Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in Chinese Patients with COPD: A Subgroup Analysis of KRONOS

Abstract

Introduction: This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, doubleblind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Methods: Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 lg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 lg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 lg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 lg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV 1) over weeks 12-24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint.

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

“…The nature and incidence of TEAEs observed in KRO-NOS was consistent with those observed in ETHOS, with the tolerability profile of budesonide/glycopyrronium/formoterol in the Japanese [25] and Chinese [26] subpopulations being generally similar to that of the overall population in KRONOS.…”

“…In subgroup analyses of ETHOS and KRONOS, some of which were post hoc, budesonide/glycopyrronium/formoterol generally improved lung function (FEV 1 AUC 0–4 and morning pre-dose trough FEV 1 responses) compared with glycopyrronium/formoterol and budesonide/formoterol irrespective of sex, age, race, COPD exacerbation history, CAT score, prior ICS use, bronchodilator reversibility and postbronchodilator FEV 1 [ 3 , 4 , 24 – 26 , 28 , 29 , 32 ]. Patients with elevated eosinophil counts at baseline tended to benefit more with budesonide/glycopyrronium/formoterol relative to glycopyrronium/formoterol and budesonide/formoterol, with greater benefits observed in patients with baseline eosinophil counts of > 150 cells/mm 3 than those with < 150 cells/mm 3 [ 17 , 18 , 24 ].…”

“…In subgroup analyses of ETHOS and KRONOS, some of which were post hoc, budesonide/glycopyrronium/formoterol generally reduced moderate or severe COPD exacerbation rates compared with glycopyrronium/formoterol and budesonide/formoterol irrespective of sex, age, race, region, COPD exacerbation history, CAT score, prior ICS use, bronchodilator reversibility and postbronchodilator FEV 1 [3,4,17,[24][25][26][27][28][29][30][31][32]. Moreover, benefits were seen across a broad range of baseline eosinophil counts, but tended to increase as eosinophil counts increased [17,18,24].…”

Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial

“…≥ 1.5% in either group of the overall population for adverse events and ≥ 0.5% in either group of the overall population for serious adverse events, treatment-related adverse events, and adverse events leading to study drug discontinuation. BDP beclometasone dipropionate, FF formoterol fumarate, G glycopyrronium, BUD budesonide, COPD chronic obstructive pulmonary disease a non-statistically significant 49% reduction in moderate/severe exacerbation rate [19]. Our results are broadly consistent with these, but with a much larger sample size, and with a statistically significant reduction in the rate of moderate/severe exacerbations.…”

“…One previous study evaluated the efficacy of tiotropium plus BUD/FF in five eastern Asian areas, in which triple therapy improved bronchodilation and health status compared with tiotropium alone, with a 40.7% reduction in exacerbation rate (of note, patients in the tiotropium group were not permitted ICS) [ 17 ]. Subgroup analyses in patients from China have been published from two other single-inhaler triple therapy studies: in FULFIL, triple therapy with fluticasone furoate/umeclidinium/vilanterol improved bronchodilation compared with BUD/FF, with numerical improvements in health status and exacerbation rate [ 18 ], whereas in KRONOS BUD/glycopyrrolate/FF improved bronchodilation and health status versus BUD/FF, with a non-statistically significant 49% reduction in moderate/severe exacerbation rate [ 19 ]. Our results are broadly consistent with these, but with a much larger sample size, and with a statistically significant reduction in the rate of moderate/severe exacerbations.…”