Prematta et al potential to be quite beneﬁcial. Patients receive treatment much earlier than they otherwise might, which reduces the duration of symptoms. In addition, the prophylactic portion demonstrated that weekly to biweekly injections could reduce and at times eliminate attacks. Discussion C1-INH concentrate has been available in parts of Europe for over 20 years with many studies showing strong evidence that it signiﬁcantly shortens an acute HAE attack. However, many of the studies are based on retrospective data because until recently, only a limited number of randomized, placebo- controlled, double-blind clinical trials to establish its efﬁcacy were available. Ethically, it is difﬁcult to withhold C1-INH concentrate to a patient with an acute attack because some attacks can be very serious or fatal; therefore, most studies have used open-label C1-INH concentrate for urgent condi- tions in patients receiving the placebo. Multiple groups have presented their data for C1-INH concentrate with apparent success, but given the fact that an acute attack can have an unpredictable course with sudden worsening or improvement, it is difﬁcult to prove efﬁcacy without assessing varied doses in a placebo-controlled and double-blinded clinical trial. Several recent articles have demonstrated the efﬁcacy of C1-INH concentrate for the treatment of acute HAE attacks. The doses given in these studies have ranged from 400 to 1000 U and in other studies have ranged from 10 to 25 U/kg body weight. The most recent studies used 20 U/kg body weight as the dose for treatment. Several groups have demonstrated that the time from infusion to the beginning of relief of symptoms is faster than 1 hour and some have shown that the time to ﬁrst symptom improvement is within 30 minutes. One study even showed that 95% of patients have some response within 60 minutes of receiving C1-INH (Craig et al 2008). Laryngeal edema attacks seem to respond most rapidly to treatment followed by abdominal, then facial and peripheral attacks. Shorter times from the onset of symptoms to the infusion of C1-INH (especially within 2 hours) seem to be associated with faster and more effective improvement of symptoms. One of the drawbacks of comparing these studies is that the criteria to determine which types of attacks to treat were not consistent from study to study. It seems reasonable to treat any attack causing a patient distress. Since HAE is a complex disease, predicting when a patient’s symptoms may become worse can be very difﬁcult. Several groups also demonstrated that C1-INH concen- trate infusions given regularly can prevent acute attacks. 980 The intervals at which C1-INH concentrate is given for prophylaxis can vary considerably, with one study dem- onstrating a reduction in acute attacks with infusion every 3 days (Waytes et al 1996), and another study demonstrating a reduction in attacks with infusions every 5–7 days (Levi et al 2006). It is interesting that the half-life of C1-INH has been reported to be from 36 to 48 hours (Bernstein 2008), so one might think that infusions given every 5–7 days would not be adequate. However, the study by Levi et al (2006) does indeed demonstrate improvement in symptoms with this interval, suggesting that even increasing C1-INH levels slightly can result in signiﬁcant reduction of HAE attacks. This is consistent with the observations that C4 levels peak several hours after C1-INH levels and remain elevated for a longer period of time, demonstrating a biochemical effect that exceeds the serum half-life of C1-INH levels. However, the actual frequency of C1-INH infusions should probably be tailored on an individual basis, attempting to eliminate acute attacks with the lowest necessary frequency of C1-INH treat- ment. The data from these studies support the use of C1-INH concentrate for long-term prophylaxis for either patients that continue to have attacks despite prophylactic therapy with agents like attenuated androgens, or for patients with unwanted side effects related to androgen treatment. Several authors have demonstrated home therapy as a potential option for patients with HAE. Levi et al (2006), as mentioned previously, demonstrated a signiﬁcant reduc- tion in attack frequency in patients with scheduled C1-INH concentrate self-infusions at home. They also demonstrated faster treatment and improvement of acute attacks when patients were able to treat themselves at home. Patients in their study were successful in self-administering an intrave- nous catheter and infusion at home in 98% of cases. Initiating home therapy would require a signiﬁcant amount of patient education on safely administering infusions. Patients should also be educated on symptoms that would require immediate medical attention. Certainly, in a case of laryngeal edema, a patient should ﬁrst call their emergency number before attempting a home infusion. In cases of abdominal attacks, patients should call their physician or report to the hospital if their symptoms are at all different from typical attacks or if they are not resolving with therapy. Patients with HAE can certainly develop other abdominal conditions that may present similarly. These studies demonstrate that if done in the appropriate environment with adequate education and patient understanding, home C1-INH concentrate infusion for prophylaxis or acute treatment is a promising therapy leading to signiﬁcant improvement of quality of life, faster Therapeutics and Clinical Risk Management 2008:4(5)