Journal of Asthma and Allergy (May 2022)
Potential Drawbacks of ICS/LABA/LAMA Triple Fixed-Dose Combination Therapy in the Treatment of Asthma: A Quantitative Synthesis of Safety Profile
Abstract
Paola Rogliani,1 Francesco Cavalli,1 Alfredo Chetta,2 Mario Cazzola,1 Luigino Calzetta2 1Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, ItalyCorrespondence: Paola Rogliani, Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy, Email [email protected]: Inhaled corticosteroid/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) fixed-dose combination (FDC) is currently recommended as controller option at asthma Step 4 and as preferred treatment at asthma Step 5, but no research investigated the potential drawbacks of this therapeutic option in a large asthmatic population. Thus, the aim of this study was to quantify the potential drawbacks of triple FDC therapy in asthma.Methods: A pairwise meta-analysis was performed according to PRISMA-P guidelines to assess the risk of overall serious adverse events (SAEs), cardiovascular SAEs, and pneumonia reported as SAE in asthmatic patients treated with ICS/LABA/LAMA FDC vs ICS/LABA FDC. A pooled analysis was performed to calculate the frequency of SAEs.Results: Data from 7204 asthmatic patients were extracted from the CAPTAIN, IRIDIUM, TRIMARAN, and TRIGGER studies. Triple FDC vs ICS/LABA FDC did not increase the risk of total SAEs (RR 0.99 95% CI 0.83– 1.18) and cardiac SAEs (RR 0.74 95% CI 0.39– 1.40), whereas the sensitivity analysis performed to resolve heterogeneity resulted in increased risk of vascular SAEs (RR 3.23 95% CI 1.05– 9.90, P< 0.05). The level of ICS dose did not modulate the risk of pneumonia, in any case pneumonia was the most frequent SAE (0.57%). These results were not affected by significant risk of bias.Conclusion: Triple FDC is a safe pharmacological therapy in severe asthmatic patients; it is characterized by a favourable safety profile and few potential drawbacks, namely, the increased risk of vascular SAEs, that certainly are worthy of future investigations.Keywords: asthma, cardiovascular, meta-analysis, pneumonia, safety, triple combination
