Indacaterol 125micrograms/dose / Mometasone 260micrograms/dose inhalation powder capsules with device

Recent literature has shown that triple therapy is more effective than dual therapy for individuals with uncontrolled asthma. However, the comparative efficacy between different triple therapies remains unclear. The objective of this study was to determine the comparative efficacy of extra-fine single-inhaler medium-dose (MD) or high-dose (HD) of beclometasone/formoterol/glycopyrronium bromide (BDP/FOR/GLY) compared to other triple therapies in patients whose asthma remains uncontrolled with MD or HD inhaled corticosteroids and long-acting β2-agonists. A systematic literature review identified randomized control trials on adult patients with uncontrolled asthma. Two separate networks were constructed according to patients' previous inhaled-corticosteroid dosage. Network meta-analyses evaluated severe and moderate-to-severe exacerbations, pre-dose forced expiratory volume, and asthma control questionnaire responses at 52 (± 3) weeks. Among single-inhaler triple therapies, MD BDP/FOR/GLY significantly reduced the risk of severe exacerbations (RR [95% CrI] compared to MD fluticasone/umeclidinium/vilanterol: 0.65 [0.49, 0.89]), while HD BDP/FOR/GLY demonstrated an improved trend in reducing severe and moderate-to-severe exacerbations versus HD indacaterol acetate/glycopyrronium bromide/mometasone, fluticasone/umeclidinium/vilanterol, and salmeterol/fluticasone + tiotropium. HD BDP/FOR/GLY and HD BDP/FOR + tiotropium did not differ significantly. Compared to relevant single-inhaler triple therapies, MD and HD BDP/FOR/GLY are associated with a significant benefit or trend for improvement in terms of reducing the rate of severe and moderate-to-severe exacerbations.

Abstract licence: CC BY-NC-ND

BackgroundCombination inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) triple therapy is used in severe asthma. The clinical effect of high-dose (HD) vs medium-dose (MD) ICSs in ICS/LABA/LAMA is unclear.Research questionWhat is the clinical effect of HD compared with MD ICSs in ICS/LABA/LAMA treatment of asthma?Study design and methodsA systematic review and meta-analysis of randomized controlled trials including > 1 ICS dose in ICS/LABA/LAMA inhalers compared the outcomes of HD and MD ICS/LABA/LAMA. The primary outcome was the proportion of participants with ≥ 1 severe asthma exacerbations. Secondary outcomes included FEV1, the Asthma Control Questionnaire, emergency department visits, and hospital admissions. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations domains.ResultsThree randomized controlled trials (N = 3,804) were identified, comparing MD and HD ICS/LABA/LAMA containing fluticasone or mometasone. When comparing HD with MD ICS/LABA/LAMA for at least 1 severe exacerbation, the Peto OR was 0.81 (95% CI, 0.68-0.96; P = .01). This corresponds to a number needed to treat to prevent 1 severe exacerbation of 32.9. HD ICS/LABA/LAMA led to a higher FEV1 (mean difference, 50.8 mL; 95% CI, 29.5-72.2 mL; P P P = .07) or hospitalizations (Peto OR, 0.65; 95% CI, 0.33-1.29; P = .22) between HD and MD ICS/LABA/LAMA.InterpretationOur results show that HD compared with MD ICS/LABA/LAMA reduces the odds of a severe exacerbation by about 20%. This absolute risk reduction was modest but may be clinically relevant for patients with high baseline exacerbation rates and those with high type 2 inflammation. At both the individual and population level, the use of HD ICS/LABA/LAMA needs to be considered alongside the potential systemic side effects.Clinical trial registrationPROSPERO Registry; No.: CRD42025634340; URL: https://www.crd.york.ac.uk/prospero/.

Abstract licence: CC BY