Dupilumab in the Treatment of Asthma

Grey, Alice; Katelaris, Constance H.

doi:10.2217/imt-2019-0008

Cited by 16 publications

(13 citation statements)

References 38 publications

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“…Importantly, these data suggest that Th2 inhibition (Barranco et al, 2017) might potentially offer protection against COVID-19 severe symptoms, provided that there are minimal effects on Th1. Our findings may help guide personalized medicine decisions, particularly in patients that are eligible to receive Th2 inhibitors such as those with asthma or other atopic conditions (Barranco et al, 2017;Grey and Katelaris, 2019;Guttman-Yassky et al, 2019). However, this can truly be validated through clinical trials and longitudinal studies.…”

Section: Discussionmentioning

confidence: 91%

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

et al. 2021

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A major component of COVID-19 severe respiratory syndrome is the patient’s immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p < 0.001), as well as in the asthmatic strata only (p < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.

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Section: Discussionmentioning

confidence: 91%

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

et al. 2021

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“…The use of dupillumab warrants more prospective studies in IgG4-RD. Dupilumab was also recently approved for treatment of moderate to severe asthma both in adolescents and adults (131). Kasaian et al created a recombinant bifunctional IL-4/IL-13 antagonist that in a mouse of model of asthma reduced not only IL-4-dependent increase in serum IgE levels but also IL-13dependent airway hyper-responsiveness and lung inflammation (132).…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

“…The use of dupillumab warrants more prospective studies in IgG4-RD. Dupilumab was also recently approved for treatment of moderate to severe asthma both in adolescents and adults ( 131 ).…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

Allergic Aspects of IgG4-Related Disease: Implications for Pathogenesis and Therapy

et al. 2021

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IgG4-related disease (IgG4-RD) is a rare systemic fibroinflammatory disease frequently associated with allergy. The pathogenesis of IgG4-RD is poorly understood, and effective therapies are limited. However, IgG4-RD appears to involve some of the same pathogenic mechanisms observed in allergic disease, such as T helper 2 (Th2) and regulatory T cell (Treg) activation, IgG4 and IgE hypersecretion, and blood/tissue eosinophilia. In addition, IgG4-RD tissue fibrosis appears to involve activation of basophils and mast cells and their release of alarmins and cytokines. In this article, we review allergy-like features of IgG4-RD and highlight targeted therapies for allergy that have potential in treating patients with IgG4-RD.

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“…Este inmunobiológico fue aprobado en 2018 por la FDA para su uso en pacientes mayores de 12 años con asma eosinofílica grave esteroide dependiente 4 . La eficacia de dupilumab ha sido comprobada en ensayos clínicos controlados, mostrando una disminución en las exacerbaciones de asma (que es mayor en sujetos con un recuento de eosinófilos mayor o igual a 300 células/microlitro y con FENO mayor o igual a 25 ppb), una mejoría en la función pulmonar con incremento del VEF1, disminución en la necesidad de esteroides orales en un 70 % (incluso con posibilidad de discontinuarlos) y una mejora en los puntajes clínicos del control de síntomas 17 . Debe ser administrado en dosis de 400 a 600 mg por vía subcutánea, seguido de 200 o 300 mg cada 2 semanas.…”

Section: Dupilumabunclassified

“…Los efectos adversos más frecuentes con su uso son reacciones en el sitio de la administración (en 18% de los pacientes) e hipereosinofilia (en 4 a 14% de los pacientes). La hipereosinofilia es transitoria y asintomática en la mayoría de los pacientes, aunque algunos presentan síntomas de neumonitis y miositis 17,18 .…”

Section: Dupilumabunclassified

Estado actual del uso de medicamentos biológicos en asma grave

González¹,

Saranz²,

Lozano³

et al. 2020

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Asma es una enfermedad heterogénea que se manifiesta con diferentes fenotipos y endotipos defisiopatología compleja. El asma grave resistente al tratamiento con altas dosis de esteroides inhalatorioses una entidad infrecuente pero que plantea un gran desafío para el médico. Los progresos en losconocimientos de la fisiopatogenia del asma han permitido el desarrollo de nuevas terapias coninmunobiológicos que permiten una terapia más individualizada en el contexto de la medicina de precisión.La mayoría de estas nuevas terapias han sido desarrolladas para el asma T2 alta, principalmente eosinofílica,pero son menos los desarrollos para el asma T2 baja, cuyos mecanismos no están completamentedilucidados. Esta revisión intenta recopilar las más recientes evidencias acerca del uso de medicamentosbiológicos en el asma grave, con especial énfasis en sus mecanismos de acción, indicaciones, eficaciaclínica y posibles efectos adversos.

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Dupilumab in the Treatment of Asthma

Cited by 16 publications

References 38 publications

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

Allergic Aspects of IgG4-Related Disease: Implications for Pathogenesis and Therapy

Estado actual del uso de medicamentos biológicos en asma grave

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