Clinical trial NCT05441059: Use of Nucala in Severe Asthma
Official title: Evaluation of Real World Use of Nucala in Severe Asthma Patients From the Severe Heterogenous Asthma Research Patient-centred Collaboration (SHARP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma Severe Persistent Uncontrolled
Lead sponsor: Frisius Medisch Centrum
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2022-07-01
Enrollment: 2100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will be selected from all patients who meet the criteria for inclusion in individual registries severe asthma registries. Within this severe asthma population, the study sample will include all patients who received at least one dose of mepolizumab.

Brief summary: The Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) is set up to harmonise severe asthma management across Europe and unravel underlying heterogeneity in a patient-centred way. Using data from national registries included in the SHARP network, this study aims to evaluate real-world use of Nucala, describe characteristics of patients prescribed with Nucala and evaluate the effectiveness of Nucala in clinically relevant endpoints.

Detailed description: The global prevalence of asthma is approximately 358 million people, of which an estimated 30 million patients live in Europe. Severe asthma is defined as asthma requiring treatment according to GINA steps 4-5 and is estimated to occur in 5-10% of the total asthma population (Chung 2014). Asthma and severe asthma are heterogeneous, and while there are a range of classifications, one such schema classified asthma as: (1) eosinophilic, (2) neutrophilic, (3) mixed, or (4) paucigranulocytic.

NUCALA (mepolizumab) is an IL-5 antagonist monoclonal antibody that was approved by the European commission in 2015 for add-on maintenance treatment of adult patients with severe refractory eosinophilic asthma. The license was expanded to paediatric patients (6-17 years old) in August 2018. Clinical efficacy was evaluated in multiple randomized, double-blind clinical trials. In the DREAM trial (NCT01000506), the rate of clinically significant exacerbations was 2.40 per patient per year among patients receiving placebo versus 1.24 in the 75 mg IV mepolizumab group, a 48% (95% CI 31-61%) reduction. In the MENSA trial (NCT01691521), the rate of clinically significant exacerbations was 1.74 per patient per year among patients receiving placebo versus 0.83 in the sub-cutaneous 100 mg mepolizumab group, a 53% (95% CI 36-65%) reduction. Furthermore, in the SIRIUS trial (NCT01691508), the median daily prednisone dose at weeks 20-24 was 10.0 mg among patients receiving placebo versus 3.1 mg for patients receiving 100 mg of mepolizumab and mepolizumab provided a 2.39 (95% CI 1.25-4.56) times greater odds for a reduction in oral glucocorticoid dose from baseline in the mepolizumab group compared with placebo. Additionally, the MUSCA trial (NCT02281318) found that mepolizumab significantly improved health-related quality of life in patients with severe eosinophilic asthma.

The high internal validity of the randomized clinical trials has allowed the treatment efficacy of Nucala to be reliably determined in patients with severe eosinophilic asthma. However, the strict inclusion and exclusion criteria which are necessary in clinical trials produce data from a selected, homogeneous population which may not be representative of the wider population who may receive treatments in routine practice.

Real world evaluation of mepolizumab use will help in understanding characteristics of patients from different European countries receiving these therapies, treatment patterns, and effectiveness on clinical endpoints as limited information exists in real world settings in Europe following the availability of mepolizumab to patients.

The Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) is set up to harmonise severe asthma management across Europe and unravel underlying heterogeneity in a patient-centred way. Using data from national registries included in the SHARP network, this study aims to evaluate real-world use of Nucala, describe characteristics of patients prescribed with Nucala and evaluate the effectiveness of Nucala in clinically relevant endpoints.

Eligibility criteria: Inclusion Criteria:

1) Initiated on mepolizumab for treatment of asthma.

Exclusion Criteria:

1) Participation in an interventional clinical trial in which the treatment regimen and/or monitoring is dictated by a protocol in the study observation period.

Primary outcomes:
measure: The change from baseline rate of annualized asthma exacerbations 1 year after initiation with mepolizumab
timeFrame: 1 year
measure: The change from baseline maintenance oral corticosteroid dose (mg/day, predinisone equivalents) 1 year after initiation with mepolizumab
timeFrame: 1 year
Secondary outcomes:
measure: Clinical and patient reported measures of asthma control (ACT and/or ACQ) in the periods before and after initiation with mepolizumab
timeFrame: 1 year
measure: The change from baseline measures of healthcare utilisation (number of hospitalisations and emergency department visits) 1 year after initiation with mepolizumab
timeFrame: 1 year
measure: Proportion of patients who stop mepolizumab after 1 year after initiation
timeFrame: 1 year
Other outcomes:
Locations:
city: Leeuwarden
country: Netherlands
facility: Medical Centre Leeuwarden
state: Friesland
Study officials:
References:
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citation: Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, Trevor JL, Magnan A, Ten Brinke A. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017 May;5(5):390-400. doi: 10.1016/S2213-2600(17)30125-X. Epub 2017 Apr 5.
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