Background Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; ...Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective We sought to evaluate whether 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 1-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. Subjects underwent an open challenge to 4000 mg of peanut protein 12 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-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo ( P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. 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.
Rationale AR101, a pharmaceutical-grade peanut protein formulation, was well tolerated and demonstrated robust activity in a Phase 2, double-blind, placebo-controlled trial in 4-21 year olds.
Methods In ARC002, former ARC001 placebo subjects up-dosed to 300 mg/d of peanut protein as AR101, then underwent double-blind placebo-controlled food challenge (DBPCFC) after 2 more weeks of therapy.
The American Academy of Pediatrics and US Centers for Disease Control and Prevention4,5 recommend not vaccinating children with severe egg allergy, which is defined by the American Academy of ...Pediatrics as a history of hives, angioedema, allergic asthma, or anaphylaxis. Age (y) Sex Asthma Other food allergies Previous egg reaction SPT egg IgE egg (kUA/L) Eats egg Total IgE (kUA/L) Reaction and timing Dose 1 Male No Peanut Vomiting Not done 7.02 Baked goods Not done Small area of erythema with papule at diaper line, resolved with observation 90% Seasonal 1 Male No Milk Hives 3-mm Wheal/5-mm flare 1.28 Baked goods 25 Multiple hives on chest, given diphenhydramine with resolution Simultaneous administration of 10% H1N1 and 10% seasonal 6 Female No None Hives, vomiting Not done >100 None >2000 Large local erythema, resolved with observation. 10% H1N1 3 Male No Peanut, tree nut, milk None Not done 6.26 Baked goods 1099 Single prominent hive, resolved with diphenhydramine 10% Seasonal Table I Demographics and reaction details for patients experiencing an allergic reaction to the influenza vaccine
Background Atopic dermatitis (AD) is characterized by local and systemic TH 2 responses to cutaneously introduced allergens and is a risk factor for asthma. Blockade of TH 2 cytokines has been ...suggested as therapy for AD. Objectives We sought to examine the effect of the absence of IL-4 and IL-13 on the TH 17 response to epicutaneous sensitization in a murine model of allergic skin inflammation with features of AD. Methods Wild-type, IL4 knockout (KO), IL13 KO and IL4/13 double KO (DKO) mice were subjected to epicutaneous sensitization with ovalbumin (OVA) or saline and airway challenged with OVA. Systemic immune responses to OVA, skin and airway inflammation, and airway hyperresponsiveness were examined. Results OVA-sensitized DKO mice exhibited impaired TH 2-driven responses with undetectable OVA-specific IgE levels and severely diminished eosinophil infiltration at sensitized skin sites but intact dermal infiltration with CD4+ cells. DKO mice mounted exaggerated IL-17A but normal IFN-γ and IL-5 systemic responses. Airway challenge of these mice with OVA caused marked upregulation of IL-17 mRNA expression in the lungs, increased neutrophilia in bronchoalveolar lavage fluid, airway inflammation characterized by mononuclear cell infiltration with no detectable eosinophils, and bronchial hyperresponsiveness to methacholine that were reversed by IL-17 blockade. IL-4, but not IL-13, was identified as the major TH 2 cytokine that downregulates the IL-17 response in epicutaneously sensitized mice. Conclusion Epicutaneous sensitization in the absence of IL-4/IL-13 induces an exaggerated TH 17 response systemically and in lungs after antigen challenge that results in airway inflammation and airway hyperresponsiveness.
Ecallantide is a human plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema for patients 12 years of age and older. Ecallantide is produced in Pichia pastoris ...yeast cells by recombinant DNA technology. Use of ecallantide has been associated with a risk of hypersensitivity reactions, including anaphylaxis.
The objective of this detailed retrospective data review was to characterize anaphylaxis cases within the ecallantide clinical trials database.
Potential cases of hypersensitivity reactions in the ecallantide clinical development program were identified by examining reported adverse events. The National Institute of Allergy and Infectious Disease criteria were used to identify those events that were consistent with anaphylaxis; these cases were then reviewed in detail. Results from investigational antibody testing also were examined.
Among patients who received subcutaneous ecallantide (n = 230 patients; 1045 doses of 30 mg ecallantide), 8 patients (3.5%) had reactions that met the National Institute of Allergy and Infectious Disease criteria for anaphylaxis; none occurred on first exposure to the drug. All 8 reactions had symptom onset within 1 hour of exposure and cutaneous manifestations commonly observed in type I hypersensitivity reactions. All the reactions responded to standard management of type I hypersensitivity reactions and resolved without fatal outcomes. IgE antibody testing to ecallantide or P pastoris was not consistently positive in patients who experienced apparent type I hypersensitivity reactions.
Anaphylaxis episodes after subcutaneous ecallantide exposure have clinical features suggestive of type I hypersensitivity reactions. However, anti-ecallantide or anti–P pastoris IgE antibody status was not found to be reliably associated with anaphylaxis.
Participants completed validated measures of food allergy-related QoL and perceived risk of negative food allergy outcomes at baseline and study conclusion (week 52), and an interview about peanut ...consumption at week 52.
Conclusions By setting and continually refining ssIgE and skin prick test recommendations using the SCAMP method, allergists can better determine the risk of severe reactions and triage patients to ...the appropriate resource setting for an OFC.
Rationale Peanut oral immunotherapy (OIT) is a promising approach to peanut allergy but reactions frequently occur and some patients cannot be desensitized.
Hereditary angioedema (HAE) is a rare disorder associated with episodic attacks of well-demarcated angioedema. Attacks that affect the larynx can result in life-threatening airway obstruction.
To ...examine efficacy and safety of ecallantide treatment for laryngeal HAE attacks.
Data were combined from 4 clinical studies (EDEMA2, EDEMA3, EDEMA4, and DX-88/19) evaluating 30 mg of subcutaneous ecallantide for treatment of acute HAE attacks. Efficacy was assessed using 2 validated, HAE-specific, patient-reported outcome measures. The change in Mean Symptom Complex Severity (MSCS) score indicates change in symptom severity; a negative score indicates improvement. The calculated minimally important difference (MID) for change in severity is -0.30. The Treatment Outcome Score (TOS) measures treatment response. A positive score indicates improvement; the calculated MID is 30.
Overall, 98 patients received ecallantide for 220 laryngeal attacks. The mean ± SD change in MSCS score was -1.1 ± 0.73 and -1.6 ± 0.68 at 4 and 24 hours, respectively. The mean ± SD TOS was 73.5 ± 35.8 and 85.5 ± 27.8 at 4 and 24 hours, respectively. Median time to significant improvement was 185 minutes (95% confidence interval, 167-226). One attack required intubation. Four treatment-emergent serious adverse events were reported, including 2 HAE attacks that resulted in hospitalization and 2 anaphylactic reactions. One of these reactions required treatment with epinephrine, but both patients recovered fully. There were no deaths.
In this large attack series, ecallantide was effective for treatment of laryngeal HAE attacks. There is a risk of hypersensitivity, including anaphylaxis, consistent with product labeling. As such, ecallantide should be administered under the supervision of a health care professional.
clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before implementation of registration requirements); NCT00262080 for EDEMA3, NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19.
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