The use of tranexamic acid for on-demand and prophylactic treatment of hereditary angioedema-A systematic review

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and potentially life-threatening episodes of swelling in various parts of the body. These attacks can be painful and debilitating, and affect apatient’s quality of life. Every patient who experiences an attack should be treated with on-demand medication to mitigateattack severity and duration. Many patients with HAE also receive long-term prophylaxis to reduce the frequency and severity of edema episodes. Although long-term prophylaxis reduces the disease burden for patients with HAE, available intravenous and subcutaneous treatments are accompanied by a significant treatment burden because of the logistical, emotional, and physical challenges posed by their long-term parenteral nature. Androgens are an effective oral prophylactic treatment; however, they are associated with significant adverse events and are not suitable for all patients. Thus, the HAE community has expressed interest in the development of alternative oral prophylactic therapies for preventing HAE attacks.Objective: Here, we review the phase II and III clinical data of berotralstat (BCX7353), which was approved by the U.S. Food and Drug Administration in December 2020.Results: Berotralstat is an oral, second-generation, synthetic, small-molecule plasma kallikrein inhibitor taken once dailyfor the prevention of HAE attacks in patients ages greater than or equal to 12 years. Results from the APeX studies (APeX-1 NCT02870972, APeX-2 NCT03485911, APeX-S NCT03472040, APex-J NCT03873116) demonstrated the efficacy of berotralstat as longterm prophylaxis for patients with HAE, which showed a reduction in the attack rate and on-demand medication usage.Berotralstat was well tolerated, and gastrointestinal treatment-emergent adverse events were generally mild and selflimited.Conclusion: Oral berotralstat is an effective and safe long-term prophylactic treatment for patients with HAE that will provide patients unable to tolerate parenteral therapies with the option of disease control. Berotralstat may be associated with reduced treatment burden compared with injectable therapies, highlighting the importance of patient preference with regard tothe administration route of their HAE prophylactic treatment.

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Hereditary angioedema: On-demand treatment of angioedema attacks

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200066 ◽

2020 ◽

Vol 41 (6) ◽

pp. S26-S29

Author(s):

Sandra C. Christiansen ◽

Bruce L. Zuraw

Keyword(s):

Vascular Permeability ◽

Hereditary Angioedema ◽

Acute Treatment ◽

Prophylactic Treatment ◽

Unmet Needs ◽

Burden Of Illness ◽

Early Administration ◽

On Demand ◽

The Past ◽

Normal Life

The availability of effective acute treatment for angioedema has been fundamental in reducing the burden of illness for patients with hereditary angioedema (HAE). In building on the foundation of scientific advances that elucidate the pathomechanism(s) of attacks related to vascular permeability, novel targeted on-demand treatments have been developed and approved. These therapies have provided the means to arrest episodes of swelling, which, in the past, had the potential to inexorably lead to morbidity, and even mortality, for patients with HAE. Access to these medications, along with an emphasis on early administration and guidance that all attacks are candidates for treatment, has shifted the management paradigm for HAE. Although unmet needs remain, these acute therapies, coupled with advances in prophylactic treatment, have furthered the goal for all patients with HAE to live a normal life.

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Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01570-x ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Konrad Bork ◽

Thomas Machnig ◽

Karin Wulff ◽

Guenther Witzke ◽

Subhransu Prusty ◽

...

Keyword(s):

Genetic Testing ◽

Tranexamic Acid ◽

Hereditary Angioedema ◽

Factor Xii ◽

C1 Inhibitor ◽

Course Of Disease ◽

Specific Mutation ◽

Female Patients ◽

On Demand

Abstract Background Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type. Results A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family. Conclusions A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.

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Review of Type III Non-Hereditary Angioedema Patients in Manitoba.

10.21203/rs.3.rs-76142/v1 ◽

2020 ◽

Author(s):

Kelsey Hinther ◽

Chrystyna Kalicinsky

Keyword(s):

Hereditary Angioedema ◽

Prophylactic Treatment ◽

Retrospective Chart Review ◽

Inclusion Criteria ◽

Effective Response ◽

On Demand ◽

Efficacious Treatment ◽

Inhibitor Level ◽

High Index Of Suspicion ◽

And Function

Abstract Introduction: Non-hereditary angioedema with normal C1 esterase inhibitor level and function (NHAE-nC1INH) is a novel entity. The diagnosis of NHAE-nC1INH requires a high index of suspicion, given that there are no laboratory tests to confirm the diagnosis. There is limited evidence on the treatment efficacy for short- and long-term prophylaxis, and acute attacks. The aim of the study is to describe a cohort of NHAE-nC1INH in Manitoba, including an estimate of prevalence, as well as to analyze the response to plasma derived C1esterase inhibitor (pdC1INH), and a bradykinin-2 receptor antagonist (Icatibant).Methods: A retrospective chart review of patients diagnosed with normal C1 esterase level and function angioedema seen at the Clinical Immunology and Allergy Clinic at the Health Sciences Centre in Winnipeg, Manitoba, was done. Inclusion criteria included the following: (1) Reside within Manitoba (2) Aged 18 years and older (3) Angioedema without urticaria (4) Normal C1-INH antigenic level and function (5) No symptom resolution with antihistamines, epinephrine or corticosteroids. (6) No family history. Five patients were included in the study who met the above inclusion criteria. The five patients charts were reviewed. Response to pdC1INH and Icatibant were defined as time to improvement of angioedema symptoms.Results: Four out of five patients had an effective response to pdC1INH for prophylactic treatment and for on-demand treatment for angioedema episodes. pdC1INH was ineffective in 1 patient for prophylaxis and on-demand treatment; tranexamic acid was successful for prophylactic treatment in 1 patient who did not respond to pdC1INH for prophylaxis and for on-demand treatment. 3 of 5 patients have tried Icatibant. All three patients were not responsive to Icatibant.Conclusion: This study suggests that pdC1INH may be an efficacious treatment option for NHAE-nC1INH patients. Larger studies are required to better elucidate the effectiveness of on-demand and prophylactic treatment for NHAE-nC1INH.

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