Issue #14, June 2022
We are pleased to bring you Issue 14 of The Buzz! In this month’s issue, we highlight a possible new predictive biomarker for severe anaphylaxis in children, the use of direct oral challenge to de-label penicillin allergy during pregnancy, and three publications in atopic dermatitis: new data with the JAK1-selective inhibitor abrocitinib, a structured appraisal of the clinical practice guidelines, and a metaanalysis of the literature on the use of dilute bleach baths. View archived issues of The Buzz at thehivecommunity.org/the-buzz.
PAF-AH as a biomarker for severe anaphylaxis in children
Though anaphylaxis occurs in up to 2% of children, there are currently no reliable blood tests to predict the occurrence of anaphylaxis, the severity of reaction, or the future risk of severity. A biomarker that can be tested outside of an acute anaphylactic event is needed. Upton and colleagues evaluated plateletactivating factor acetylhydrolase (PAF-AH) for its appropriateness as possible predictive biomarker. They conducted a prospective observational study of patients presenting to the emergency department or the in-patient allergy service at SickKids from 2015 to 2019. A total of 46 children met the criteria for study, of which 34 (74%) had mild-moderate anaphylaxis and 12 (26%) had severe anaphylaxis. Biomarkers were measured at presentation and at a follow-up visit at least 4 weeks later.
Nine of 12 children with severe anaphylaxis had reduced PAF-AH activity compared with 14/34 with mild-moderate anaphylaxis (p < .05). All three of the children who required ICU admission had markedly reduced mean PAF-AH compared to 20/23 who required ward/emergency department care (p < .05). PAF-AH during acute anaphylaxis was unchanged compared to levels measured at follow-up and were lower than healthy pediatric controls (p < .05), indicating that this biomarker could be used outside of an acute event. Elevated tryptase was present in 15/46 (33%) children during anaphylaxis, though this was not correlated with anaphylaxis severity (p = .135).
Read more: [Sosido link] Upton JEM, Hoang JA, Leon-Ponte M, et al. Platelet-activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children [published online ahead of print, 2022 Apr 9]. Allergy. 2022;10.1111/all.15308. doi:10.1111/all.15308
Using direct oral challenge to de-label penicillin allergy during pregnancy
In non-pregnant, low risk patients previously labelled as having penicillin allergy, direct oral challenge (DOC) without prior skin testing has good safety data. Mak and colleagues conducted a study to evaluate DOC in low-risk, third trimester pregnant patients at the BC Women’s Hospital and Health Centre. Risk was assessed using the PEN-FAST point-of-care decision tool. Patients received a 500 mg oral dose of amoxicillin and were observed for one hour. If there was no evidence of IgE reaction, patients were discharged with instructions of when to call the clinic for possible delayed reaction. In total, 245 patients were enrolled, with 216 deemed low risk and 207 undergoing DOC.
Most patients reported their last reaction to penicillin over 10 years ago (77%), primarily consisting of maculopapular rash lasting less than 24 hours. Two hundred and three (98%) reported no immediate or delayed hypersensitivity to the DOC. Only 2% reported delayed maculopapular rashes which were
treated with topical betamethasone valerate and oral antihistamines. Following DOC, 90% of patients were not worried about penicillin reactions and 84% stated they would be comfortable taking penicillin in the future.
Read more: [Sosido link] Mak R, Zhang BY, Paquette V, et al. Safety of Direct Oral Challenge to Amoxicillin in Pregnant Patients at a Canadian Tertiary Hospital [published online ahead of print, 2022 Apr 7]. J Allergy Clin Immunol Pract. 2022;S2213-2198(22)00337-3. doi:10.1016/j.jaip.2022.03.025
Association between higher efficacy thresholds and better quality of life scores with abrocitinib treatment
Abrocitinib is an oral, selective JAK1 inhibitor, approved for moderate-to-severe atopic dermatitis (AD) in several countries and under review with Health Canada as of May 2022. The primary analysis of the phase 3 monotherapy trials was published in 2020, and now Ständer and colleagues have conducted a post-hoc pooled analysis of the data to evaluate if higher efficacy thresholds are associated with additional quality of life improvements. This analysis evaluated patients who reached Eczema Area and Severity Index (EASI)-90 to EASI100 and those reaching Peak Pruritus Numerical rating scale (PP-NRS)0/1. Data were pooled from the two JADE MONO phase 3 studies as well as the Phase 2b study. A total of 942 patients receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo were included.
More abrocitinib-treated patients achieved commonly used or higher threshold efficacy end points at week 12 compared to placebo. For instance, at the EASI-90 to <EASI-100 threshold, the proportions were 29% (200mg abrocitinib), 16% (100mg abrocitinib), and 6% (placebo). The proportion of patients reporting no effect of their AD on quality of life (by Children’s Dermatology Life Quality Index / Dermatology Life Quality Index (CDLQI/DLQI)) was higher in patients who achieved higher efficacy thresholds. For those achieving EASI-100, the proportion reporting “no effect” on quality of life was 2.34 times higher than those achieving EASI-75 to <EASI-90. Odds ratios for the associations were not presented within the publication. The authors conclude that abrocitinib-treated patients achieving higher efficacy thresholds realize additional quality of life benefits.
Read more: [Sosido link] Ständer S, Bhatia N, Gooderham MJ, et al. High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents [published online ahead of print, 2022 Apr 24]. J Eur Acad Dermatol Venereol. 2022;10.1111/jdv.18170. doi:10.1111/jdv.18170
Appraisal of atopic dermatitis clinical practice guidelines according to AGREE-II
Ghazal and colleague aimed to appraise the quality of clinical practice guidelines for adult AD against the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria, and to map the incorporation of dupilumab compared to conventional systemic therapy (CST). A systematic literature search was undertaken in 2020 and retrieved 12 clinical practice guidelines. AGREE-II evaluates guidelines according to six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence.
AGREE-II median scores by domain were: scope/purpose, 78%; stakeholder involvement, 54%; rigor of development, 39%; clarity of presentation, 85%; applicability, 27%; and editorial independence, 76%. Gaps were found in mechanisms for updates, facilitators/barriers, resource implications, and stakeholder involvement. The incorporation of dupilumab was highly variable across the CPGs, with recommendations ranging from second line preferred over nbUVB or CST to fourth-line after nbUVB and CST. The authors suggest that incorporating quality criteria into guideline development would reduce the variability in recommendations.
Read more: [Sosido link] Ghazal S, Ridha Z, D'Aguanno K, et al. Treatment Guidelines for Atopic Dermatitis Since the Approval of Dupilumab: A Systematic Review and Quality Appraisal Using AGREEII. Front Med (Lausanne). 2022;9:821871. Published 2022 Mar 9. doi:10.3389/fmed.2022.821871
Systematic review and meta-analysis of dilute bleach baths for atopic dermatitis
The American College and American Academy of Allergy, Asthma & Immunology commissioned a systematic review and meta-analysis of the use of bleach bathing in AD to inform upcoming clinical guidelines. Bathing two to three times per week for 10 minutes in a dilute bleach solution (approximately 0.005%) is sometimes recommended to reduce the presence of S. aureus on the skin. Studies were included if they randomized bleach baths to no bleach baths for patients with AD. There were 10 studies included in the analysis comprising 307 patients with mild-to-severe AD at baseline. The mean of mean EASI across studies was 23.38, the median of mean age was 7.2 years, and half of patients were female.
Bleach baths probably improve AD severity with moderate certainty (22% vs 32% improved EASI by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]) and may slightly reduce skin S aureus colonization with low certainty (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]). Adverse events, including dry skin, irritation, itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. The findings demonstrate that about one in ten patients may somewhat improve, and there is a need for controlled clinical trials in this area.
Read more: [Sosido link] Bakaa L, Pernica JM, Couban RJ, et al. Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE [published online ahead of print, 2022 Mar 30]. Ann Allergy Asthma Immunol. 2022;S1081-1206(22)00286-1. doi:10.1016/j.anai.2022.03.024
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