Real-world Effectiveness of Lanadelumab in Hereditary Angioedema: Multi-country INTEGRATED Observational Study.

Background: Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent episodes of cutaneous or subcutaneous edema. There is clinical need for treatments that reduce the rate of HAE attacks in patients.

Objectives: Primary objectives were to evaluate the effectiveness of lanadelumab on attack free rate (AFR; proportion of patients who had zero HAE attacks), and on every two weeks (Q2W) and every four weeks (Q4W) adjustments on AFR.

The Icatibant Outcome Survey: 10 years of experience with icatibant for patients with hereditary angioedema.

In patients with hereditary angioedema (HAE), bradykinin causes swelling episodes by activating bradykinin B receptors. Icatibant, a selective bradykinin B receptor antagonist, is approved for on-demand treatment of HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing observational registry initiated in 2009 to monitor the effectiveness/safety of icatibant in routine clinical practice.

Hereditary angioedema due to C1 inhibitor deficiency: real-world experience from the Icatibant Outcome Survey in Spain.

Background: The Icatibant Outcome Survey (IOS) is an international registry monitoring the use of icatibant, a bradykinin B receptor antagonist indicated for the acute treatment of hereditary angioedema (HAE) attacks. Our goal was to assess disease characteristics and icatibant treatment outcomes in patients with HAE due to C1 inhibitor deficiency (HAE type 1 or 2 (HAE-1/2)) from Spain relative to other countries participating in IOS.

Methods: Descriptive retrospective analyses of data are reported from 10 centers in Spain vs 51 centers in 12 other participating countries (July 2009 to January 2019).

Management of hereditary angioedema in Japan: Focus on icatibant for the treatment of acute attacks.

Hereditary angioedema (HAE) is characterized by unpredictable, recurring and painful swelling episodes that can be disabling or even life-threatening. Awareness of HAE has progressively grown worldwide, and options for treatment of acute attacks and prevention of future attacks continue to expand; however, unmet needs in diagnosis and treatment remain. In Japan, recognition of HAE within the medical community remains low, and numerous obstacles complicate diagnosis and access to treatment.

Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey.

Background: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5-11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey.

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time.

Icatibant Outcome Survey in Patients with Hereditary Angioedema: Experience in Israel Compared with Other Countries.

Background: Management of patients with hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is evolving worldwide. Evaluating the Israeli experience may provide valuable insights.

Objectives: To compare demographics and icatibant treatment patterns and outcomes in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey (IOS) in Israel with those in other countries.

Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight: findings from the Icatibant Outcome Survey, a cohort observational study.

Background: Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. 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. 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.

Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the Icatibant Outcome Survey.

Background: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option.

Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting.

Background: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.

Objective: To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).

Subcutaneous immunoglobulin therapy for the treatment of multifocal motor neuropathy: a case report.

Multifocal motor neuropathy (MMN) is a rare immune-mediated disease characterized by slowly progressive, asymmetric, predominantly distal weakness of one or more limbs without sensory loss. The first line of treatment is high-dose intravenous immunoglobulins (IVIg). Subcutaneous immunoglobulins (SCIg)already approved for the treatment of primary immune deficiency have recently been proposed also for the treatment of disimmune peripheral neuropathies such as MMN, and a few trials were performed to see if patients receiving immunomodulatory doses of IVIg could be treated equally well with SCIg.

Anti-HLA antibody repertoire after IVIg infusion in highly sensitized patients waiting for kidney transplantation.

Polyclonal intravenous immunoglobulin (IVIg) treatment reduces crossmatch positivity and increases rates of transplantation in highly sensitised patients (HS). We quantified the panel reactive antibody (PRA) by microlymphocytotoxicity (MLCC), and we analysed anti-HLA class I and class II IgG specific antibody repertoire by Luminex before and after IVIg infusion alone in HS patients awaiting kidney transplantation. Five patients received three monthly infusions of 1 g/kg of IVIg.

Efficacy and safety of a new, chromatographically purified rhesus (D) immunoglobulin.

Objectives: To study the efficacy, safety, and tolerability of the 300 microg dose of a new chromatographically produced rhesus immunoglobulin (Rhophylac 300) for ante- and postnatal rhesus prophylaxis.

Design: In an open-label multi-centre study, rhesus D (RhD)-negative women were randomly allocated to receive Rhophylac 300 either intravenously or intramuscularly at the 28th week of gestation and within 72 h after delivery of an RhD-positive child. Serum samples were obtained prior to the antenatal dose and 6-11.

A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and FcgammaIIIA genes.

A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase 1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC) clearance, and prevention of RhD immunization in RhD-negative men challenged with 15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD effectively cleared RhD-positive RBCs after intravenous and intramuscular injection. The recombinant anti-RhD demonstrated a slower clearance rate compared with the polyclonal anti-RhD.

Reconstituted high-density lipoprotein exhibits neuroprotection in two rat models of stroke.

Background: Reconstituted high-density lipoprotein (rHDL) is prepared from apolipoprotein A-I, isolated from human plasma, and soybean-derived phosphatidylcholine and exhibits biochemical and functional characteristics similar to endogenous nascent high-density lipoprotein (HDL). This study tested the hypothesis that pretreatment with rHDL may reduce neuronal damage in 2 experimental rat models of stroke.

Methods: In the first model, an excitotoxic lesion was induced by unilateral injection of N-methyl-D-aspartate (NMDA) in the right striatum (excitotoxic lesion model).

Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein.

Background: Loss-of-function mutations in the ATP-binding cassette (ABCA)-1 gene locus are the underlying cause for familial hypoalphalipoproteinemia, providing a human isolated low-HDL model. In these familial hypoalphalipoproteinemia subjects, we evaluated the impact of isolated low HDL on endothelial function and the vascular effects of an acute increase in HDL.

Methods And Results: In 9 ABCA1 heterozygotes and 9 control subjects, vascular function was assessed by venous occlusion plethysmography.

Pharmacokinetics of anti-D IgG in pregnant RhD-negative women.

Objective: To assess the pharmacokinetics of anti-D IgG in pregnant Rhesus D-negative women after intramuscular and intravenous administration of 300 microg of Rhophylac.

Design: An open, randomised, multicentre study.

Setting: Seven gynaecological practices in Germany.