective and safe for repeat hereditary angioedema attacks.

Background: Hereditary angioedema (HAE) caused by a deficiency in functional C1 esterase inhibitor (C1INH) is characterized by recurrent episodes of cutaneous and/or mucosal/submucosal tissue swelling affecting multiple anatomic locations. Previous studies demonstrated efficacy of recombinant human C1INH (rhC1INH) for acute HAE attacks.

Objective: This study evaluated the efficacy and safety of rhC1INH (50 IU/kg) for the treatment of multiple HAE attacks in an open-label extension study.

Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking.

Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial.

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.

Population pharmacokinetics of recombinant human C1 inhibitor in patients with hereditary angioedema.

Aims: To characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients.

Methods: Plasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed-effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme.

Efficacy and safety of recombinant C1 inhibitor for the treatment of hereditary angioedema attacks: a North American open-label study.

Background: The efficacy of recombinant human C1 inhibitor (rhC1INH) for the treatment of patients with acute hereditary angioedema (HAE) attacks has been demonstrated in 2 randomized, double-blind, placebo-controlled studies.

Objective: To assess the safety and efficacy of rhC1INH for repeated treatment of acute attacks of HAE.

Methods: In this open-label extension study, patients with eligible HAE attacks were treated with an intravenous 50-U/kg dose of rhC1INH with an option for an additional dose of 50 U/kg based on clinical response.

Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.

Background: Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency.

Objective: The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions.

Methods: In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system.

Immunogenicity assessment of recombinant human c1-inhibitor: an integrated analysis of clinical studies.

Background And Objective: Recombinant human C1-inhibitor (rhC1INH) is used to treat acute angioedema attacks in hereditary angioedema (HAE) due to a genetic C1INH deficiency. Recombinant proteins in general may induce antibody responses and therefore evaluation of such responses in the target population is an essential step in the clinical development program of a recombinant protein. Here we report the assessment of the immunogenicity of rhC1INH in symptomatic HAE patients.