Assessment of Long-term Dupilumab Effects on Acetylsalicylic Acid Intolerance in Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease

The primary objective of this study is to evaluate the **long-term effect** of **Dupilumab** on patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), with a particular emphasis on its impact on **acetylsalicylic acid (ASA) intolerance**. The study aims to determine whether there is an increase in the number of patients who develop tolerance to salicylic acid following treatment with Dupilumab, compared to their tolerance levels before treatment and six months after treatment initiation. This is clinically relevant as improving ASA tolerance in N-ERD patients could significantly enhance their quality of life and reduce the risk of respiratory complications associated with ASA intolerance.

The clinical trial focuses on individuals diagnosed with **non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD)**. The study population includes both male and female participants, with an age range that corresponds to categories 3 and 4, typically encompassing adults and older adults. Participants are generally in good health, as the trial does not target a vulnerable population. The total number of participants is not specified, as the sponsor has not provided this information. Selection criteria include previous participation in study EK 1044/2020, current therapy with Dupilumab, and the provision of signed and dated informed consent. Lifestyle factors such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is designed to evaluate the long-term effects of **Dupilumab** on patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), with a particular focus on salicylic acid tolerance. This study is a low-intervention trial, as participants are already undergoing treatment with Dupilumab, which is administered in accordance with its marketing authorization. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know who is receiving the treatment or placebo, thus minimizing bias. The trial is expected to last until March 31, 2026, with recruitment starting on April 1, 2025.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as previous participation in study EK 1044/2020, signed informed consent, and current therapy with Dupilumab. Follow-up visits will be scheduled to monitor the primary endpoint, which involves assessing tolerated aspirin dose levels at various dosages compared to baseline and six months into treatment. Secondary endpoints include measurements of serum ECP, total IgE, allergen-specific IgE, tryptase, peripheral blood eosinophils, and other biomarkers. The end-of-study visit will conclude the trial, summarizing the long-term effects of Dupilumab on aspirin tolerance and other secondary outcomes.

Participant involvement is expected to last for the duration of the trial, with a maximum treatment period of 60 months. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation where continued participation is deemed not in the best interest of the participant. The trial aims to provide valuable insights into the long-term management of N-ERD with Dupilumab, contributing to the understanding of its effects on aspirin intolerance and related mechanisms.

The clinical trial involves the administration of **Dupixent** (dupilumab), a **solution for injection** in a pre-filled syringe. Dupixent is provided at a concentration of 300 mg per syringe. The pharmaceutical form is a solution intended for **subcutaneous injection**. The dosing regimen for this trial specifies a maximum daily dose of 300 mg, with a treatment period extending up to 60 days. Dupilumab is a protein-based therapeutic agent, classified under the ATC code D11AH05, and is produced by Sanofi Winthrop Industrie. The administration of Dupixent is designed to evaluate its long-term effects on patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), particularly focusing on salicylic acid tolerance.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is structured to monitor participant compliance with the dosing schedule, ensuring adherence to the prescribed regimen. The primary objective is to assess the impact of Dupilumab on acetylsalicylic acid intolerance in the target patient population, with the expectation of improved tolerance rates post-treatment.

The efficacy of Dupilumab in patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) will be assessed through a series of primary and secondary endpoints. The primary endpoint involves evaluating the tolerated aspirin dose levels, tested at various dosages (62.5 mg, 125 mg, 250 mg, and 500 mg), compared to the tolerated dosages before and six months into Dupilumab treatment. This assessment aims to determine any improvement in **acetylsalicylic acid** tolerance over the course of the treatment.

Secondary endpoints will include a comprehensive analysis of several biomarkers and clinical parameters. These include serum eosinophil cationic protein (ECP), total immunoglobulin E (IgE), allergen-specific IgE, tryptase, and peripheral blood eosinophils. Additionally, allergenic sensitization will be assessed through skin prick and blood tests. Other parameters include olfactory performance, prostaglandin levels in urine, cytokine patterns in nasal secretions, inflammatory cytokine patterns at mRNA levels, and nasal microbiome composition. Patient-reported outcomes will be measured using tools such as the Total Polyp Score (TPS), Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT-22), Asthma Control Test (ACT), and Asthma Control Questionnaire (ACQ).