The Buzz by HIVE, Issue #8, October 2021
Issue #8, October 2021

The Buzz returns with Issue #8, featuring the new international urticaria guidelines, a trial of convalescent plasma in COVID-19, and new publications on peanut immunotherapy, food allergy desensitization, and combination treatment for allergic rhinitis. View archived issues of The Buzz at thehivecommunity.org/the-buzz.

 

Updated guidelines for chronic urticaria

Following a consensus conference held last December, the updated international urticaria guidelines are now in press and endorsed by 50 participating national and international medical and scientific societies.

The updated guidelines include expert recommendations and suggestions on defining, classifying, and diagnosing chronic spontaneous and inducible urticaria. The section on management notes treatment goals should include complete control and a normal quality of life. Pharmacologic treatment should be continuous, until no longer needed due to spontaneous remission. Second-generation H1-antihistamines are recommended as daily treatment in the first-line setting, with up-dosing as high as four times standard dose as needed. Omalizumab, the only other approved agent for chronic urticaria, is recommended for patients without sufficient benefit to antihistamines. Patients with severe disease refractory to antihistamine and omalizumab combinations can be offered cyclosporin. Relatively high doses of steroids are needed for urticaria, and therefore are not generally recommended outside of specialist clinics or as a short course to bring acute disease under control.

Read more: [Sosido Link] Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The International EAACI/GA²LEN/EuroGuiDerm/APAAACI Guideline for the Definition, Classification, Diagnosis and Management of Urticaria [published online ahead of print, 2021 Sep 18]. Allergy. 2021;10.1111/all.15090. doi:10.1111/all.15090

 

The CONCOR-1 study of convalescent plasma for COVID-19 treatment

The results of the international CONCOR-1 study of convalescent plasma for COVID-19 are now published in Nature Medicine. In this study, patients receiving oxygen for COVID-19 were randomized 2:1 to receive 500mL of convalescent plasma or standard care. The primary endpoint was intubation or death within 30 days. The trial was halted for futility at the planned interim analysis, at 78% of planned enrollment. Intubation or death occurred in 32.4% of patients receiving plasma compared with 28% of patients receiving standard of care (relative risk = 1.16; 95% CI, 0.94-1.43, p=0.18). These results are generally consistent with other studies of convalescent plasma for COVID-19 treatment.

The CONCOR-1 study included detailed analysis of the blood products used in the trial from four different suppliers, with four serologic markers evaluated. In the subgroup analysis, the efficacy point estimate for Supplier 1 non-significantly favoured plasma treatment, while the others favoured standard of care. In a multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of convalescent plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05).

Read more: [Sosido Link] Bégin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial [published online ahead of print, 2021 Sep 9]. Nat Med. 2021;10.1038/s41591-021-01488-2. doi:10.1038/s41591-021-01488-2

 

Post-hoc analysis of allergic reaction severity from a peanut immunotherapy study

Bégin and colleagues conducted a post-hoc analysis of the PEPITES peanut immunotherapy study. The original study was a double-blind, placebo-controlled food challenge study using the ViaskinTM Peanut 250ug patch, which contains 250ug of peanut protein, to desensitize children aged 4-11 years old. The study demonstrated statistically significant superiority compared to placebo in desensitizing after 12 months of therapy.

The current analysis aimed to evaluation the role of the ViaskinTM patch on reducing the severity of allergic reactions, an important caregiver-stated treatment goal. At baseline, the proportion of patients with mild, moderate, or severe objective signs and symptoms for assessable organ systems was similar between groups. At month 12, the proportion of patients with maximum symptom severity of “none” or “mild” was lower in the treated group compared to placebo (31.1% vs 16.5%). Those with a maximum score of “severe” were also lower in the treated compared with placebo (16.2% vs 27.5%; p=0.019). The proportion of subjects with maximum severity scores of “severe” remained lower in the treated patients regardless of whether their eliciting dose increased, decreased, or was unchanged.

Read more: [Sosido Link] Bégin P, Bird JA, Spergel JM, et al. Reduction in peanut reaction severity during oral challenge after 12 months of epicutaneous immunotherapy [published online ahead of print, 2021 Sep 7]. Allergy. 2021;10.1111/all.15083. doi:10.1111/all.15083

 

Dupilumab and subcutaneous immunotherapy for allergic rhinitis

Corren and colleagues conducted a multicentre proof-of-concept trial to evaluate if timothy grass-specific subcutaneous immunotherapy (SCIT) combined with dupilumab treatment would enhance efficacy and improve tolerance of the SCIT. The study randomized 103 patients 1:1:1:1 to receive SCIT alone, dupilumab alone, combination treatment, or placebo. SCIT was delivered as an 8-week cluster protocol followed by 8 weeks of maintenance, while dupilumab was dosed 300mg every 2 weeks.

The primary endpoint was change in total nasal symptom score (TNSS) from baseline to week 17 following nasal allergen challenge. The addition of dupilumab to SCIT did not significantly improve this endpoint (least squares mean -56.76% vs -52.03%, p=0.7851). There was a higher proportion of combination therapy patients achieving maintenance dose compared to SCIT alone, and fewer required epinephrine rescue treatment or withdrew from the study for tolerability concerns. The study also reports on several biomarkers of interest. The authors note that nasal antigen challenge may not be the best method to test for efficacy of dupilumab.

Read more: [Sosido Link] Corren J, Saini SS, Gagnon R, et al. Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial. J Asthma Allergy. 2021;14:1045-1063. Published 2021 Aug 16. doi:10.2147/JAA.S318892

 

Future strategies in food allergy desensitization

A new review on strategies to manage food allergy from Bruton and colleagues looks at the emerging evidence for peanut oral immunotherapy (OIT), and what the future may hold. They discuss the data supporting desensitization, as well as the lack of evidence on how long the effects last after cessation of OIT. Similarly, the safety of OIT is reasonably well studied during the induction and initial maintenance phase, but questions remain on the long-term safety. Better mechanistic understanding of food allergy is needed to allow for targeted desensitization.

Of the possible future strategies discussed, the authors note that although CAR-T therapy could theoretically be adopted for food allergy, the side effect profile would need to greatly improve to achieve a reasonable benefit-risk profile for non-cancer patients. More likely in the near term would be direct targeting signalling pathways implicated in allergy, including IL-4, IL-5, IL-9, and IL-13. Characterizing the tissue localization of allergen-specific memory lymphocytes may also reveal reservoirs of IgE responses.

Read more: [Sosido Link] Bruton K, Spill P, Chu DK, Waserman S, Jordana M. Peanut allergy: Beyond the oral immunotherapy plateau. Clin Transl Allergy. 2021;11(6):e12046. Published 2021 Aug 13. doi:10.1002/clt2.12046

 

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