Table 4. Current evidence on LAMA/LABA FDCs in Chinese patients.

Study	Population	Design	Comparators	Reported outcomes
GLY/IND
Zhong et al., 2015 (LANTERN)	744 Chinese patients with moderate to severe COPD with a history of ≤1 exacerbation in the previous year	26-week MC, RCT, DB, double-dummy, PG study	SFC 50/500 μg b.i.d.	Lung function: trough FEV1, FEV1 AUC0–4h at day 1 and week 26, peak FEV1 at day 1 and week 26, peak FVC (taken over the first 4 hours) was significantly greater with GLY/IND. Health status: the improvements in the SGRQ total scores and total CAT scores in 2 groups are similar. Dyspnea: the improvements in the TDI focal score in 2 groups are similar. Exacerbations: annual moderate or severe exacerbations rate was significantly lower in GLY/IND group than in SFC group. Safety and tolerance: fewer AEs in the patients treated with GLY/IND. The total number of AEs leading to hospitalization in SFC group was almost double of that in GLY/IND group
Wedzicha et al., 2017 (FLAME)	510 Asian patients with moderate to very severe COPD and ≥1 exacerbation in the previous year (316 from the Chinese patients)	52-week, MC, RCT, DB, double-dummy, PG, noninferiority, actively controlled study	SFC 50/500 µg b.i.d.	Lung function: improvement in pre-dose trough FEV1 was significantly greater with GLY/IND than with SFC. Health status: over the 52-week treatment period, the improvement in the SGRQ-C total score was greater with GLY/IND than with SFC. Dyspnea: –. Exacerbations: GLY/IND significantly reduced the rate of moderate or severe exacerbations, and prolonged the time to the first moderate or severe exacerbation. Safety and tolerance: the incidences of AEs in 2 groups were similar. The pneumonia incidence was numerically lower in the GLY/IND group
UMEC/VI
Zheng et al., 2015	739 patients with an established clinical history of COPD (467 Chinese patients)	24-week, phase III, MC, RDBPC, PG study	UMEC/VI 125/25 μg, placebo	Lung function: trough FEV1 and trough FVC on day 169 were both significantly greater in the UMEC/VI groups vs. placebo. Health Status: UMEC/VI groups had a significantly improved SGRQ total score on day 84 and clinically meaningful improvements in the mean CAT scores vs. placebo from baseline on day 168. Dyspnea: TDI scores for the UMEC/VI groups were significantly greater vs. placebo on day 168. Exacerbations: UMEC/VI 125/25 μg reduced the risk of exacerbation vs. placebo, although the same effect was not observed for UMEC/VI 62.5/25 μg. Safety and Tolerance: Incidences of AEs were similar across treatment groups
TIO/OLO
Wang et al., 2020	12 Chinese patients with moderate to severe COPD	3-week, single site, OL, phase Ib clinical study	–	Lung function: –. Health status: –. Dyspnea: –. Exacerbations: –. Safety and tolerance: TIO/OLO combination was well-tolerated; all AEs were mild
Bai et al., 2019 (TONADO)	548 Chinese patients with moderate to very severe COPD	52-week, DB, PG, actively controlled, RCT, phase III studies (TONADO 1+2)	TIO 5 μg, OLO 5 μg	Lung function: trough FEV1 and adjusted mean FEV1 AUC0–3 h were significantly greater with TIO/OLO than with TIO or OLO monotherapy. Health status: TIO/OLO significantly improved SGRQ scores compared with OLO monotherapy. Dyspnea: –. Exacerbations: –. Safety and tolerance: the safety profile of TIO/OLO was comparable with that of monotherapy over 52 weeks. AEs were not increased in the TIO/OLO group compared with the monotherapy groups
GFF
Chen et al., 2020 (PINNACLE-4)	466 Chinese patients with moderate to very severe COPD	RDBPC, PG, phase III study (PINNACLE-4)	GP 18 µg, FF 9.6 µg, placebo	Lung function: the change from baseline in the pre-dose trough FEV1 at week 24 was significantly greater with GFF than monotherapy or placebo. Health status: the estimated difference from baseline in the SGRQ score at week 24 was lower with GFF than placebo. Dyspnea: TDI focal score over 24 weeks showed a clinically meaningful improvement with GFF compared to the placebo. Exacerbations: the risk of a moderate or severe exacerbation was numerically lower in the GFF group than in the GP, FF, and placebo groups. GFF reduced CID. Safety and tolerance: AE rates were similar across all active treatment groups and slightly higher in the placebo group

LAMA, long-acting muscarinic antagonist; LABA, long-acting β agonist; FDC, fixed-dose combination; GLY/IND, glycopyrronium/indacaterol; UMEC/VI, umeclidinium/vilanterol; GFF, glycopyrrolate/formoterol fumarate; TIO/OLO, tiotropium/olodaterol; ACL/FF, aclidinium/formoterol; TIO/FF, tiotropium/formoterol; AEs, adverse events; CAT, COPD Assessment Test; CID, clinically important deterioration; FEV₁, forced expiratory volume in 1 second; FEV₁ AUC_0–4h, FEV₁ area under the curve from 0–4 h; FVC, forced vital capacity; TDI, Transition Dyspnea Index; SFC, salmeterol/fluticasone; SGRQ, St. George’s Respiratory Questionnaire; SGRQ-C, SGRQ for COPD; vs., versus; –, no related content; MC, multi-centre; DB, double blind; RCT, randomized controlled trial; PG, parallel group; MNC, multinational; OL, open-label; RDBPC, randomized, double-blind, placebo-controlled.