01 Investigating the prevalence, accuracy of self-reporting, and mental health impacts of allergic disease in health care professional students during the COVID-19 pandemic
Alyssa G. Burrows1,2, Sydney Joy1,2,3, Sarah Garvey1, Sophia Linton1,2, Jenny Thiele1,2, Lisa M. Steacy2, Dean A. Tripp4, Anne K. Ellis1,2,3
1Department of Medicine, Queen’s University, Kingston, ON, Canada, 2Allergy Research Unit, Kingston, ON, Canada, 3Department of Biomedical Medical Sciences, Queen’s University,, Kingston, ON, Canada, 4Department of Psychology, Anesthesia, Urology, Queen’s University,, Kingston, ON, Canada
Correspondance: Alyssa G. Burrows
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 01
Background: COVID-19 symptoms overlap with allergic rhinitis (AR) and asthma, potentially impacting mental well-being . Research regarding the effects of anxiety and stress on Health Care Professional (HCP) students throughout the COVID-19 pandemic is beginning to emerge. It is currently unknown if trainees with atopic conditions experience different stress levels than their non-atopic peers. In Canadian adults, the estimated prevalence for AR and food allergy(FA) is 44% and 6.1%, respectively [2,3].
Methods: Between August 2020 to June 2021, Faculty of Health Sciences students (n = 266) completed a one-time questionnaire using the QualtricsXMTMsurvey platform of which 114 respondents disclosed their atopic status. The following data was collected: Self-reported atopy status, Generalized Anxiety Disorder-7(GAD-7), Patient Health Questionaire-9(PHQ-9), and Perceived Stress Score-10(PSS-10). Participants were then classified based on the type and number of atopic conditions they reported. A follow-up visit involving skin prick testing (SPT) to a standard panel of 9 aeroallergen and food extracts, and/or fresh fruits, where applicable, was completed (n = 34) to determine how accurately allergies were self-reported. Statistical analyses were performed using SPSS 27.
Results: Having a self-reported allergic condition or asthma did not impact GAD-7, PSS, and PHQ-9 scores, in HCP students. Further stratifying the dataset by the type and number of allergic conditions also did not impact GAD-7, PSS, and PHQ-9 scores or severity. The self-reported prevalence of asthma, AR and FA was 5.71%, 64.71%, and 29.41%, respectively. SPT confirmed 64.71% and 8.82% of participants were sensitized to AR and food allergens, respectively. Generally, seasonal AR allergies were underreported whereas, perennial AR and FA were overreported.
Conclusions: Atopic conditions did not impact mental health scores in HCP student’s which suggests that they are generally aware of their atopic conditions and able to differentiate allergy and COVID-19 symptoms. Self-reported accuracy varied and may be impacted by the specific allergic condition.
Shaker MS, Oppenheimer J, Grayson M, Stukus D, Hartog N, Hsieh EW, Rider N, Dutmer CM, Vander Leek TK, Kim H, Chan ES. COVID-19: pandemic contingency planning for the allergy and immunology clinic. The Journal of Allergy and Clinical Immunology: In Practice. 2020 May 1;8(5):1477–88.
Keith PK, Desrosiers M, Laister T, Schellenberg RR, Waserman S. The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients. Allergy, Asthma & Clinical Immunology. 2012 Dec;8(1):1–1.
Clarke AE, Elliott SJ, Pierre YS, Soller L, La Vieille S, Ben-Shoshan M. Temporal trends in prevalence of food allergy in Canada. The Journal of Allergy and Clinical Immunology: In Practice. 2020 Apr 1;8(4):1428–30.
02 Triple therapy (LAMA, ICS and LABA) in asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis
Anna Whalen-Browne, Lisa Kim, Carol Saleh, Paul O’Byrne, Derek Chu
McMaster University, Hamilton, ON, Canada
Correpondance: Anna Whalen-Browne
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 02
Background: Among patients with moderate-severe asthma, benefits and harms of adding long-acting muscarinic antagonists (LAMA) to inhaled corticosteroids (ICS) and long-acting bronchodilators (LABA) remains unclear due to lack of systematic reviews and meta-analyses. The latest asthma recommendations comment on only one LAMA and include fewer than five studies from before 2017. The objective of this study was to systematically synthesize the efficacy and safety of triple (ICS-LABA-LAMA) vs. dual therapy (ICS-LABA) in persistent, uncontrolled asthma.
Methods: MEDLINE, EMBASE, CENTRAL, ICTRP, FDA and EMA databases from November 2017 to December 8, 2020 were searched. Two investigators independently selected randomized controlled trials (RCTs) comparing triple and dual therapy in moderate-severe asthma. Two reviewers independently extracted data and assessed risk of bias. Data was analysed using random-effects meta-analyses, including individual patient-level exacerbation data. GRADE approach was used to assess certainty. The primary outcome was severe exacerbations (risk ratio [RR], incidence rate ratio [IRR], hazard ratio [HR]). Secondary outcomes included asthma control, quality of life, FEV1, and adverse events. PROSPERO number CRD42020172608.
Results: Twenty RCTs that enrolled 11,894 patients and used three LAMA types were included. High certainty evidence revealed that compared with dual therapy, triple therapy decreased the number of severe asthma exacerbations (RR 0.83, 95% CI 0.77 to 0.90), and improved asthma control (SMD -0.06, 95% CI − 0.10 to − 0.02; MD in ACQ-7 scale − 0.04, 95% CI − 0.07 to − 0.01). There were no significant differences in asthma-related quality of life (SMD 0.05, 95% CI − 0.03 to 0.13; MD in AQLQ scale 0.05, 95% CI − 0.03 to 0.13) or mortality (RR 0.96, 95% CI 0.33 to 2.75). Adverse events were similar between groups.
Conclusions: In moderate-severe asthma, triple therapy safely reduces severe exacerbations with modest improvements in other patient-important outcomes. This supports add-on LAMA in patients at high risk for future exacerbation.
03 Serum biomarkers and Staphylococcus aureus carriage in ragweed-induced allergic rhinitis using the nasal allergen challenge model
Sophia Linton1,2, Jenny Thiele1,2, Lisa M. Steacy2, Lubnaa Hossenbaccus1,2, Anne K. Ellis1,2
1Department of Medicine, Queen’s University, Kingston, ON, Canada, 2Kingston Allergy Research, Kingston Health Sciences Center - KGH Site, Kingston, ON, Canada
Correspondance: Sophia Linton
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 03
Background: The relationship between Staphylococcus aureus(SA) nasal carriage and allergic rhinitis blood biomarkers is not known. The current study compares ragweed(RW) specific(s) immunoglobulin-E(IgE) levels and serum cytokine levels and in RW-allergic participants colonized with and without SA. The allergen exposure was modeled using the nasal allergen challenge model(NAC), which consists of a screening and challenge visit.
Methods: Nasal SA carriage was assessed using culture-based screening methods in 15 RW-allergic participants before their NAC with individualized RW-extract doses determined using a titration challenge. Peripheral blood samples collected at the screening visit were used to evaluate sIgE levels, while those collected at the challenge visit were used to evaluate serum cytokine(baseline, 6- and 24-hour post-NAC). The cytokines IL-1b, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-a, IFN-g, MCP-1, MIP-1b, and RANTES were measured using Luminex xMAPTM technology, and sIgE concentrations were measured using an ImmunoCAP assay on the Phadia® 100 machine. All statistical analyses were performed on GraphPad Prism 9.0.
Results: Four RW-allergic participants were colonized with antibiotic-sensitive SA (SA+), and 11 were not(SA-). The sIgE (p = 0.3429) levels were not significantly different between the two populations. The concentration of MCP-1 at 24-hours was significantly higher in SA+ than SA- (p = 0.0399). MIP1-b (p = 0.0170) and IFN-g (p = 0.0214) concentrations were significantly elevated in SA- at 24-hours compared to baseline. Individual cytokine levels were widely distributed, and therefore the change in cytokine levels from baseline was calculated. The change in IL-5 concentration at 6-hours compared to baseline was significantly greater in SA+ than SA-(p = 0.0148).
Conclusions: There is differential cytokine expression in the blood of SA+ and SA- populations post-NAC while sIgE levels were not significantly different. These results suggest that SA carriage may impact the allergic response to RW exposure in the peripheral blood, however more investigations are needed to support these findings and identify potential mechanistic pathways.
04 The role of gut microbiota in mediating allergic asthma in infants
John Christy Johnson, Peter Anto Johnson, Austin Mardon
University of Alberta, Edmonton, AB, Canada
Correspondance: John Christy Johnson
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 04
Background: Allergic asthma in infants represents an increasingly common chronic disease, classically associated with hyperactivation of the T helper 2 (Th2) arm of adaptive immunity . Recent culture-independent molecular detection technology presents growing evidence in rodent models that reveal correlations between allergic asthma with gut microbiota [1,2]. However, the mechanism of gut microbial strains in inducing chronic inflammation-related changes in infants with allergic asthma are still poorly understood . Here, we conducted a narrative review to synthesize current evidence in the literature.
Methods: We conducted a review of the literature followed by a qualitative narrative synthesis following ENTREQ guidelines. Databases including PubMed/MEDLINE, EMBASE and Google Scholar were screened, and no time, setting, or language restrictions were imposed on the search strategy. Keywords in our search included: “allergic asthma”, “dysbiosis”, “gut microbiota”, “prebiotic” or “probiotic,” “Th2”, “adaptive immunity” and “IgE”. Primary research articles such as case studies, systematic reviews and meta-analyses, were included. Technology-based, animal, and non-infant studies were excluded.
Results: We identified 25 articles that met our inclusion criteria. Of the 25, fourteen discussed the role of specific microbial species that were associated with either pathogenic or protective roles in allergic asthma in infants. Four were systematic reviews identifying 346 cases cumulatively and evaluating outcomes and discussing risk factors. Three major mechanisms, including cesarean birth, formula feeding, and early-life exposure to antimicrobials accumulated the greatest mentions in literature. Maternal factors such as exposure to livestock/pets and antimicrobial use during pregnancy were further characterized or mentioned by 8 studies.
Conclusions: Evidence appears to suggest gut microbial flora is likely influenced by nutrition, medications, birth conditions, maternal factors, and environmental exposures. Numerous retrospective studies, case studies, and reviews and therapeutic applications of early prebiotic/probiotic therapy corroborate these mechanisms , but do not exclude other plausible manners in which gut dysbiosis induces and/or exacerbates allergic asthma.
Di Gangi A, Di Cicco ME, Comberiati P, Peroni DG. Go With Your Gut: The Shaping of T-Cell Response by Gut Microbiota in Allergic Asthma. Front Immunol. 2020 Jul 14;11:1485. doi: 10.3389/fimmu.2020.01485. PMID: 32760404; PMCID: PMC7372123.
Fujimura KE, Lynch SV. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe. 2015 May 13;17(5):592–602. doi: 10.1016/j.chom.2015.04.007. PMID: 25974301; PMCID: PMC4443817.
Kang YB, Cai Y, Zhang H. Gut microbiota and allergy/asthma: From pathogenesis to new therapeutic strategies. Allergol Immunopathol (Madr). 2017 May-Jun;45(3):305–309. doi: 10.1016/j.aller.2016.08.004. Epub 2016 Oct 28. PMID: 28029408.
05 The 12-SQ HDM SLIT-tablet shows similar safety and efficacy across geographies, ethnic and age groups
Hendrik Nolte1, Tomokazu Matsuoka2, David I. Bernstein3, Yuriko Maekawa4, Veronica Hulstrøm5
1ALK, Bedminster, NJ, USA, 2Department of Otorhinolaryngology, Head & Neck Surgery, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan, 3Bernstein Clinical Research Center and Division of Immunology, Allergy and Rheumatology, University of Cincinnati, Cincinnati, OH, USA, 4Torii Pharmaceuticals Co., Ltd., Tokyo, Japan, 5ALK, Hørsholm, Denmark
Correspondance: Hendrik Nolte
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 05
Background: House dust mite (HDM) sublingual immunotherapy (SLIT)-tablets have been evaluated in large clinical trials of adolescents and adults with allergic rhinoconjunctivitis in North America and Japan. Because of the diversity of participants in the trials and the large sample sizes, it is possible to assess safety and efficacy across age groups and world regions.
Methods: Efficacy and safety data from 2 randomized, double-blind, placebo-controlled phase III clinical trials (NCT01700192 and JapicCTI-121848) with 12-SQ HDM were analysed by age (12–17 years/18–64 years) and ethnicity/region (Japan/North America [NA]). Trials were designed similarly with respect to medical practice, target population, eligibility criteria, efficacy and safety monitoring.
Results: The treatment effect on the primary endpoint of total combined rhinitis score (TCRS) in Japanese (N = 633) and NA (N = 1482) subjects were comparable both for the overall trial populations and the adolescent and adult subgroups, ranging between 16–22% relative to placebo. HDM SLIT-tablet was well tolerated, and in general, the safety profile was similar in Japanese and NA populations. The placebo-subtracted treatment-related adverse event (AE) rate in NA adolescents/adults was 45%/41% and in Japanese adolescents/adults was 47%/46%. There was no epinephrine use due to treatment-related events in adolescent subjects in either trial. Only 4 events of epinephrine use due to treatment-related events were reported among NA adult subjects. The HDM IgE and IgG4 responses were comparable between Japanese and NA subjects and between age groups.
Conclusions: In conclusion, the results show that SQ HDM SLIT-tablet is insensitive to ethnic, age or regional differences with a similar safety, efficacy, and immunologic profile.
06 Dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps: Results from the SINUS trials
Philippe Gevaert1, Stella E. Lee2, Russell Settipane3, Martin Wagenmann4, Jérôme Msihid5, Shahid Siddiqui6, Scott Nash6, Juby A. Jacob-Nara7, Asif H. Khan8, Siddhesh Kamat6, Chien-Chia Chuang9
1Department of Otorhinolaryngology, Ghent University, Ghent, Belgium, 2Department of Otolaryngology—Head & Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA, 3Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA, 4Department of Otorhinolaryngology, Düsseldorf University Hospital (UKD), Düsseldorf, Germany, 5Health Economics and Value Assessment, Sanofi, Chilly-Mazarin, France, 6Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 7Global Medical Affairs, Sanofi, Bridgewater, NJ, USA, 8Global Medical Affairs, Sanofi, Chilly-Mazarin, France, 9Health Economics and Value Assessment, Sanofi, Cambridge, MA, USA
Correspondance: Philippe Gevaert
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 06
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease, with cardinal symptoms of nasal congestion (NC), loss of smell (LoS), and rhinorrhea significantly impacting patients’ daily lives. We report dupilumab’s effect on patient-reported CRSwNP symptoms from the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies.
Methods: Post hoc analysis in CRSwNP patients receiving dupilumab 300 mg or placebo q2w. Pooled SINUS-24/-52 intent-to-treat (ITT) population (N = 724) was used for assessment to Week 24 and SINUS-52 population (N = 303) for Week 52 assessment. Patients reported symptom scores (0 = none; 1 = mild; 2 = moderate; 3 = severe) daily for NC, LoS, and rhinorrhea. Proportions of patients with baseline scores ≥2 (moderate/severe) achieving improvement (score ≤1; none/mild) at Weeks 2, 24, and 52 were reported for the ITT population and subgroups with asthma/prior sinonasal surgery.
Results: At baseline, 86.7%, 94.1%, and 64.1% of patients had scores ≥2 for NC, LoS, and rhinorrhea, respectively. Significantly more patients achieved improvement (score ≤1; none/mild symptoms) with dupilumab vs placebo at Weeks 2/24/52 (dupilumab vs placebo, NC: 11.5%/54.2%/54.6% vs 1.6%/13.7%/15.9%; LoS, 5.1%/43.4%/43.8% vs 1.1%/5.5%/4.2%; rhinorrhea, 9.4%/53.2%/58.3% vs 2.2%/15.6%/20.4%). Results were consistent across subgroups at Weeks 24 and 52. Among patients not achieving scores ≤1 at Week 24, more dupilumab- vs placebo-treated patients experienced symptom improvement (scores of > 1–≤ 2).
Conclusions: In CRSwNP patients with moderate-to-severe symptom burden at baseline, dupilumab significantly improved patient-reported symptoms vs placebo. Symptom improvement was observed as early as Week 2, and continued to Week 52, suggesting early onset, durable treatment effect of dupilumab.
07 Time-varying effects of allergy on the childhood asthma risk: a retrospective cohort study
Rui Li1, Arthur H. Owora1,3, Robert S. Tepper2, Clare D. Ramsey4, Moira Chan-Yeung5, Wade T. Watson6, Allan B. Becker3
1Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN, USA, 2Indiana University School of Medicine, Indianapolis, IN, USA, 3Children’s Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada, 4Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada, 5Department of Medicine, University of British Columbia, Vancouver, BC, Canada, 6Department of Pediatrics, Dalhousie University, Halifax, NS, Canada
Correspondance: Rui Li
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 07
Background: The relationship between childhood allergies and asthma is heterogeneous and time-dependent; however, there is a paucity of research on how different allergy patterns impact asthma risk over time. Our study objective was to examine the effect of different allergy patterns on asthma risk from birth to adolescence.
Methods: Secondary analysis of the Canadian Asthma Primary Prevention Study (CAPPS), a multifaceted prenatal intervention among children at high risk of asthma, followed from birth to 15 years was performed. Asthma and allergy diagnoses were based on a pediatric allergist’s clinical decision and skin prick test results, respectively. Marginal Structural Modeling (MSM) was used to examine whether asthma risk differs among children with different allergy histories at ages 1, 2, 7 and 15 years. Transition models were used to quantify the lagged effect of prior allergies at 7 and 15 years.
Results: On average, the odds of asthma were higher among children who had at least one positive allergy skin test result in the 1st year (adjusted odds ratio [aOR]: 1.47; 95% CI: 1.15, 1.86); this association persisted for different skin test reactivity patterns over time. Irrespective of a child’s allergy history, the odds of asthma were lower among children randomized to the CAPPS intervention (aOR: 0.56; 95% CI: 0.42, 0.75). The effect of prior allergies on future diagnoses decreased over time (at age 7 years OR: 2.39; 95% CI: 2.00, 2.86 and at 15 years OR:1.46; 95% CI: 1.18, 1.81).
Conclusions: The magnitude and persistence of allergy effects on asthma risk during childhood into adolescence suggests greater efforts should be devoted to early allergy screening and preventive intervention.
Dick, S., et al., A systematic review of associations between environmental exposures and development of asthma in children aged up to 9 years. BMJ Open, 2014. 4(11): p. e006554.
08 Modeling multi-state childhood allergy-asthma transitions: a retrospective cohort study
Arthur H. Owora1, Robert H. Tepper2, Clare H. Ramsey3, Moira H. Chan-Yeung4, Wade H. Watson5, Allan H. Becker6
1Indiana University School of Public Health, Bloomington, IN, USA, 2Indiana University School of Medicine, Indianapolis, IN, USA, 3Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada, 4Department of Medicine, University of British Columbia, Vancouver, BC, Canada, 5Department of Pediatrics, Dalhousie University, Halifax, NS, Canada, 6Children’s Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
Correspondance: Arthur H. Owora
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 08
Background: Two-thirds of childhood asthma diagnoses especially severe cases have allergic origins[1, 2]. Prior to an asthma diagnosis, children may experience a time-varying burden of allergies as they grow older. Modeling these transitions can provide insights regarding disease pathogenesis and prognostic factors that influence disease progression. Our study objective was to characterize the natural course of allergy-mediated childhood asthma.
Methods: We carried out a secondary analysis of the Canadian Asthma Primary Prevention Study (CAPPS), a multifaceted prenatal intervention among children at high risk of asthma, followed from birth to 15 years. Asthma and allergy diagnoses were based on a pediatric allergist’s clinical decision and positive skin test results to food or non-food allergens, respectively. A staged Markov model was used to estimate the distribution, mean time to asthma diagnosis, and transition ratios between allergy-asthma states for 493 children.
Results: Our transition model had four bi-directional stages: I) no allergies/asthma, II) one allergy/no asthma, III) ≥ 2 allergies/no asthma, and IV) current asthma diagnosis; the average (standard error) duration in each stage was 15(2.9), 3(0.4), 11(2.4) and 8(2.3) years, respectively. The mean time to an asthma diagnosis was 10.2 years (95%CI: 1.7, 11.0). Adjusted for CAPPS intervention, transition to an asthma diagnosis was more likely from stage II (Transition Ratio [TR]: 3.4; 95%CI: 1.4, 8.0) and III (TR: 2.8; 95%CI: 1.5, 5.4) than Stage I. Recovery (i.e., reverse association) was more likely than disease progression from Stage II (TR 3.6; 95%CI: 1.92, 11.04) but less likely from Stage III (TR: 0.16; 95%CI: 0.1, 0.5) or IV (TR: 0.33; 95%CI: 0.1, 0.8).
Conclusions: Among children at high-genetic risk, allergy-mediated asthma risk appears to be reversible before but not after multiple sensitizations to aeroallergens. Our findings support prioritization of prevention efforts that mitigate early sensitization.
Holt, P.G., et al., The role of allergy in the development of asthma. Nature, 1999. 402(6760 Suppl): p. B12–7.
GINA Report 2020; Global Strategy of Asthma Management and Prevention.
09 Long-term impact of dupilumab on the reduction of oral corticosteroid (OCS) use in patients with OCS-dependent asthma
Lawrence D. Sher1, Michael E. Wechsler2, Klaus F. Rabe3,4, Jorge F. Maspero5, Nadia Daizadeh6, Xuezhou Mao7, Benjamin Ortiz8, Leda P. Mannent9, Elizabeth Laws7, Nami Pandit-Abid7, David J. Lederer8, Megan Hardin6
1Peninsula Research Associates, Rolling Hills Estates, CA, USA, 2National Jewish Health, Denver, CO, USA, 3LungenClinic Grosshansdorf (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Grosshansdorf, Germany, 4Christian-Albrechts University (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Kiel, Germany, 5Fundación CIDEA, Buenos Aires, Argentina, 6Sanofi, Cambridge, MA, USA, 7Sanofi, Bridgewater, NJ, USA, 8Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 9Sanofi, Chilly-Mazarin, France
Correspondance: Lawrence D. Sher
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 09
Background: Patients with severe asthma may require long-term oral corticosteroids (OCS) treatment to control disease. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/interleukin-13, key/central drivers of type 2 inflammation in multiple diseases. In VENTURE (NCT02528214), dupilumab 300mg vs placebo reduced OCS dose and exacerbations and improved lung function in patients with OCS-dependent severe asthma. TRAVERSE, a single-arm, open-label extension study (NCT02134028), evaluated long-term safety, tolerability, and efficacy of dupilumab. We evaluated long-term maintenance of OCS reduction and clinical efficacy in VENTURE patients enrolled in TRAVERSE.
Methods: LS mean percentage change from parent study baseline (PSBL) in OCS use and percentage of patients with OCS reduction ≥50%, annualized exacerbation rate, LS mean change from PSBL in lung function (FEV1), and mean change from PSBL in asthma control (ACQ-5) at TRAVERSE Week48 were evaluated in VENTURE patients receiving dupilumab (dupilumab/dupilumab) or placebo (placebo/dupilumab) enrolled in TRAVERSE.
Results: VENTURE patients treated with dupilumab enrolled in TRAVERSE reduced LS mean OCS dose by 68.8% from PSBL to end of VENTURE. LS mean OCS dose was reduced by 78.3% (dupilumab/dupilumab) and 53.4% (placebo/dupilumab) from PSBL to TRAVERSE Week48. 74/90 dupilumab and 52/97 placebo patients achieved ≥50% reduction in OCS dose by end of VENTURE. Of evaluable patients, 47/49 (dupilumab/dupilumab) and 37/39 (placebo/dupilumab) sustained OCS reduction at TRAVERSE Week48. Unadjusted annualized exacerbation rates over TRAVERSE Weeks 0–48 were 0.442 (dupilumab/dupilumab) and 0.321 (placebo/dupilumab). FEV1 (L) increased (LS mean change [SE]: 0.25 [0.06] and 0.25 [0.05]) and ACQ-5 improved (mean change [SD]: – 1.06 [1.25] and – 1.21 [1.00]) from PSBL to TRAVERSE Week48 in dupilumab/dupilumab and placebo/dupilumab, respectively.
Conclusions: Patients with severe OCS-dependent asthma demonstrated sustained OCS dose reduction and clinical outcomes improvement during TRAVERSE. The OCS-sparing effect, exacerbation reduction, and lung function and asthma control improvements of dupilumab observed in VENTURE were maintained in TRAVERSE.
10 Impact of severe exacerbations on lung function in patients with uncontrolled, moderate-to-severe asthma treated with dupilumab: LIBERTY ASTHMA QUEST
Kenneth R. Chapman1, Alberto Papi2, Mario Castro3, Daniel J. Jackson4, Nadia Daizadeh5, Nami Pandit-Abid6, Yamo Deniz7, Paul J. Rowe6, Benjamin Ortiz7
1University of Toronto, Toronto, ON, Canada, 2Respiratory Medicine Unit, University of Ferrara, S. Anna University Hospital, Ferrara, Italy, 3University of Kansas School of Medicine, Kansas City, KS, USA, 4University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, 5Sanofi, Cambridge, MA, USA, 6Sanofi, Bridgewater, NJ, USA, 7Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA
Correspondance: Kenneth R. Chapman
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 10
Background: Severe asthma exacerbations are associated with lung function impairment. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/interleukin-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200/300mg every 2 weeks vs placebo reduced severe exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated T2 biomarkers. This post hoc analysis assessed the impact of severe exacerbations on post-bronchodilator FEV1 in QUEST patients with T2 inflammatory asthma.
Methods: Change from baseline in post-bronchodilator FEV1 was assessed in QUEST patients with T2 phenotypes (≥150 eosinophils/µL and/or FeNO ≥ 25ppb or ≥ 300 eosinophils/µL and/or FeNO ≥ 25ppb) who did/did not experience asthma exacerbations during QUEST, and in patients after experiencing a first severe exacerbation.
Results: Post-bronchodilator FEV1 recovered faster after exacerbation in dupilumab patients. Greater benefits were observed within 6 weeks of exacerbation and were sustained over time. Patients with ≥ 300 eosinophils/µL and/or FeNO ≥ 25ppb at baseline benefited most from dupilumab after first severe exacerbation event (LS mean difference vs placebo [95% CI], ≥ 150 eos/≥ 300 eos: Week3: 0.13L [0.06–0.20]/0.14L [0.06–0.22], Week12: 0.06L [– 0.01 to 0.12]/0.08L [– 0.002 to 0.16], Week24: 0.07L [– 0.02–0.15]/0.09L [– 0.01 to 0.18]). Exacerbator and non-exacerbator post-bronchodilator FEV1 was comparable between dupilumab and placebo groups at study baseline. At Week12, improvements in post-bronchodilator FEV1 were greater in dupilumab groups, irrespective of exacerbations or baseline eosinophil levels (LS mean difference vs placebo [95% CI]; exacerbators: ≥150 eos/≥300 eos: 0.14L [0.08–0.20], P < 0.0001/0.17L [0.10–0.24], P < 0.0001; non-exacerbators: ≥ 150 eos/≥300 eos: 0.14L [0.09–0.19], P < 0.0001/0.18L [0.13–0.24], P < 0.0001). Improvements were sustained over time.
Conclusions: Dupilumab reduced the impact of exacerbations and improved post-bronchodilator FEV1 in T2 inflammatory asthma patients, regardless of exacerbation status. Lung function improvements after exacerbation were rapid and sustained in dupilumab patients.
11 Randomized controlled trial of ragweed sublingual immunotherapy tablet in subpopulation of Canadian children with allergic rhinoconjunctivitis
Rémi Gagnon1, Anne K. Ellis2, David I. Bernstein3, Hendrik Nolte4
1Clinique Spécialisée en Allergie de la Capitale, Québec, QC, Canada, 2Department of Medicine, Queen’s University, Kingston, ON, Canada, 3Department of Internal Medicine, University of Cincinnati College of Medicine and Bernstein Clinical Research Center, Cincinnati, OH, USA, 4ALK, Bedminster, NJ, USA
Correspondance: Rémi Gagnon
Allergy, Asthma & Clinical Immunology 2022, 17(Suppl 1): 11
Background: Post hoc analyses of randomized placebo-controlled trials have demonstrated efficacy and tolerability of the ragweed sublingual immunotherapy (SLIT)-tablet in Canadian adults with ragweed pollen-induced allergic rhinitis/conjunctivitis (AR/C). This analysis evaluated the efficacy and tolerability of the ragweed SLIT-tablet in the subpopulation of Canadian children with AR/C in a previously described randomized, double-blind, placebo-controlled trial.
Methods: The trial (NCT02478398) was conducted in North American and European children ages 5–17 years with ragweed pollen-induced AR/C with or without asthma. Participants were randomized to daily ragweed SLIT-tablet (12 Amb a 1-U) or placebo for up to 28 weeks. The primary endpoint was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Post hoc analyses were conducted in the Canadian participants. All statistical analyses were per protocol.
Results: Of the 1025 randomized participants, 246 (SLIT-tablet, n = 116; placebo, n = 130) were in the Canadian subpopulation. In the total study population, relative TCS (95% CI) improvement with ragweed SLIT-tablet versus placebo was − 38.3% (− 46.0%, − 29.7%; least square [LS] mean difference, − 2.73; P<0.001) during peak RPS. In the Canadian subpopulation, relative TCS improvements with ragweed SLIT-tablet versus placebo were − 40.8% (− 54.5%, − 20.2%; LS mean difference, − 1.59; P = 0.001) during peak RPS and − 36.6% (− 50.2%, − 16.5%; LS mean difference, − 1.36; P = 0.002) during the entire RPS. DSS and DMS during peak RPS in the Canadian subpopulation improved with SLIT-tablet versus placebo by − 30.6% (− 45.2%, − 7.7%; LS mean difference, − 0.94; P = 0.01) and − 77.2% (− 97.5%, − 44.2%; LS mean difference, − 0.66; P = 0.003), respectively. No events of anaphylaxis, airway compromise, eosinophilic esophagitis, or severe treatment-related systemic allergic reactions were reported in the overall population or Canadian subpopulation.
Conclusions: The ragweed SLIT-tablet resulted in clinically meaningful improvement in symptoms, decreased symptom-relieving medication use, and was well tolerated in Canadian children.