Publications by authors named "Philippe Bégin"

68 Publications

Potential efficacy of high-dose inhaled salbutamol for the treatment of abdominal pain during oral food challenge.

J Allergy Clin Immunol Pract 2021 Apr 5. Epub 2021 Apr 5.

Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada; Department of Medicine, Section of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada,. Electronic address:

Background: Abdominal pain is a frequent symptom of IgE-mediated food allergy with limited therapeutic options. Visceral smooth muscle cell relaxation can be induced through beta-adrenergic stimulation.

Objective: To evaluate the efficacy of inhaled salbutamol empirically used to relieve abdominal pain caused by IgE-mediated allergic reactions at one center.

Methods: All double-blind placebo-controlled food challenges to peanut performed at on center between 2016 and 2021 were reviewed to identify patients that presented abdominal pain as part of their reaction. The primary outcome measure was the delay between the initiation of therapy and improvement of abdominal pain. It was compared between patients that had received inhaled salbutamol as part of their treatment and those that did not. Cox regression was performed to control for potential confounders.

Results: During the study period, 186 positive DBPCFCs were performed, including 126 for peanut allergy. Of these, 77 were treated for abdominal pain and 57 met the criteria for inclusion in the study. Patients that received salbutamol improved significantly faster (median 12.5 minutes) than those that did not (median 65 minutes) (χ=45; p<0.0001). In Cox regression, the administration of salbutamol and emesis were found to increase the rate of improvement by a hazard ratio of 11.35 (95%CI: 5.40-23.9; p<0.0005).

Conclusion: This retrospective study provides hypothesis-generating evidence for the use of salbutamol in the treatment of IgE-mediated abdominal pain. Further investigation in a double-blind randomized controlled trial is warranted.
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http://dx.doi.org/10.1016/j.jaip.2021.03.040DOI Listing
April 2021

Practical challenges in oral immunotherapy resolved through patient-centered care.

Allergy Asthma Clin Immunol 2021 Mar 18;17(1):31. Epub 2021 Mar 18.

Allergy and Immunology, Centre Hospitalier de L'Université de Montréal, Hôpital Notre-Dame, Montreal, QC, Canada.

Oral immunotherapy (OIT) is now widely recognized as a valid option for the management of IgE-mediated food allergies. However, in real-life practice, OIT can lead to a variety of unique situations where the best course of action is undetermined. In patient-centered care, individual patient preferences, needs and values, should guide all clinical decisions. This can be achieved by using shared-decision making and treatment customization to navigate areas of uncertainty in a way that is responsive to patient's needs and preferences. However, in the context of OIT, lack of awareness of potential protocol adaptability or alternatives can become a barrier to treatment personalization. The purpose of this article is to review the theoretical bases of patient-centered care and shared decision-making and their practical implication for the patient-centered delivery of OIT. Clinical cases highlighting common challenges in real-life OIT practice are presented along with a discussion of potential personalized management options to be considered. While the practice of OIT is bound to evolve as additional scientific and experiential knowledge is gained, it should always remain rooted in the general principles of patient-centered care.
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http://dx.doi.org/10.1186/s13223-021-00533-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971360PMC
March 2021

An Approach to the Office-Based Practice of Food Oral Immunotherapy.

J Allergy Clin Immunol Pract 2021 Mar 5. Epub 2021 Mar 5.

Geisel School of Medicine at Dartmouth, Hanover, NH; Dartmouth-Hitchcock Medical Center, Lebanon, NH. Electronic address:

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes.
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http://dx.doi.org/10.1016/j.jaip.2021.02.046DOI Listing
March 2021

Community Use of Epinephrine for the Treatment of Anaphylaxis: A Review and Meta-Analysis.

J Allergy Clin Immunol Pract 2021 Feb 4. Epub 2021 Feb 4.

Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Center, Montreal, QC, Canada.

Background: Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre-hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines.

Objectives: A search was conducted on PubMed and Embase in April 2020. Our systematic review focused on 4 domains: (1) epinephrine use in the pre-hospital setting; (2) barriers to epinephrine use in the pre-hospital setting; (3) cost evaluation and cost-effectiveness of epinephrine use; and (4) programs and strategies to improve epinephrine use during anaphylaxis.

Methods: Two meta-analyses with logit transformation were conducted to: (1) calculate the pooled estimate of the rate of epinephrine use in the pre-hospital setting among cases of anaphylaxis and (2) calculate the pooled estimate of the rate of biphasic reactions among all cases of anaphylaxis.

Results: Epinephrine use in the pre-hospital setting was significantly higher for children compared with adults (20.98% [95% confidence interval (CI): 16.38%, 26.46%] vs 7.17% [95% CI: 2.71%, 17.63%], respectively, P = .0027). The pooled estimate of biphasic reactions among all anaphylaxis cases was 3.92% (95% CI: 2.88%, 5.32%). Our main findings indicate that pre-hospital use of epinephrine in anaphylaxis remains suboptimal. Major barriers to the use of epinephrine were identified as low prescription rates of epinephrine autoinjectors and lack of stock epinephrine in schools, which was determined to be cost-effective. Finally, in reviewing programs and strategies, numerous studies have engineered effective methods to promote adequate and timely use of epinephrine.

Conclusion: The main findings of our study demonstrated that across the globe, prompt epinephrine use in cases of anaphylaxis remains suboptimal. For practical recommendations, we would suggest considering stock epinephrine in schools and food courts to increase the use of epinephrine in the community. We recommend use of pamphlets in public areas (ie, malls, food courts, etc.) to assist in recognizing anaphylaxis and after that with prompt epinephrine administration, to avoid the rare risk of fatality in anaphylaxis cases.
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http://dx.doi.org/10.1016/j.jaip.2021.01.038DOI Listing
February 2021

Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset.

bioRxiv 2021 Jan 25. Epub 2021 Jan 25.

Functional and lasting immune responses to the novel coronavirus (SARS-CoV-2) are currently under intense investigation as antibody titers in plasma have been shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we sought to determine the presence of SARS-CoV-2-specific memory B cells in COVID-19 convalescent patients. In this study, we report on the evolution of the overall humoral immune responses on 101 blood samples obtained from 32 COVID-19 convalescent patients between 16 and 233 days post-symptom onset. Our observations indicate that anti-Spike and anti-RBD IgM in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity in convalescent plasma declines rapidly compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which increase over time, and the number of IgG+ memory B cells which remain stable thereafter for up to 8 months after symptoms onset. With the recent approval of highly effective vaccines for COVID-19, data on the persistence of immune responses are of central importance. Even though overall circulating SARS-CoV-2 Spike-specific antibodies contract over time during convalescence, we demonstrate that RBD-specific B cells increase and persist up to 8 months post symptom onset. We also observe modest increases in RBD-specific IgG+ memory B cells and importantly, detectable IgG and sustained Fc-effector activity in plasma over the 8-month period. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for the prevention of secondary infections, vaccine efficacy and herd immunity against COVID-19.
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http://dx.doi.org/10.1101/2021.01.25.428097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852267PMC
January 2021

A High Proportion of Canadian Allergists Offer Oral Immunotherapy but Barriers Remain.

J Allergy Clin Immunol Pract 2020 Dec 29. Epub 2020 Dec 29.

Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, CHU Sainte-Justine, Montréal, QC, Canada.

Background: Limited data on clinical implementation of oral immunotherapy (OIT) have been reported with incomplete evaluation of barriers.

Objective: To survey Canadian allergists on their current practice of OIT and barriers to implementation and expansion of OIT.

Methods: A survey investigating current practice and logistical and clinical barriers to offering or expanding OIT was distributed to all Canadian Society of Allergy and Clinical Immunology allergists.

Results: Of 90 responding allergists, 52.2% reported offering OIT, most commonly to peanut. Food sublingual immunotherapy was offered by 7% of allergists. Having received training for OIT was associated with currently performing OIT (P = .008); 44.7% of allergists offering OIT had received training on OIT, and 81.4% not offering OIT had no training. A total of 87% of allergists performing OIT reported lack of efficacy data and lack of support staff and clinic space, and concerns about increased oral challenges (84%) were "moderately" to "extremely" important barriers to expanding OIT. For clinicians not offering OIT, concerns about safety (95%), after-hours support (95%), efficacy (93%), medicolegal risk (93%), and long-term practice implications (93%) were prioritized as significant barriers. Qualitative assessment suggested concerns about the practical challenges associated with OIT, the need for increased safety and efficacy data, and a desire for OIT guidelines and training.

Conclusion: The implementation of OIT faces many barriers, both clinical and logistical. Increasing high-quality safety and efficacy data may support those hesitant to offer OIT, and improving funding may address the practical infrastructure challenges. In addition, training will help expand access for allergists interested in performing OIT.
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http://dx.doi.org/10.1016/j.jaip.2020.12.025DOI Listing
December 2020

Treatment expectations in food-allergic patients referred for oral immunotherapy.

J Allergy Clin Immunol Pract 2020 Nov 26. Epub 2020 Nov 26.

Section of Allergy and Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Section of Allergy and Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.11.027DOI Listing
November 2020

Efficacité et innocuité du plasma de convalescent en cas de forme grave de COVID-19, extrapolée de données relatives à d’autres formes graves d’infections respiratoires virales : revue systématique et méta-analyse.

CMAJ 2020 Nov;192(47):E1559-E1570

Instituts indiens de santé publique de Delhi (N. Devasenapathy), Fondation de santé publique de l'Inde, Gurgaon, Haryana, Inde; Département des méthodes, des données et de l'incidence de la recherche en santé (Z. Ye, M. Loeb, F. Fang, B. Tadayon Najafabadi, Y. Xiao, R. Couban, G. Guyatt), Université McMaster, Hamilton, Ont.; Université de médecine chinoise de Guangzhou (F. Fang), Guangzhou, Guangdong, Chine; École de soins infirmiers de Chine occidentale et Hôpital de Chine occidentale (Y. Xiao), Université du Sichuan, Chengdu, Sichuan, Chine; Département de médecine (p. Bégin), Université de Montréal, Montréal, Qué.

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http://dx.doi.org/10.1503/cmaj.200642-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721266PMC
November 2020

Beta-2 Agonists May be Superior to Epinephrine to Relieve Severe Anaphylactic Uterine Contractions.

J Allergy Clin Immunol Pract 2021 Mar 9;9(3):1232-1241. Epub 2020 Nov 9.

Division of Allergy, Department of Medicine, Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada; Division of Allergy, Department of Pediatrics, Centre Hospitalier Universitaire Ste-Justine, Montreal, QC, Canada. Electronic address:

Background: Uterine contractions are recognized as a potential manifestation of anaphylaxis, but literature on their proper management is limited. It is widely recognized that anaphylactic reactions can cause uterine contractions, but little is known about their optimal management.

Objective: Review potential treatments for painful uterine contractions associated with anaphylaxis or mast cell activation.

Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed, Embase, and Cochrane were searched in English, French, and Spanish for reports of uterine anaphylaxis published up until July 2020. The search strategy used a combination of Boolean operators and included the following Medical Subject Heading terms and keywords: hypersensitivity; anaphylaxis; mastocytosis; uterus; uterine contraction; pelvic pain; labor, obstetric; labor, premature; and endometriosis.

Results: This systematic review identified 19 studies reporting on 31 cases of painful uterine contractions occurring during anaphylaxis or other events associated with mast cell activation. Nine patients were pregnant. We present 2 additional cases in nonpregnant women, one associated with an oral food challenge and the other associated with oral food desensitization. The most frequent triggers were subcutaneous immunotherapy (14 cases), food (6 cases), and drugs (4 cases). Uterine cramps were associated with systemic symptoms in 24 cases and lasted on average for 2.4 hours. Pretreatment with antihistamines and montelukast generally failed to prevent recurrence, but nonsteroidal anti-inflammatory drugs were used successfully in some reports. Response to intramuscular epinephrine was inconsistent. Data from ex vivo models indicate that epinephrine may paradoxically contribute to uterine contractions through alpha-receptor activity. A small number of cases showed good response to beta-2 agonists.

Conclusions: There is a lack of quality data on painful uterine contractions occurring in the context of anaphylactic reactions and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options.
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http://dx.doi.org/10.1016/j.jaip.2020.10.047DOI Listing
March 2021

Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals.

mBio 2020 10 16;11(5). Epub 2020 Oct 16.

Centre de Recherche du CHUM, Quebec, Canada

In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.
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http://dx.doi.org/10.1128/mBio.02590-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569150PMC
October 2020

Peanut consumption habits and incidence of new peanut allergy in a cohort of younger siblings of peanut-allergic children.

J Allergy Clin Immunol Pract 2021 Jan 1;9(1):539-541.e1. Epub 2020 Oct 1.

Pediatric Allergy and Clinical Immunology, CHU Sainte-Justine, Montreal, QC, Canada; Allergy and Clinical Immunology, Centre Hospitalier de l'Universite de Montreal (CHUM), Montreal, QC, Canada; Applied Clinical Research Unit, CHU Sainte-Justine, Montreal, QC, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.09.028DOI Listing
January 2021

Determinants of omalizumab dose-related efficacy in oral immunotherapy: Evidence from a cohort of 181 patients.

J Allergy Clin Immunol 2021 Jan 24;147(1):233-243. Epub 2020 Sep 24.

Department of Pediatrics, Section of Allergy and Clinical Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Department of Medicine, Section of Allergy and Clinical Immunology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; Department of Pediatrics, Hôpital de Chicoutimi, Saguenay, Québec, Canada. Electronic address:

Background: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown.

Objective: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT.

Methods: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented.

Results: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001).

Conclusion: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.
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http://dx.doi.org/10.1016/j.jaci.2020.08.039DOI Listing
January 2021

Sensitivity and specificity of double-blinded penicillin skin testing in relation to oral provocation with amoxicillin in children.

Allergy Asthma Clin Immunol 2020 1;16:57. Epub 2020 Jul 1.

Pediatric Allergy and Clinical Immunology, CHU Sainte-Justine, Montreal, Canada.

Current recommendations for the management of penicillin allergy are to perform penicillin skin testing (PST) with penicilloyl-polylysine (PPL) and benzylpenicillin (BP) prior to drug challenge with amoxicillin. However, the role of PST is increasingly questioned in the pediatric setting. To resolve the question of PST's diagnostic accuracy, consecutive children with a history of non-life-threatening penicillin allergy referred to a tertiary-care allergy center were recruited to undergo double-blinded PST with PPL and BP prior to drug provocation to amoxicillin. Five of 158 participants (3.2%) presented with an immediate or accelerated reaction upon amoxicillin challenge, none of which were severe. Only one of these had positive PST (20%), compared to 15 of 153 amoxicillin tolerant participants (9.8%). The sensitivity and specificity of PST with PPL and BP for reacting upon amoxicillin challenge were 20% (95% CI: 0.5-71.6%) and 90% (95% CI: 84.4-94.4%), respectively. These results argue against the routine use of PST as a preliminary step to drug provocation with amoxicillin in this population, as it is unlikely to significantly alter pre-test probability of reacting to challenge.
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http://dx.doi.org/10.1186/s13223-020-00449-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371808PMC
July 2020

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

J Allergy Clin Immunol 2020 10 10;146(4):863-874. Epub 2020 Jul 10.

DBV Technologies, Montrouge, France; Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY.

Background: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg).

Objective: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study.

Methods: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment.

Results: Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%).

Conclusions: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.
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http://dx.doi.org/10.1016/j.jaci.2020.06.028DOI Listing
October 2020

Economic considerations on the usage of biologics in the allergy clinic.

Allergy 2021 01 6;76(1):191-209. Epub 2020 Sep 6.

Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.

The advent of biologic therapies has transformed care for severe atopic disorders but their high cost poses new challenges with regard to long-term sustainability and fair allocation of resources. This article covers the basic concepts of cost-utility analyses and reviews the available literature on cost utility of biologic drugs in atopic disorders. When used within their limits as part of a multi-dimensional assessment, economic analyses can be extremely useful to guide decision-making and prioritization of care. Despite the good quality of most cost-utility analyses conducted for the use of biologics in asthma and other atopic diseases, their conclusions regarding cost-effectiveness are extremely variable. This is mainly due to the use of inconsistent estimates of health utility benefit with therapy. Development of reliable and validated instruments to measure disutility in atopic disorders and measure of indirect costs in atopic disease are identified as a priority for future research.
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http://dx.doi.org/10.1111/all.14494DOI Listing
January 2021

SF-6Dv2 preference value set for health utility in food allergy.

Allergy 2021 01 6;76(1):326-338. Epub 2020 Jul 6.

Department of Medicine, Université de Montréal, Montreal, QC, Canada.

Background: The lack of a value set allowing the calculation of QALY is an important limitation when establishing the value of emerging therapies to treat food allergy. The aim of this study was to develop a Short-Form Six-Dimension version 2 (SF-6Dv2) preference value set for the calculation of health utility from the Canadian food-allergic population.

Methods: Two hundred ninety-five parents of patients aged 0-17 years old and 154 patients aged 12 years old and above with food allergy were recruited in clinic and online. Participants were asked to complete a self-administered online questionnaire including generic health-related quality of life questionnaires. Various health states described by the SF-6Dv2 were valued with time-trade-off and discrete choice experiments. Data from elicitation techniques were combined using the hybrid regression model.

Results: A total of 241 parents and 125 patients performed 3904 time-trade-off and 5112 discrete choice experiments. Utility decrements were estimated for each level of each SF-6Dv2 dimension. Utility values calculated based on the validated preference set were in average 0.15 lower (95%CI: 0.12-0.18) and were poorly correlated (R  = 0.46) with those derived from the EQ-5D-5L generic questionnaire in the same cohort.

Conclusion: A representative preference value set for patients with food allergy was determined using the SF-6Dv2 generic questionnaire. This adapted preference set will contribute to improve the validity of future utility estimates in this population for the appraisal of upcoming potentially impactful but sometimes costly therapies.
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http://dx.doi.org/10.1111/all.14444DOI Listing
January 2021

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis.

CMAJ 2020 07 22;192(27):E745-E755. Epub 2020 May 22.

Indian Institute of Public Health-Delhi (Devasenapathy), Public Health Foundation of India, Gurgaon, Haryana, India; Department of Health Research Methods, Evidence and Impact (Ye, Loeb, Fang, Tadayon Najafabadi, Xiao, Couban, Guyatt), McMaster University, Hamilton, Ont.; Guangzhou University of Chinese Medicine (Fang), Guangzhou, Guangdong, China; West China School of Nursing and West China Hospital (Xiao), Sichuan University, Chengdu, Sichuan, China; Department of Medicine (Bégin), Université de Montréal, Que.

Background: The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections.

Methods: In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results: Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study ( = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza ( = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference -1.62, 95% CI -3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence).

Interpretation: Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.
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http://dx.doi.org/10.1503/cmaj.200642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828893PMC
July 2020

Polygenic risk score for atopic dermatitis in the Canadian population.

J Allergy Clin Immunol 2021 Jan 19;147(1):406-409. Epub 2020 May 19.

Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada; Centre intersectoriel en santé durable, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada; Department of Pediatrics, Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, Quebec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.04.057DOI Listing
January 2021

Accuracy of rating scale interval values used in multiple mini-interviews: a mixed methods study.

Adv Health Sci Educ Theory Pract 2021 03 6;26(1):37-51. Epub 2020 May 6.

Faculty of Medicine, Université de Montréal, Montreal, Canada.

When determining the score given to candidates in multiple mini-interview (MMI) stations, raters have to translate a narrative judgment to an ordinal rating scale. When adding individual scores to calculate final ranking, it is generally presumed that the values of possible scores on the evaluation grid are separated by constant intervals, following a linear function, although this assumption is seldom validated with raters themselves. Inaccurate interval values could lead to systemic bias that could potentially distort candidates' final cumulative scores. The aim of this study was to establish rating scale values based on rater's intent, to validate these with an independent quantitative method, to explore their impact on final score, and to appraise their meaning according to experienced MMI interviewers. A 4-round consensus-group exercise was independently conducted with 42 MMI interviewers who were asked to determine relative values for the 6-point rating scale (from A to F) used in the Canadian integrated French MMI (IFMMI). In parallel, relative values were also calculated for each option of the scale by comparing the average scores concurrently given to the same individual in other stations every time that option was selected during three consecutive IFMMI years. Data from the same three cohorts was used to simulate the impact of using new score values on final rankings. Comments from the consensus group exercise were reviewed independently by two authors to explore raters' rationale for choosing specific values. Relative to the maximum (A = 100%) and minimum (F = 0%), experienced raters concluded to values of 86.7% (95% CI 86.3-87.1), 69.5% (68.9-70.1), 51.2% (50.6-51.8), and 29.3% (28.1-30.5), for scores of B, C, D and E respectively. The concurrent score approach was based on 43,412 IFMMI stations performed by 4345 medical school applicants. It provided quasi-identical values of 87.1% (82.4-91.5), 70.4% (66.1-74.7), 51.2% (47.1-55.3) and 31.8% (27.9-35.7), respectively. Qualitative analysis explained that while high scores are usually based on minor details of relatively low importance, low scores are usually attributed for more serious offenses and were assumed by the raters to carry more weight in the final score. Individual drop or increase in final MMI ranking with the use of new scale values ranged from - 21 to + 5 percentiles, with the average candidate changing by ± 1.4 percentiles. Consulting with experienced interviewers is a simple and effective approach to establish rating scale values that truly reflects raters' intent in MMI, thus improving the accuracy of the instrument and contributing to the general fairness of the process.
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http://dx.doi.org/10.1007/s10459-020-09970-1DOI Listing
March 2021

Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy.

Allergy Asthma Clin Immunol 2020 17;16:25. Epub 2020 Apr 17.

1Department of Allergy and Immunology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC Canada.

Background: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost-benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol.

Methods: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms.

Discussion: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication. ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301.
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http://dx.doi.org/10.1186/s13223-020-00419-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165401PMC
April 2020

Impact of a dietitian-led counseling program to support transition to whole foods during oral immunotherapy.

J Allergy Clin Immunol Pract 2020 06 26;8(6):2107-2109.e3. Epub 2020 Feb 26.

Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada; Allergy Section, Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, Quebec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.02.014DOI Listing
June 2020

The value of oral immunotherapy.

Allergy 2020 06;75(6):1291-1293

Departement of Medicine, Université de Montréal, Montreal, QC, Canada.

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http://dx.doi.org/10.1111/all.14072DOI Listing
June 2020

Visual assessment does not reliably predict peanut content in chocolate-covered peanut candies used for oral immunotherapy.

J Allergy Clin Immunol Pract 2020 01 11;8(1):368-370. Epub 2019 Sep 11.

Allergy Section, Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC, Canada; Allergy Section, Department of Medicine, Montreal University Hospital Center, Montreal, QC, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.08.046DOI Listing
January 2020

ICER report for peanut OIT comes up short.

Ann Allergy Asthma Immunol 2019 11 9;123(5):430-432. Epub 2019 Sep 9.

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, California. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2019.09.001DOI Listing
November 2019

Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses.

J Allergy Clin Immunol Pract 2019 Nov - Dec;7(8):2722-2738.e5. Epub 2019 Jun 4.

Centre Hospitalier Universitaire Sainte-Justine (CHU Sainte-Justine), Department of Pediatrics, Division of Clinical Immunology and Allergy, Université de Montréal, Montréal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Department of Medicine, Division of Clinical Immunology and Allergy, Montréal, QC, Canada.

Background: There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillin allergy.

Objectives: To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillin allergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity.

Methods: MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains.

Results: Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergic patients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillin allergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergic patients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32).

Conclusions: Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillin allergy.
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http://dx.doi.org/10.1016/j.jaip.2019.05.038DOI Listing
October 2020

Epicutaneous peanut patch device for the treatment of peanut allergy.

Expert Rev Clin Immunol 2019 05 27;15(5):449-460. Epub 2019 Mar 27.

a Department of Allergy and Immunology , Centre Hospitalier Universitaire Sainte-Justine , Montreal , QC , Canada.

Introduction: Food allergy prevalence has increased in recent decades, which has mobilized efforts to develop treatment alternatives. Epicutaneous immunotherapy (EPIT) is a novel method that involves transdermal administration of peanut allergen with the objective to induce tolerance. Recent clinical trials have shown its efficacy at increasing the eliciting dose in children with a favorable safety profile. Areas covered: This review covers the proposed mechanism of action of EPIT in murine models and humans, efficacy and safety data from clinical trials with peanut EPIT, and a discussion on its potential role in the future management of peanut allergy. Expert opinion: With the recent completion of pivotal trials for peanut EPIT and upcoming marketing, the main question for clinicians and food allergic patients is how to define its role in the management of peanut allergy and how it compares to oral immunotherapy (OIT). Like OIT, EPIT seems to promote immunological tolerance over time. However, EPIT could lack the rapid mast-cell desensitization induced by the progressive intake of food in OIT, which explains differences in short-term outcomes and safety profiles. Head-to-head and long-term comparison of real-life efficacy with regards to sustained unresponsiveness will help define its place in the food allergy arsenal.
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http://dx.doi.org/10.1080/1744666X.2019.1593138DOI Listing
May 2019

Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial.

JAMA 2019 03;321(10):946-955

Massachusetts General Hospital, Boston.

Importance: There are currently no approved treatments for peanut allergy.

Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children.

Design, Setting, And Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n = 356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein.

Interventions: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months.

Main Outcomes And Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs).

Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P < .001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group.

Conclusions And Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.

Trial Registration: ClinicalTrials.gov Identifier: NCT02636699.
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http://dx.doi.org/10.1001/jama.2019.1113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439674PMC
March 2019