![](https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhiwpYzdIzy39niVGgby951YzgBtPSBjnsRdUkA3fNWgfG4q8zLqfd4PwtYSmqYI9Xhc6KH0GO1dXMcT2c9EdwhhQEwXarde2FF1cNlUlfW73kHQOmgVKGsawqbhi3MHqgfuQiTRenOanM/s200/C1protein.png)
C1 protein, showing subunits C1r, C1s, and the C1q tails. Image source: Wikipedia.
![](https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPTA9acarw7mlDbcCIxT1TNU_VMlAEVwRdI7ShsIPvIoRT3tkcv5mTAS_iOeYRc9k2O3zuDyz1eO-zAjqrwc_rO_d49QCPvbHyr4uOdAw73SXzzbA-libBA-r47gtVrxzUXjPHxUlXwQk/s200/494px-Complement_pathway.png)
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.
![](https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi7fXGhHdxGlhBLJO4k5DiqBJWQw202bmgVzk2Z873V5T4nrXKc9WIZp2_Gf-VFZX6bbeYAEC3bIeVtglA-fMqReeMTUq4deJ0bvhSkURU_cxABQZX1bW_IUToqFmNj6oHFc8lklX6TKFE/s200/New_therapies_for_hereditary_angioedema_(HAE).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.
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