Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal.

Background Peanut oral immunotherapy (OIT) is a promising approach to peanut allergy but reactions are frequent and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair) may allow more rapid peanut updosing and decrease reactions. Objective To evaluate if omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n=29) or placebo (n=8). After 12 weeks of treatment subjects underwent a rapid one-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued and subjects continued on 2000 mg of peanut protein. They underwent an open challenge to 4000 mg peanut protein twelve weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab versus 22.5 mg for placebo treated subject. Subsequently 23 of 29 (79%) subjects randomized to omalizumab tolerated 2000 mg peanut protein 6 weeks after stopping omalizumab versus 1 of 8 (12%) receiving placebo (p<0.01). Twenty-three subjects on omalizumab versus 1 on placebo passed the 4000 mg food challenge. Overall reaction rates were not significantly lower in omalizumab versus placebo treated subjects (OR=0.57 p=0.15), although omalizumab treated subjects were exposed to much higher doses of peanut. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut OIT. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

In this study, AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults.