Bibliographic updates

March 2017

Claude Molina et Jacques Gayraud

1.    Hereditary Angioedema Prophtlaxis: Kallicrein inhibition by Lanadelumab
2.    Anti-Interleukin 31 Receptor A, Nemolizumab for Atopic Dermatitis in Adults
3.    Hypersensitivity to Aspirin and NSAID and Coronary artery disease
4.    Predictors of adverse effects on Oral Immunotherapy (OIT) for Peanut Allergy
5.    Omalizumab facilitates rapid OIT for Peanut allergy

I.    Hereditary Angioedema Prophylaxis:
Kallicrein Inhibition by Lanadelumab (L)
A.Banerji et al NEJM 2017 376  717-728 (27 Febr)   

L. is a new recombinant fully human monoclonal antibody allowing sustained inhibition of kallicrein, implicated in bradykinin mediated angioedema and increased local capillary permeability. It has been tested in a phase 1 b multicenter double blind placebo controlled trial (24 patients & 13 Placebo assigned in sequential dose groups : 30mg, 100mg 300mg 400mg) in 2 administrations 14 days apart. Efficacy was assessed by the rate of attacks: 8 to 50 days) and measurement of plasma levels of cleaved HMW of kininogen.
At a dose of 300 and 400mg L reduced kininogen to levels approaching that from normal patients and the 300mg and 400 mg groups had 100% and 88% fewer attacks respectively than the placebo groups. The usefulness of this drug, without significant adverse effects may complete other prophylactic options like C1 Inhibitor (Cinryze) (┬«) and attenuated androgens  such Danazol┬«.
PS: A new C1 inhibitor, CSL830,  a nanofiltered preparation suitable for subcutaneous injection and self-administration has been recently and successfully tested in a phase 3 trial on 90 patients (H.Longhurst and al NEJM 2017 March 231131-1140).

II.    Anti-Interleukin 31 Receptor A, Nemolizumab (N)
for Atopic Dermatitis in Adults (AD)  
T. Ruzika et al NEJM 2 Mars 2017 376 826-835                

IL-31plays a role in the pathogenesis of AD and more specifically on the occurrence of pruritus. In order to assess the efficacy and safety of N a humanized antibody against IL 31 receptor A, a phase 2, multicenter randomized d.b.p.c 12 weeks trial, was assigned to 264 patients (18 to 65 years of age ) at subcutaneous dose of 0.1, 0.5 or 2mg/kg of body weight every 8 weeks;  the primary end point being percentage improvement of the score of pruritus and secondary end-point changes in body surface area of AD.         
At all doses, N significantly (30%) and rapidly decreased  pruritus. Possible improvement of other symptoms: sleep, quality of life, cutaneous score, is suggested but without statistical comparisons. In spite of the limited length of this trial, this new therapy should be included as a part of a comprehensive approach of different phenotypes of AD and nearby Dupilumab: anti IL 4 and IL 13, already recently studied.

III.    Hypersensitivity (H) to Aspirin and NSAID and Coronary artery disease : Model of collaboration between allergists and cardiologists
G.Cortelli et al : Allergy 2017  72  498-506         

Aspirin (A) is mandatory for patients who need a coronary angiography possibly followed by stenting and may also require dual antiplatelet therapy for 6 to 12 months. In subjects at risk of H. the physicians have to choose between challenge and desensitization. This European multicenter study (10 centers and 310 patients) aimed to establish criteria for eligibility for an A challenge, and ensure the best therapy.
217 subjects had histories of H. 119 at a dose lower than 300mg.
163 underwent challenge, 147desensitization.                         
At the end of this study, the recommendations are as follows: in patients with stable coronary disease and history of non -severe H to A /NSAID a challenge is advisable. Patients with acute coronary disease, especially following doses lower than 100mg should directly undergo desensitization.
IV.    Predictors of adverse effects on Oral Immunotherapy (OIT) for Peanut Allergy
Y.V.Virkud et al JACI  March 2017 139 3 882-888              

3 studies recruited 104 children assigned to OIT for peanut allergy:
Increased rates of systemic reactions (42% of subjects) and gastro-intestinal side effects, were observed likely related to dosing.                       
Higher rates of these adverse effects were associated with larger skin prick test wheal size (related to gastro-intestinal symptoms) or allergic rhinitis or asthma (predictors of systemic reactions).                        
Even graded mild, and declining over time, these adverse reactions need further studies to establish the risks/benefits of OIT for peanut allergy in children

V.    Omalizumab (O)  facilitates rapid OIT for Peanut allergy
A.J.Mac Ginnitie et al JACI March 2017  3  139 873-881      

Adjunction of O to OIT for peanut allergy allows more rapid up-dosing and decreases adverse effects. This is the result of a short trial on 37 subjects randomized to O (29) or  placebo (8) .                                                                        
O-children treated tolerated higher doses of peanut that the placebo group on initial desensitization day and throughout the study.               
23 of 27 O tolerated 2000mg (about 8 peanuts) six weeks after stopping the treatment.    
16 of 27 tolerated 4000mg of peanut 33 weeks after stopping               
Over all significant reactions occurred on 6 of 8 subjects placebo compared to 4 of 27 O.

Your comments and questions are welcome at the following addresses:

Claude Molina                         
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Jacques Gayraud
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Last updated 16 May 2017