Marco Cicardi

• MD
• Manager at Ospedale Luigi Sacco - University of Milan

Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potential...

Following the publication of the original article [1] the authors informed us of an error in the second paragraph under ‘Study population’ of the ‘Results’ section.

Enzyme-linked immunosorbent assay (ELISA) is a quantitative analytical method used to measure the concentration of molecules in biological fluids through antigen-antibody reactions. Here we describe the measurement of anti-C1-inhibitor autoantibodies by an indirect ELISA. In this method patients’ sera are incubated in a microplate coated with plasm...

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to dia...

Background: Long-term prophylaxis with subcutaneous C1-inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) in patients with hereditary angioedema (HAE) due to C1-INH deficiency (C1-INH-HAE) was evaluated in an open-label extension follow-up study to the international, double-blind, placebo-controlled COMPACT study. The current analysis evaluated patient...

Background: Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this...

An amendment to this paper has been published and can be accessed via the original article.

Background: Hereditary angioedema (HAE) due to C1 inhibitor (C1INH) deficiency is characterized by recurrent attacks of edema of the skin and mucosal tissues. Symptoms usually present during childhood (mean age at first attack, 10 years). Earlier symptom onset may predict a more severe disease course. Subcutaneous (SC) C1INH is indicated for routin...

Immune Thrombocytopenic Purpura (ITP) is an autoimmune thrombocytopenia with a shortened platelet survival and relative bone marrow failure. The pathogenesis involves antibody production, cytokine release, T‐cell impairment, complement activation, and clearance of platelets. We measured plasma levels of C3, C4, C1q, and sC5b‐9 in 80 ITP patients in...

An impairment of the endothelial barrier function underlies a wide spectrum of pathological conditions. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) can be considered the “pathophysiological and clinical paradigm” of Paroxysmal Permeability Diseases (PPDs), conditions characterized by recurrent transient primitively functional...

Background Patients affected by angioedema due to hereditary and acquired C1-inhibitor (C1-INH) deficiency (HAE and AAE, respectively) report trouble accessing dental care, due to the risk of a life-threatening oropharyngeal and laryngeal attack triggered by dental procedures. The aim of this study was to assess the identification of hurdles in rec...

Background Hereditary angioedema (HAE) comprises HAE with C1‐inhibitor deficiency (C1‐INH‐HAE) and HAE with normal C1‐INH activity (nl‐C1‐INH‐HAE), due to mutations in factor XII (FXII‐HAE), plasminogen (PLG‐HAE), angiopoietin 1 (ANGPT1‐HAE), kininogen 1 genes (KNG1‐HAE), or angioedema of unknown origin (U‐HAE). The Italian network for C1‐INH‐HAE (...

Isolated angioedema, which is a localized, non‐pitting, and transient swelling of the subcutaneous or submucosal tissue not associated with pruritus, urticaria, or anaphylaxis, may be classified, based on genetic pattern and mediators, respectively, as acquired or hereditary and histamine‐ or non‐histamine‐induced. The pediatric population with C1‐...

Hereditary angioedema (HAE) is a rare autosomal dominant disorder mostly due to the deficiency of C1-esterase inhibitor (C1-INH). Reduced C1-INH activity below ~38% disrupts homeostasis of bradykinin (BK) formation by increasing kallikrein activation and causes recurrent angioedema attacks affecting the face, extremities, genitals, bowels, orophary...

Abstract Background Hereditary angioedema (HAE) is a debilitating disorder resulting from C1-esterase inhibitor (C1-INH) deficiency. In the COMPACT phase 3 study the prophylactic use of a subcutaneous C1 inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) twice weekly significantly reduced the frequency of acute edema attacks. Analysis of treatment eff...

Abstract This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is t...

Introduction: Hereditary angioedema (HAE) with C1 esterase inhibitor deficiency (C1-INH-HAE) is a rare disease that manifests with cutaneous and/or submucosal swellings due to uncontrolled activation of the contact/kinin system. Attacks recur with unpredictable frequency and severity, laryngeal edema is potentially lethal, and the disease burden ma...

Evidence accumulated over the last two decades indicates that recurrent angioedema without wheals constitutes a diverse family of disorders with a much higher complexity than was previously regarded. Indicatively, during the last two years, novel variants of three genes other than SERPING1 and F12 have been identified in association with hereditary...

Background: Hospitalized patients are frequently treated with opioids for pain control, and receipt of opioids at hospital discharge may increase the risk of future chronic opioid use. Objective: To compare inpatient analgesic prescribing patterns and patients' perception of pain control in the United States and non-US hospitals. Design: Cross...

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. Methods The Ica...

Idiopathic systemic capillary leak syndrome (ISCLS) presents with recurrent potentially life-threatening episodes of hypovolemic shock associated with severe hemoconcentration and hypoproteinemia. Timely recognition is of paramount importance because ISCLS, despite resembling other kinds of hypovolemic shock, requires a peculiar approach, to preven...

Background: Paroxysmal Permeability Disorders (PPDs) are pathological conditions caused by periodic short lasting increase of endothelial permeability, in the absence of inflammatory, degenerative, ischemic vascular injury. PPDs include primary angioedema, idiopathic systemic capillary leak syndrome and some rare forms of localized retroperitoneal-...

Introduction: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is a rare disease with unpredictable, self-limiting and localized swelling episodes involving the cutaneous and subcutaneous tissues. In the last decade, the spectrum of the possibilities to control the disease has considerably changed with the development of biologic therapi...

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objec...

Background Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent edema of unpredictable frequency and severity. Stress, anxiety, and low mood are among the triggering factors most frequently reported. Impaired regulation and processing of emotions, also known as alexithymia, may influence outcomes. The aim of...

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by episodes of acute subcutaneous swelling, and/or recurrent severe abdominal pain. The disease is potentially fatal if the upper-airway is involved. Iatrogenic harm can occur if HAE is not considered in the differential d...

Introduction Lanadelumab est un anticorps monoclonal qui inhibe la kallikréine plasmatique et possède une demi-vie d’environ 14 jours. Il s’est avéré efficace pour la prévention des crises d’angio-œdème héréditaire (AOH) dans l’étude de phase 3 HELP (NCT02586805). Dans l’étude HELP, la pharmacocinétique et la pharmacodynamique du lanadelumab ont ét...

Hereditary angioedema is a rare and disabling disease characterized by severe, acute, self-limiting edema of the subcutaneous and mucosal tissue. The disease carries significant mortality when the upper airways are involved. It is determined by a transient dysregulation in vascular permeability with a sudden increase in fluid extravasation. The mos...

Importance Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants Phase 3, randomized, double-blind,...

Introduction Replacement therapy with subcutaneous C1-esterase inhibitor (C1-INH[SC]) 60 IU/kg twice weekly is approved for routine prophylaxis to prevent hereditary angioedema (HAE) attacks. Coagulation and fibrinolytic parameters levels tend to be elevated in HAE patients. We evaluated the effects of C1-INH(SC) on these parameters. Methods In th...

Introduction In the HELP Study (NCT02586805), treatment with lanadelumab (a monoclonal antibody inhibitor of plasma kallirein) 150 mg q4wks, 300 mg q4wks, or 300 mg q2wks significantly decreased attack rates over 26 weeks. We evaluated the relationship between lanadelumab exposure and efficacy during steady state (days 70-182) among the 3 dose grou...

Introduction In women with hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency, pregnancy can have a variable effect on disease activity. C1-INH concentrate is recommended as first-line therapy for pregnant patients with HAE. Subcutaneous C1-INH (HAEGARDA®, CSL Behring) is indicated for routine prophylaxis to prevent HAE attacks in...

Introduction Hereditary angioedema (HAE) is characterized by unpredictable attacks of debilitating swelling. APeX-1 was a Phase 2, double-blind, placebo-controlled study to evaluate the prevention of attacks with BCX7353, a once daily oral kallikrein inhibitor, in patients with HAE. Methods Patients with Type I or II HAE with a history of at least...

Introduction Subcutaneous human C1-inhibitor [C1-INH(SC)] is approved for prevention of angioedema attacks based on the Phase 3 COMPACT trial results. This extension study provides long-term data on efficacy and safety of C1-INH(SC). Methods This open-label, multicenter, randomized, parallel-arm study enrolled patients diagnosed with hereditary an...

Angioedema due to acquired deficiency of the inhibitor of the first component of complement (C1-INH) is a rare disease known as acquired angioedema (AAE). About 70% of patients with AEE display autoantibodies to C1-INH, the remaining patients have no antibodies to C1-INH. The clinical features of C1-INH deficiency include recurrent, self-limiting l...

Background Hereditary angioedema is a life-threatening illness caused by mutations in the gene encoding C1 inhibitor (also called C1 esterase inhibitor) that lead to overactivation of the kallikrein–bradykinin cascade. BCX7353 is a potent oral small-molecule inhibitor of plasma kallikrein with a pharmacokinetic and pharmacodynamic profile that may...

Introduction: Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is a debilitating and potentially lethal disease. Management includes on-demand treatment of angioedema and their prophylaxis. Plasma derived C1-INH is an established treatment for both on demand and prophylaxis of HAE. Conestat alfa is a recombinant form of human C1-...

Background Long‐term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma‐derived C1 esterase inhibitor (C1‐INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention. Objective To characterize the population pharmacokinetics of C1‐INH (SC) (HAEGARDA®; C...

Background Hereditary angioedema (HAE) caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) is a disabling, potentially fatal condition characterized by recurrent episodes of swelling. We have recently found that patients with C1-INH-HAE have increased plasma levels of vascular endothelial growth factors a...

Objectives To explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments. Design Cost analyses and survival analyses using attack-level dat...

Background: Hereditary Angioedema (HAE) due to C1-inhibitor deficiency is a lifelong illness characterized by recurrent acute attacks of localized skin or mucosal edema. An activation of the kallikrein/bradykinin pathway at endothelial cell level has a relevant pathogenetic role in acute HAE attacks. Moreover, other pathways are involved, given th...

Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease that involves the endothelium and microcirculation, leading to an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. The consequence of the capillary leakage is a life-threatening hypovolemic shock that can lead to lethal multiple organ dy...

Supplementary Text and Table: 2017.10.11 Exposure‐response analysis publication supplementary RESUBMISSION FINAL.docx Table S1. Summary of covariate testing using WAM and NONMEM.

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mec...

C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mec...

Subcutaneous C1-inhibitor (HAEGARDA, CSL Behring), is a US Food and Drug Administration (FDA)-approved, highly concentrated formulation of a plasma-derived C1-esterase inhibitor (C1-INH), which, in the phase III Clinical Studies for Optimal Management in Preventing Angioedema with Low-Volume Subcutaneous C1-inhibitor Replacement Therapy (COMPACT) t...

Background Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i....

This symposium provided an overview of past, current, and future therapies and routes of administration for patients with hereditary angioedema (HAE). Prof Cicardi opened the symposium by welcoming attendees and introducing the main topics of the session. Prof Magerl then focussed on treatments that are currently used for acute and prophylactic man...

Background Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes. Objective Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation. Methods Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) durin...

Angioedema—De-identified data set. The raw data set from which results have been derived is available as de-identified data set included as a Supporting Information File. (XLSX)