OBJECTIVES: Severe asthma is a condition with a significant impact on quality of life and morbidity. Currently, omalizumab is the only immunobiologic agent covered by the Brazilian public health system for severe allergic asthma treatment. This study aims to compare the efficacy and safety of dupilumab, an IL-4/IL-13 signaling inhibitor, with omalizumab, an anti-IgE monoclonal antibody, in patients with severe allergic asthma to support coverage decisions.

METHODS: We searched Medline/Pubmed, EMBASE and Cochrane Central for double-blind randomized trials evaluating dupilumab or omalizumab as add-on therapy to long-acting beta2-agonists (LABA) and inhaled corticosteroids on patients with severe allergic asthma (defined as total IgE ≥30 IU/mL and sensitivity to ≥ 1 perennial allergens). Outcomes included exacerbation rate, forced expiratory volume in 1 second (FEV-1), and adverse events (AE) leading to treatment discontinuation. Meta-analysis for direct and indirect comparisons was performed using a frequentist approach, using random-effects model to account for heterogeneity. Risk of bias was assessed with RoB2. Certainty of evidence (CoE) was rated using GRADE framework for network meta-analysis.

RESULTS: We identified four studies assessing dupilumab and eight studies assessing omalizumab. To ensure proper comparability and minimize intransitivity, we included only studies with adequate blinding and using as co-interventions inhaled corticosteroids in combination with LABA. Dupilumab reduced exacerbation rate by 32% (relative risk [RR]:0.68; 95%CI: 0.54 to 0.88; low CoE due to risk of bias and indirectness in omalizumab) and increased FEV-1 compared to omalizumab (mean difference: 0,08L; 95%CI: 0.03 to 0.13; low CoE due to risk of bias and indirectness in omalizumab). No statistical difference was observed in AE leading to treatment discontinuation (RR:0.74; 95%CI: 0.28 to 1.93; moderate CoE due to imprecision).

CONCLUSIONS: In this indirect comparison, dupilumab was associated with lower exacerbation rates and greater improvements in lung function in patients with severe allergic asthma.