Evaluation of Mepolizumab for Achieving Clinical Remission in Patients with Severe Asthma: A Prospective, Real-World Interventional Study

The primary objective of this study is to describe the proportion of patients with **severe asthma** who achieve clinical remission at 12 months, specifically in the principal stratum of patients adherent to **mepolizumab** (Nucala). This objective is clinically relevant as achieving clinical remission can significantly improve patient outcomes and quality of life by reducing the burden of severe asthma symptoms and the need for additional medication.

Secondary objectives include: - Summarizing the rate of clinically significant asthma exacerbations over the follow-up period in patients adherent to Nucala. - Describing the proportion of patients achieving oral corticosteroid (OCS) sparing and 3-component clinical remission at 12 months. - Evaluating the change from baseline in health-related quality of life (HRQoL) in the principal stratum of patients adherent to Nucala. These secondary objectives aim to provide a comprehensive understanding of the broader impacts of mepolizumab on patient health and treatment adherence.

The clinical trial involves a total of **166 participants** diagnosed with **severe asthma**. The study population includes both male and female adults aged 18 years or older. Participants were selected based on a confirmed asthma diagnosis and a physician's decision to initiate treatment with NUCALA. The trial includes individuals with a predicted FEV1 of 60% or greater and no more than four exacerbations per year, as confirmed by a physician. All participants provided written informed consent. The trial population encompasses a vulnerable group, indicating special considerations in the study design. Lifestyle factors such as diet, physical activity, or habits were not specified in the available data.

The clinical trial is designed to evaluate the effect of **mepolizumab** on achieving clinical remission in participants with severe asthma. This is a prospective, real-world, interventional study with a randomized, double-blind, controlled design. The trial is expected to last until July 31, 2026, with recruitment starting on May 1, 2024. Participants will be involved for a maximum treatment period of 24 months, receiving a maximum daily dose of 100 mg of Nucala, administered via subcutaneous injection. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress, and an end-of-study visit to assess outcomes.

Inclusion criteria for the study require participants to be adults aged 18 years or over, with a confirmed diagnosis of asthma and a physician's decision to initiate treatment with Nucala. Participants must have a predicted FEV1 of at least 60% and no more than four exacerbations per year. Written informed consent is also required. The primary endpoint is the proportion of patients achieving a 4-component clinical remission at 12 months, with secondary endpoints including clinically significant asthma exacerbations, oral corticosteroids sparing remission, and changes in the mini-AQLQ score from baseline to 12 months.

Participants may be terminated early from the study if they experience adverse effects, fail to adhere to the treatment protocol, or withdraw consent. The study is categorized as a low-intervention clinical trial, as the medicine of interest, Nucala, is authorized for use and administered within the terms of its marketing authorization. The study interventions include lung function assessments via spirometry and additional patient-reported outcomes. These assessments are generally administered in routine clinical practice, although the timing may vary in relation to Nucala treatment.

The clinical trial involves the administration of **Nucala** (mepolizumab), a monoclonal antibody, as the experimental medication. Nucala is provided in two pharmaceutical forms: a solution for injection in a pre-filled pen and a solution for injection in a pre-filled syringe. Each form contains 100 mg of mepolizumab. The medication is administered via **subcutaneous injection**. The maximum daily dose is 100 mg, with a total maximum dose of 2500 mg over the course of the study. The treatment period extends up to 24 months. The administration schedule is designed to ensure participant compliance, with regular monitoring to assess adherence to the dosing regimen.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the effects of mepolizumab in achieving clinical remission in participants with severe asthma. The trial is structured to monitor the proportion of patients achieving clinical remission at 12 months, specifically in those adherent to Nucala. Compliance is assessed through scheduled follow-ups and adherence checks to ensure the integrity of the trial outcomes.

The efficacy of the clinical trial will be assessed by evaluating the achievement of clinical remission in participants with severe asthma treated with **mepolizumab**. The primary endpoint is the proportion of patients achieving a 4-component clinical remission at 12 months, with results expressed as a proportion and 95% confidence interval. Secondary endpoints include the incidence of clinically significant asthma exacerbations, exacerbations leading to hospitalization or emergency room visits, achieving oral corticosteroids sparing remission, achieving 3-component clinical remission, and changes in the 15-item mini-Asthma Quality of Life Questionnaire (mini-AQLQ) overall score from baseline to 12 months.

Data collection will involve patient-reported outcomes and clinical assessments, including spirometry to assess lung function. Additional assessments such as the Asthma Control Test (ACT), Asthma Control Questionnaire-6 (ACQ-6), mini-AQLQ, Chronic Asthma Assessment Test (CAAT), and Work Productivity and Activity Impairment Questionnaire: Asthma (WPAI-Asthma) will be conducted as per protocol. These assessments are generally administered in routine clinical practice, although the timing of administration in relation to Nucala treatment may vary. The study is designed as a low-intervention clinical trial, with the medicine of interest, Nucala, being used within the terms of its marketing authorization.