Anti-IL-5 therapies for asthma

Farne, Hugo; Wilson, Amanda; Milan, Stephen J; Banchoff, Emma; Yang, Freda; Powell, Colin

doi:10.1002/14651858.cd010834.pub4

Cited by 14 publications

(7 citation statements)

References 290 publications

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“…In this study of children with asthma living in urban, high-poverty areas, participation in a housing mobility intervention was associated with statistically significant reductions in asthma exacerbations and maximum symptom days. The magnitude of reduction of exacerbations associated with moving was greater than that observed for individual- and household-level interventions for asthma in racialized populations, larger than the effect of inhaled corticosteroids (43% reduction in exacerbation rate in the Childhood Asthma Management Program), and similar to that observed for the effect of biologic agents (≥50%) …”

Section: Discussionsupporting

confidence: 78%

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

Pollack,

Roberts,

Peng

et al. 2023

JAMA

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ImportanceStructural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact.ObjectiveTo examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors.Design, Setting, and ParticipantsCohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores.ExposureMoving to a low-poverty neighborhood.Main OutcomesCaregiver-reported asthma exacerbations and symptoms.ResultsAmong 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (&gt;20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of −6.8 percentage points (95% CI, −11.9% to −1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of −2.37 days (95% CI, −3.14 to −1.59; P &lt; .001). Results remained significant in propensity score–matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations.Conclusions and RelevanceChildren with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

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Section: Discussionsupporting

confidence: 78%

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

Pollack,

Roberts,

Peng

et al. 2023

JAMA

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“…Anti-IL-5-(R): Mepolizumab und Reslizumab (monoklonale, gegen Interleukin-5 gerichtete Antikörper) stehen für ≥ 6 Jahre bzw. ≥ 18 Jahre alte Patienten mit schwergradigem eosinophilen Asthma zur Verfügung, Benralizumab (ein gegen die Alphakette des Interleukin-5-Rezeptors gerichteter Antikörper) ist für ≥ 18 Jahre alte Patienten mit schwergradigem eosinophilen Asthma zugelassen 256 . Mepolizumab und Reslizumab binden zirkulierendes freies Interleukin-5 und führen so zu einer effektiven Inhibition der Reifung und Aktivierung eosinophiler Granulozyten, mit konsekutiver Reduktion der Zahl eosinophiler Granulozyten im peripheren Blut und in der Lunge.…”

Section: Medikamentöse Therapieunclassified

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

et al. 2023

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ZusammenfassungDas Management von Asthma hat sich in den letzten Jahrzehnten fundamental gewandelt. Die vorliegende Leitlinie zur Diagnostik und Therapie von Asthma wurde für pneumologisch tätige Fachärztinnen und Fachärzte entwickelt, welche detaillierte und evidenzbasierte Informationen zu den neuen diagnostischen und therapeutischen Optionen von Asthma benötigen. Die Leitlinie zeigt die neue Bedeutung der Biomarker, insbesondere der Bluteosinophilen und des exhalierten NO (FeNO), in den diagnostischen Algorithmen von Asthma. Als erste Asthma-Leitlinie weltweit benennt die vorliegende Leitlinie die nachhaltige Symptomprävention und die Asthma-Remission als Asthma-Therapieziele, welche durch den Einsatz individuell angepasster, krankheitsmodifizierender Medikamente (wie inhalative Steroide, Allergenimmuntherapie oder Biologika) erreicht werden können. Die zentrale Bedeutung der Behandlung von typischen Asthma-Komorbiditäten wird zudem betont. Schließlich wird auch auf besondere Herausforderungen im Asthma-Management eingegangen, wie bspw. die Therapie von Asthma in der Schwangerschaft, die Behandlung von schwerem Asthma oder die Diagnostik und Therapie von arbeitsbedingten Asthma-Formen.

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“…Based on the IL‐5‐TCR signalosome hypothesis, it would be reasonable to evaluate therapies that more precisely interfere with the TCR signalosome, such as, for example, JAK inhibitors 86 Anti‐IL‐5/anti IL‐5R therapy has proven effective in severe allergic diseases, 87 and improvement has also been observed in most DRESS patients with eosinophilia. This suggests a significant role of IL‐5 in this form of DRESS 84 …”

Section: Discussionmentioning

confidence: 99%

“…84,85 Based on the IL-5-TCR signalosome hypothesis, it would be reasonable to evaluate therapies that more precisely interfere with the TCR signalosome, such as, for example, JAK inhibitors. 86 • Anti-IL-5/anti IL-5R therapy has proven effective in severe allergic diseases, 87 symptoms. Indeed, presence of eosinophilia in DHR was linked to a more severe clinical course.…”

Section: Summary and Con Clus Ionmentioning

confidence: 99%

Drug hypersensitivity and eosinophilia: The decisive role of p‐i stimulation

Pichler

Thoo

Yerly

2023

Allergy

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Eosinophilia is a common finding in drug hypersensitivity reactions (DHR). Its cause is unclear, as neither antigen/allergen‐driven inflammation nor clonal expansion is involved. Most delayed‐DHRs are due to p‐i (pharmacologic interaction of drugs with immune receptors). These are off‐target activities of drugs with immune receptors that result in various types of T‐cell stimulation, some of which involve excessive IL‐5 production. Functional and phenotypic studies of T‐cell clones and their TCR‐transfected hybridoma cell lines revealed that some p‐i‐induced drug stimulations occur without CD4/ CD8 co‐receptor engagement. The CD4/CD8 co‐receptors link Lck (lymphocyte‐specific protein tyrosine kinase) and LAT (linker for activation of T cells) to the TCR. Alteration of Lck or LAT can result in a TCR signalosome with enhanced IL‐5 production. Thus, if a more affine TCR‐[drug/peptide/HLA] interaction allows bypassing the CD4 co‐receptor, a modified Lck/LAT activation may lead to a TCR signalosome with elevated IL‐5 production. This “IL‐5‐TCR‐signalosome” hypothesis could also explain eosinophilia in superantigen or allo‐stimulation (graft‐versus‐host disease), in which evasion of CD4/CD8 co‐receptors has also been described. It may open new therapeutic possibilities in certain eosinophilic diseases by directly targeting the IL‐5‐TCR signalosome.

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Anti-IL-5 therapies for asthma

Cited by 14 publications

References 290 publications

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

Drug hypersensitivity and eosinophilia: The decisive role of p‐i stimulation

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