angioedema is a rare genetic disorder in which the patient suffers
from attacks of swelling of the tissues just below the skin and mucous
membranes in several parts of the body including the face, abdomen and limbs
. The number
of attacks, the severity of the attacks and the sites affected vary from person
to person. The attacks can occur spontaneously, or can be triggered by
conditions like stress, surgery or infection.
‘The FDA approval of a C1-esterase inhibitor (human) to prevent attacks of hereditary angioedema can prevent the appearance of life-threatening swellings in patients with the genetic disorder.’
abdominal organs can result in pain, vomiting and diarrhea. Swelling of the
face causes temporary disfigurement. If the tissues of the throat (larynx) are
involved, breathing can get affected. The condition can therefore be
affected individuals lack the functional form of a protein called C1-esterase
inhibitor (C1-INH). C1-INH controls inflammation mediated by chemicals which
constitute the 'complement system'
. In the absence of the protein, the
inflammatory process goes unchecked, resulting in seepage of fluid from the
blood vessels into the surrounding tissues and swelling of various tissues. The
disease may be inherited from parents or may occur due to a new genetic
mutation in the baby.
are three types of hereditary angioedema, types 1, 2 and 3
. Type 1
occurs due to deficient C1-INH. In type 2 hereditary angioedema, the C1-INH is
present but dysfunctional C1-INH. The C1-INH in type 3 disease is normal, and
the exact cause of the condition is not known.
Attacks of hereditary
angioedema are treated with special drugs like recombinant human C1-INH,
ecallantide and icatibant
which arrest the inflammatory process.
Drugs like danazole
have been used for the prevention of
hereditary angioedema. An intravenous C1-esterase inhibitor is also available
but may be more inconvenient to use as compared to a subcutaneous preparation.
recent approval of the subcutaneous C1 Esterase Inhibitor (Human) for the
prevention of hereditary angioedema attacks comes following its successful use
in the Phase III COMPACT trial
. In this trial, the treatment was tested
in patients with type 1 or type 2 hereditary angioedema between the ages of 12
and 72 years. Out of the 90 patients included in the study, some received the
injection twice a week in doses of 40 IU/kg or 60 IU/kg for 16 weeks, while
others received a placebo. The study concluded that:
- Patients in the
group that received the medication experienced a considerable reduction in
the number of attacks of hereditary angioedema as compared to those who
received only placebo.
- The subcutaneous
injections restored the level of C1-INH to more than 40%
- Adverse effects
included allergic reactions, nasal and throat swelling and dizziness
The medication should
not be used in patients who had previously suffered from serious allergic
reactions with a C1-INH preparation or its inactive ingredients. In addition,
it cannot be used to treat the attacks.
- FDA approves first subcutaneous C1 Esterase Inhibitor to treat rare genetic disease - (https:www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm564332.htm)
- Longhurst H et al. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med 2017; 376:1131-1140 DOI: 10.1056/NEJMoa1613627