The approved dose of icatibant in patients ≥ 18 years of age is 30 mg, and is based on clinical studies using a dose of 0.4 mg/kg body weight. Icatibant (Firazyr ® Shire, Zug, Switzerland) is a subcutaneously administered bradykinin B2 receptor antagonist that has demonstrated efficacy and safety for the treatment of acute attacks of C1-INH-HAE. C1-INH-HAE is caused by mutations in the SERPING1 gene, leading to C1-INH deficiency and subsequently elevated levels of bradykinin, the mediator of increased vascular permeability during attacks. Hereditary angioedema due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a genetic disease, affecting one in 50,000 people, with symptoms such as localized cutaneous swelling, abdominal pain, and laryngeal edema. Overall, icatibant was comparatively effective in treating attacks in patients across all BMI groups. Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal). Patients with obese BMI used pdC1-INH as rescue treatment more often (P < 0.0001 P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Most attacks (71.9–83.8%) were treated with a single icatibant injection without the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of BMI. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. Resultsĭata from 2697 icatibant-treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. MethodsĪttack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. Copyright © 2004 John Wiley & Sons, Ltd.Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. The standardized criteria defined in this paper, amino acid positions and property classes, will be useful to study the mutations and allele polymorphisms, to establish correlations between amino acids in the IG and TR protein three‐dimensional structures and to extract new knowledge from V‐like domains of chains, other than IG and TR, belonging to the immunoglobulin superfamily. They provide a characterization of the amino acid properties at each framework position of the expressed IG V‐REGIONs, and a visualization of the resemblances and differences between heavy and light, and between kappa and lambda sequences. Results of the analyses are shown as standardized two‐dimensional representations, designated as IMGT Colliers de Perles statistical profiles. Two statistical methods (correspondence analysis and hierarchic classification) were used to analyze the 237 framework positions (80 for IGHV, 79 for IGKV, 78 for IGLV), for three properties (hydropathy, volume and chemical characteristics) of the 20 common amino acids. The framework amino acid positions of 2474 V‐REGIONs (1360 IGHV, 585 IGKV, 529 IGLV) were numbered according to the IMGT unique numbering. In order to define the IMGT criteria necessary for standardized statistical analyses, the sequences of the IG variable regions (V‐REGIONs) from productively rearranged human IG heavy (IGH) and IG light kappa (IGK) and lambda (IGL) chains were extracted from IMGT/LIGM‐DB. IMGT comprises IMGT/LIGM‐DB, the comprehensive database of IG and TR sequences from human and other vertebrates (76 846 sequences in September 2003). IMGT, the international ImMunoGeneTics information system® () is a high‐quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates.
Pommié, Christelle Levadoux, Séverine Sabatier, Robert Lefranc, Gérard Lefranc, Marie‐Paule IMGT standardized criteria for statistical analysis of immunoglobulin V‐REGION amino acid properties IMGT standardized criteria for statistical analysis of immunoglobulin V‐REGION amino acid properties
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