Hereditary angioedema (HAE) is an autosomal dominant condition associated with episodic attacks of nonpitting edema. Patients with HAE have low levels of C1 inhibitor (a serine protease inhibitor). Edema is caused by unregulated generation of bradykinin.
C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia.
Classical and alternative complement pathways. Image source: Wikipedia.
Angioedema (AE) Classification (click to enlarge the image):
Angioedema (AE) can be allergic or non-allergic.
There are 5 types of non-allergic angioedema (AE):
- acquired AE
- hereditary AE (HAE)
- ACE-inhibitor induced AE
- idiopathic AE, can occur with chronic urticaria
- pseudoallergic AE, e.g. reaction to NSAIDs
There are 3 types of HAE that are differentiated by C4 and C1-INH levels
- type I HAE - low C4, low C1-INH function, low C1-INH antigen level
- type II HAE - low C4, low C1-INH function, normal C1-INH antigen level
- type III HAE - all normal
Effective chronic therapy for HAE has been available for decades -- androgens or plasmin inhibitors. Until recently, there was no therapy for acute attacks available in the U.S.
Treatment of acute HAE attacks
- C1-INH, 20 units/kg, IV infusion
- Icatibant, 30 mg SC, bradykinin B2 receptor antagonist
- Ecallantide, 30 mg SC, kallikrein receptor antagonist
Prophylaxis of HAE attacks
- C1-INH, 1,000 units, IV infusion every 3-4 days
- attenuated androgen, e.g. danocrine 200 mg PO TID
References
New Directions in the Treatment of Angioedema. Medscape, 2012.
http://www.medscape.org/viewarticle/759075
In recent years, 5 pharmaceutical companies have developed drugs which stop acute attacks of HAE or can be used for prophylaxis.
There are 2 preparations of C1 inhibitor purified from plasma which have been used in Europe for decades (Cinryze and Berinert P). There is also a recombinant C1 inhibitor (not obtained from plasma). A kallikrein inhibitor (Ecallantide) and a bradykinin type 2 receptor antagonist (Icatibant) are in testing phases. It is likely that HAE treatment will change dramatically in near future.
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New therapies for hereditary angioedema (HAE) (click to enlarge the image).
In summary, the new products for acute treatment and prophylaxis of hereditary angioedema (HAE) are:
- C1 inhibitor purified from plasma (Cinryze and Berinert P)
- recombinant C1 inhibitor. Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
- kallikrein inhibitor (Ecallantide)
- bradykinin type 2 receptor antagonist (Icatibant)
References:
New therapies for hereditary angioedema: Disease outlook changes dramatically. Frank et al. JACI, Volume 121, Issue 1, Pages 272-280 (January 2008).
New Directions in the Treatment of Angioedema. Medscape, 2012.
Hereditary angioedema, Supplement of Annals of Allergy, Asthma and Immunology, 01/2008.
Further reading:
Angioedema Due to Angiotensin Converting Enzyme Inhibitors. Allergy Cases, 01/2008.
Audio: New Therapies on Horizon for Angioedema Attacks. AAAAI, 03/2008.
HAE: annual drug cost alone for prophylactic C1 esterase inhibitor is $450k - nearly $5 mln for every decade of life http://goo.gl/BCVtu
Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
HAE patients can self-administer Berinert C1-INH by IV infusion - FDA, 2012.
C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia.
Classical and alternative complement pathways. Image source: Wikipedia.
Angioedema (AE) Classification (click to enlarge the image):
Angioedema (AE) can be allergic or non-allergic.
There are 5 types of non-allergic angioedema (AE):
- acquired AE
- hereditary AE (HAE)
- ACE-inhibitor induced AE
- idiopathic AE, can occur with chronic urticaria
- pseudoallergic AE, e.g. reaction to NSAIDs
There are 3 types of HAE that are differentiated by C4 and C1-INH levels
- type I HAE - low C4, low C1-INH function, low C1-INH antigen level
- type II HAE - low C4, low C1-INH function, normal C1-INH antigen level
- type III HAE - all normal
Effective chronic therapy for HAE has been available for decades -- androgens or plasmin inhibitors. Until recently, there was no therapy for acute attacks available in the U.S.
Treatment of acute HAE attacks
- C1-INH, 20 units/kg, IV infusion
- Icatibant, 30 mg SC, bradykinin B2 receptor antagonist
- Ecallantide, 30 mg SC, kallikrein receptor antagonist
Prophylaxis of HAE attacks
- C1-INH, 1,000 units, IV infusion every 3-4 days
- attenuated androgen, e.g. danocrine 200 mg PO TID
References
New Directions in the Treatment of Angioedema. Medscape, 2012.
http://www.medscape.org/viewarticle/759075
In recent years, 5 pharmaceutical companies have developed drugs which stop acute attacks of HAE or can be used for prophylaxis.
There are 2 preparations of C1 inhibitor purified from plasma which have been used in Europe for decades (Cinryze and Berinert P). There is also a recombinant C1 inhibitor (not obtained from plasma). A kallikrein inhibitor (Ecallantide) and a bradykinin type 2 receptor antagonist (Icatibant) are in testing phases. It is likely that HAE treatment will change dramatically in near future.
.jpg)
New therapies for hereditary angioedema (HAE) (click to enlarge the image).
In summary, the new products for acute treatment and prophylaxis of hereditary angioedema (HAE) are:
- C1 inhibitor purified from plasma (Cinryze and Berinert P)
- recombinant C1 inhibitor. Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
- kallikrein inhibitor (Ecallantide)
- bradykinin type 2 receptor antagonist (Icatibant)
References:
New therapies for hereditary angioedema: Disease outlook changes dramatically. Frank et al. JACI, Volume 121, Issue 1, Pages 272-280 (January 2008).
New Directions in the Treatment of Angioedema. Medscape, 2012.
Hereditary angioedema, Supplement of Annals of Allergy, Asthma and Immunology, 01/2008.
Further reading:
Angioedema Due to Angiotensin Converting Enzyme Inhibitors. Allergy Cases, 01/2008.
Audio: New Therapies on Horizon for Angioedema Attacks. AAAAI, 03/2008.
HAE: annual drug cost alone for prophylactic C1 esterase inhibitor is $450k - nearly $5 mln for every decade of life http://goo.gl/BCVtu
Recombinant C1 inhibitor is in phase III studies and should be available for HAE attacks in the near future http://goo.gl/Nxf8k
HAE patients can self-administer Berinert C1-INH by IV infusion - FDA, 2012.