273 research outputs found

    Efficacy of Dupilumab in Patients with Moderate-to-Severe Asthma and Persistent Airflow Obstruction

    No full text
    Background: The 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged ≄12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo. Objective: To assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio <0.7 at baseline. Methods: Endpoints were annualized rate of severe exacerbations, pre-/post-bronchodilator FEV 1 over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with/without PAO at baseline in subpopulations with eosinophils ≄ 150 cells/”L or fractional exhaled nitric oxide (FeNO) ≄ 25 ppb, or eosinophils ≄ 300 cells/”L and FeNO ≄ 25 ppb. Results: Of 1,902 patients enrolled in QUEST, 1,039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% CI 1.272-2.052], and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk [RR], 95% CI 0.411 [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils ≄150 cells/”L or FeNO ≄25 ppb, and eosinophils ≄300 cells/”L and FeNO ≄25 ppb, respectively. Similar results were observed in patient subgroups without PAO. Conclusion: In patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes

    Updated guidance regarding the risk ofAllergic reactions to COVID-19 vaccines and recommended evaluation and management: a GRADE assessment, and international consensus approach.

    No full text
    This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommenations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise, in a properly equipped setting. We suggest against pre-medication, split-dosing, or special precautions because of a comorbid allergic history

    Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

    Get PDF
    Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.The authors thank Tania Bray, Jan Hempstead, Heather Mayne, Joanne Mulder-Brambleby, and Irene Wilson for their supporting contributions, and all patients and families affected by MCDs, who shared their needs and concerns for development of this project. Authors involved in study conception and design were P. Valent, S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, and C. Zubrinich. Authors involved in acquisition and review of data were S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, C. Zubrinich, and P. Valent. The Core Group (analysis and interpretation of data and drafting of the manuscript) include S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, and V.M. Slee. Critical revision was performed by S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F Wimazal, T. Yigit, C. Zubrinich, and P. Valent

    Autoantibodies against type I IFNs in humans with alternative NF-ÎșB pathway deficiency

    Get PDF

    [In Press] Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients

    No full text
    Background: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. Methods: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≀1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≄80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. Results: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. Conclusion: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure

    Dupilumab reduced severe exacerbation rates and improved pre-bronchodilator Fev 1 in patients with moderate-to-severe asthma regardless of exacerbation history of 蠅1, 蠅2, or 蠅3 prior exacerbations: Liberty Asthma Traverse

    No full text
    This is the author accepted manuscript. The final version is available from the American Thoracic Society via the DOI in this record Sanofi and Regeneron Pharmaceuticals, Inc

    Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach

    Get PDF
    This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against \u3e 15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history

    Evaluation of the performance of short-term curated daily airborne grass pollen forecasts in diverse biogeographical regions during the AusPollen Partnership project 2016–2020

    Full text link
    When providing pollen forecasts to the community, there is a need to verify the accuracy of curated forecasts, but evaluation is not routinely reported. This study of the AusPollen Partnership compared multi-category grass pollen forecasts for up to six days ahead with daily airborne grass pollen concentrations measured in Brisbane, Canberra, Melbourne, and Sydney, Australia during four pollen seasons from 2016 to 2020. The accuracy of categorical grass pollen forecasts predicting grass pollen concentrations in the high and greater, or moderate and greater categories, were assessed as often applied in meteorology using Gerrity scores, equitable threat scores, false alarm ratios, success ratios, and probability of detection of correct category. The skill of grass pollen forecasts curated by aerobiologists were compared with two retrospectively calculated naĂŻve reference forecast methods; climatology and persistence. For Brisbane and Melbourne, high or greater grass pollen levels occurred on average 32% and 22% of days, whereas for Canberra and Sydney, there were few high days, but moderate or greater pollen levels occurred on average 26% and 19% of days, respectively. Average annual Gerrity scores for curated forecasts of high or greater improved with experience from 0.20 to 0.66 in Brisbane, and from 0.39 to 0.55 in Melbourne between 2016 and 2019. Average Gerrity Scores for moderate or greater categories in Sydney were 0.45 and 0.43 in 2016 and 2018 respectively, and in Canberra were 0.34 and 0.41, in the same years. The skill of curated forecasts was usually better than persistence forecasts, but the accuracy of the curated forecasts decreased with longer lead times. Although persistence grass pollen forecasts consistently performed better than climatologies, persistence depends on previous day pollen concentrations being available. Short-term curated daily grass pollen forecasts of the AusPollen Partnership offer useful information for people with allergic rhinitis and asthma, to help facilitate behavioural change and reduce the health burden. There is a need in Australia to extend local pollen records through sustained pollen monitoring to track climate-related changes as well as improve reliability of daily pollen forecasts. Globally, continued evaluation will enable reporting of accurate pollen forecasts to community, clinicians and government stakeholders

    Use of adrenaline to manage suspected anaphylaxis following COVID-19 vaccination : an Australian retrospective cohort study

    No full text
    Background: The rate of anaphylaxis following COVID-19 vaccinations is estimated to be 2–11 cases per million doses administered. However, adrenaline is occasionally used in individuals who are later diagnosed with immunisation stress-related responses, as their initial presenting signs and symptoms can appear similar to that of anaphylaxis. This study aims to describe the clinical profile of individuals who had received adrenaline following a COVID-19 vaccine and their subsequent revaccination outcomes. Methods: We examined notifications of cases who had received adrenaline following a COVID-19 vaccine in New South Wales, Australia. The cases were classified into Brighton Collaboration Case Definition (BCCD) for anaphylaxis, their clinical presentation, management and subsequent revaccination outcomes were compared. Results: From 22 February 2021 to 30 September 2021, there were 222 cases where adrenaline was administered. Of these, 32 (14 %) fulfilled Level 1 BCCD, 59 (27%) Level 2, 2 (1%) Level 3, 97 (44%) Level 4 and 32 (14 %) Level 5. The most commonly reported symptoms were sensation of throat closure (n = 116, 52%), difficulty breathing (n = 82, 37%) and nausea (n = 55, 25 %). Of the 176 (79%) individuals who proceeded to further vaccination, 89 (51%) received the same vaccine formulation and only 14 (8%) experienced another allergic adverse event with 9 (5%) receiving adrenaline. Conclusion: Less than one in five individuals who received adrenaline met Level 1 BCCD criteria for anaphylaxis. Many reactions that were treated with adrenaline had little to no diagnostic certainty of anaphylaxis and in such cases repeat vaccination had a high likelihood of being tolerated. Increased awareness and education on objective signs and symptoms of anaphylaxis is required to ensure appropriate use of adrenaline
    • 

    corecore