Treatment Options

Unfortunately, in many countries there are currently no acute attack treatments available for HAE patients. In those countries physicians are therefore limited to providing patients with a short and long term prophylactic treatment with attenuated androgens (such as Danazol and Oxandrolone) and in some cases tranexamic acid (such as Cyklokapron). Although androgens are utilized in Canada, Health Canada has not approved them for the treatment of HAE.

An overview of treatment options

Until now, there is neither a cure for patients who suffer from HAE attacks nor a therapeutic concept to prevent these attacks completely.

Unlike allergic angioedema, HAE attacks do not respond to treatment with anti-histamines, corticosteroids or epinephrine.24 Current HAE treatment options focus on providing rapid relief during attacks or on the prevention of symptoms in patients who experience a high frequency of attacks or who undergo dental or surgical procedures which may trigger an attack.(8)

Acute treatment

The aim of acute treatment is to halt the progression of the edema and alleviate the symptoms. This applies particularly to episodes affecting the larynx, which can cause death by suffocation if left untreated.

The recommended options for acute treatment vary from country to country due to the fact that drugs for specific treatment are not licensed in all countries. In these cases acute treatment may be limited to more unspecific drugs such as tranexamic acid or even just pain killers.

In countries where it is available, C1-INH concentrate, Icatibant or Ecallantide can be used for the treatment of acute attacks. Icatibant can be administered by patients or caregivers after training by an health care provider. Ecallantide must be administered by subcutaneous injection by a healthcare professional, C1-INH concentrate must be administered intravenously.

Long-term prophylaxis

Long-term prophylaxis is given to patients whose quality of life is clearly reduced by the disease. These are usually patients who have either very frequent or very painful attacks or are at high risk of developing laryngeal edema.

Long-term prophylaxis consists mainly of attenuated androgens, synthetically produced derivatives of the male sex hormone testosterone. They can reduce the number of attacks. Because these medications are associated with a range of severe side-effects, attenuated androgens are generally reserved for patients suffering from frequent and/or severe symptoms. In the US, long-term prophylaxis with C1-INH concentrate has recently been approved. However in Canada, although utilized

In some countries, antifibrinolytic drugs such as tranexamic acid or aminocaproic acid are used as alternative to androgens.

Short-term prophylaxis

Short-term preventative therapy is recommended for patients undergoing dental procedures or surgery, which have been known to trigger an attack. One option for short-term prophylaxis consists of high dose androgen therapy for at least 5 days prior to surgery and 4 days afterwards. Where available, another option is to administer C1-INH concentrate approx. 1-2 hours prior to surgery.

Treatment of Acute Attacks

As might be expected from different pathogenesis, angioedema seen in HAE does not respond to the drugs employed in treating other forms of urticaria/angioedema such as antihistamines, epinephrine and corticosteroids. While epinephrine, in particular, may have a transient effect on swelling, it does not alter the course of an attack.

pdC1-INH is an effective therapy for the treatment of acute attacks.

The pdC1-INH is a human blood product. Treatment with pdC1-INH replaces the deficient protein in patients with HAE-1 and HAE-2……It has been licensed since 2010, and is available throughout Canada, through Canadian Blood Services or Hema-Quebec. It can be used to treat all attacks of HAE-1 and HAE-2 in adults and children. The recommended dosage is 20 U/kg administered intravenously either by healthcare professionals or by patients and their caregivers who have been trained in its administration. It has been shown to effectively treat acute attacks in pediatric and adult patients with HAE-1 and HAE-2 [22].

Icatibant is an effective therapy for the treatment of acute attacks.

Bradykinin is a key mediator in inducing angioedema through activation of the bradykinin B2 receptor [6]. Icatibant is a synthetic 10-amino acid peptide and acts as a selective bradykinin B2 receptor antagonist. It is administered as a single 30 mg subcutaneous injection. It has been shown to effectively treat acute attacks in adult patients with HAE-1 and HAE-2 [20, 25]. Icatibant is licensed in Europe and the USA for self-administration for the treatment of HAE attacks. (Addendum: Icatibant was licensed by Health Canada July 16, 2014). It is generally well-tolerated, although 90% of patients experience transient local pain, swelling, and erythema at the injection site.

Frozen plasma could be used for treatment of acute attacks if other recommended therapies are not available.

Early treatment likely leads to more rapid symptom resolution. Observational studies have suggested that early treatment can be efficacious in reducing the duration of an attacking some patients [38, 39, 40, 41, 42]. Therefore, despite the absence of a high level of evidence, expert opinion was strong endorsing early treatment in an attempt to reduce morbidity and likely mortality. Because of the potential barriers in accessing therapy in a timely manner, patients should be trained on how to self-administer therapies appropriate for the treatment of acute attacks of HAE. If patients are not able to self-administer their own therapy, efforts should be made to ensure that this therapy is made available to them without a significant delay (see Recommendation #21).

For more information on treatments for on-demand, home therapy, long-term prophylaxis and HAE with Normal C-1 visit:

HAE Clinical Trials Offer Hope for Better Therapeutic Alternatives

Six pharmaceutical companies are currently conducting or have recently concluded their HAE clinical trials. There will be continuously activities with each of the below mentioned pharmaceutical companies. Both with regards to clinical trials and to registration and licensing in new countries.

CSL Behring – C1-Inhibitor Concentrate (Trade name: Berinert)

Dyax Corp. – Kallikrein Inhibitor – Ecallantide (DX-88) (Trade name: Kalbitor)

Pharming NV – Recombinant C1-Inhibítor Concentrate (Trade name: Ruconest/Rhucin)

Sanquin – C1-Inhibitor Concentrate (Trade name: Cetor)

Shire Human Genetic Therapies (HGT) – B2 Bradykinin Receptor Antagonist – Icatibant (Trade name: Firazyr)

Viropharma – C1-Inhibitor Concentrate (Trade name: Cinryze)