Expert meeting report: towards a joint European roadmap to address the unmet needs and priorities of paediatric asthma patients on biologic therapy

Golebski, Korneliusz; Dankelman, Lente H.M.; Björkander, Sofia; Bønnelykke, Klaus; Brinkman, Paul; Deschildre, A.; Dijk, Yoni E. van; Fleming, Louise; Grigg, Jonathan; Hamelmann, Eckard; Hashimoto, Simone; Kabesch, Michael; Klevebro, Susanna; Zee, Anke‐Hilse Maitland‐van der; Merid, Simon Kebede; Nieto, Antonio; Niggel, Jakob; Nilsson, Caroline; Potočnik, Uroš; Roberts, Graham; Rusconi, Franca; Saglani, Sejal; Valente, Elisangela Santos; Drunen, Cornelis van; Wang, Gang; Vijverberg, Susanne

doi:10.1183/23120541.00381-2021

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…and available efficacy and safety data for the paediatric population are scarce. 231 In patients with CRSwNP, another chronic type 2 respiratory condition often coinciding with severe asthma, increased IL-5 levels in nasal secretions at baseline predicted clinical response to anti-IL-5 treatment with reslizumab. 232 However, clinical efficacy of anti-IL-5 targeting treatment has so far only been established for mepolizumab 233,234 in large number of patients with recurrent refractory CRSwNP with or without concomitant asthma, and consequently, this biologic has been implemented into concurrent treatment algorithms.…”

Section: Anti-il-5 Monoclonal Antibodies-mepolizumab Reslizumabmentioning

confidence: 99%

“…It should be pointed out that the children with severe asthma have been underreported in clinical trials with biologics (e.g. 1%–6% of the study populations with mepolizumab) and available efficacy and safety data for the paediatric population are scarce 231 . In patients with CRSwNP, another chronic type 2 respiratory condition often coinciding with severe asthma, increased IL‐5 levels in nasal secretions at baseline predicted clinical response to anti‐IL‐5 treatment with reslizumab 232 .…”

Section: Eosinophilia As Therapy‐guiding Tool For Targeted Anti‐eosin...mentioning

confidence: 99%

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Eosinophils—from cradle to grave

Jesenak,

Diamant,

Simon

et al. 2023

Allergy

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Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.

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Section: Anti-il-5 Monoclonal Antibodies-mepolizumab Reslizumabmentioning

confidence: 99%

Section: Eosinophilia As Therapy‐guiding Tool For Targeted Anti‐eosin...mentioning

confidence: 99%

Eosinophils—from cradle to grave

Jesenak,

Diamant,

Simon

et al. 2023

Allergy

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“…Although many studies have measured responses to different biologics, there are no universally accepted criteria for what constitutes response, and the absence of guidance on criteria is reported as a high priority research gap in both children and adults. 27,28 Evidence about responder definitions is critical for understanding the effectiveness of treatment for patients, clinicians and regulatory bodies, such as the European Medicines Agency (EMA) 29 and the Food and Drug Administration (FDA) 30 . Minimal Clinically Important Difference (MCID) 31 and Minimal Important Difference (MID) 32 are often used for assessing responses: these are defined as the smallest relevant within-person change or group differences between treatments, respectively.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Definitions of non-response and response to biological therapy for severe asthma: a systematic review

et al. 2023

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BackgroundBiologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined, and evaluated definitions of non-response and response to biologics for severe asthma.MethodsWe searched four bibliographic databases from inception to 15th March 2021 (PROSPERO: CRD42021211249).Two reviewers screened references, extracted data, assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). Modified GRADE approach and narrative synthesis were undertaken.ResultsThirteen studies reported three composite outcome measures, three measures of asthma symptoms, one asthma control and one quality of life. Only four were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10/17 (58.8%) were based on Minimal Clinically Important Difference (MCID) or Minimal Important Difference (MID) and 16/17 (94.1%) had high quality evidence. Results were limited by poor methodology for development process and incomplete reporting of psychometric properties. Most measures rated “very low” to “low” for quality of measurement properties and none met all quality standards.ConclusionThis is the first review to synthesize evidence about definitions of response to biologics for severe asthma. While high quality definitions are available, most are MCIDs or MIDs which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

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Factors influencing the initiation of biologic therapy in children with severe asthma: Results of the pediatric asthma noninvasive diagnostic approaches (PANDA) study

van Dijk,

Brandsen,

Hashimoto

et al. 2024

Pediatric Pulmonology

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Background & objectivesDespite the availability of biologics for severe pediatric asthma, real‐life studies reporting on drivers behind initiating biologics and their alignment with the Global Initiative for Asthma (GINA) recommendations are lacking.MethodsWe performed analysis within the pediatric asthma noninvasive diagnostic approaches study, a prospective cohort of 6‐ to 17‐year‐old children with severe asthma. Information was collected on demographic factors, symptom control, treatment, comorbidities, and diagnostic tests from medical records and questionnaires. We divided patients into “starters” or “nonstarters” based on the clinical decision to initiate biologics and performed multivariate logistic regression analysis to identify drivers behind initiating therapy. Additionally, we assessed patient suitability for biologics according to key factors in the GINA recommendations: Type 2 inflammation, frequency of exacerbations, and optimization of treatment adherence.ResultsIn total, 72 children (mean age 11.5 ± 3.0 years, 65.3% male) were included (13 starters). Initiation of biologics was associated with a higher GINA treatment step (adjusted odds ratio's [aOR] = 5.0, 95%CI 1.33–18.76), steroid toxicity (aOR = 21.1, 95%CI 3.73–119.91), frequency of exacerbations (aOR = 1.6, 95%CI 1.10–2.39), improved therapy adherence (aOR = 1.7, 95%CI 1.10–2.46), Caucasian ethnicity (aOR = 0.20, 95%CI 0.05–0.80), ≥1 allergic sensitization (aOR = 0.06, 95%CI 0.004–0.97), and allergic rhinitis (aOR = 0.13, 95%CI 0.03–0.65). Furthermore, steroid toxicity was identified as an important factor for deviation from the current recommendations on biologic prescription.ConclusionsWe identified multiple drivers and inhibitors for initiating biologics, and showed the clinical need for biologics in severe pediatric asthmatics suffering from steroid toxicity. These findings may help refine asthma management guidelines.

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Expert meeting report: towards a joint European roadmap to address the unmet needs and priorities of paediatric asthma patients on biologic therapy

Cited by 7 publications

References 39 publications

Eosinophils—from cradle to grave

Eosinophils—from cradle to grave

Definitions of non-response and response to biological therapy for severe asthma: a systematic review

Factors influencing the initiation of biologic therapy in children with severe asthma: Results of the pediatric asthma noninvasive diagnostic approaches (PANDA) study

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