Pneumologie 2019; 73(S 01)
DOI: 10.1055/s-0039-1678047
Posterbegehung (P05) – Sektion Klinische Pneumologie
Asthma 2019
Georg Thieme Verlag KG Stuttgart · New York

Risk of a severe exacerbation following higher reliever use: post-hoc analysis of SYGMA 1 in mild asthma

P OʼByrne
1   Firestone Institute for Respiratory Health; St Josephʼs Healthcare and Department of Medicine; Michael G. Degroote School of Medicine
,
JM Fitzgerald
2   The Lung Centre, Gordon and Leslie Diamond Health Care Centre; University of British Columbia
,
E Bateman
3   Department of Medicine, University of Cape Town, Division of Pulmonology
,
PJ Barnes
4   Airway Disease Division, National Heart & Lung Institute, Imperial College
,
N Zhong
5   State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases
,
P Gustafson
6   Astrazeneca
,
R Lamarca
6   Astrazeneca
,
M Puu
6   Astrazeneca
,
C Keen
6   Astrazeneca
,
M Wang
6   Astrazeneca
,
HK Reddel
7   Woolcock Institute of Medical Research, University of Sydney
› Author Affiliations
Further Information

Publication History

Publication Date:
19 February 2019 (online)

Also available at
 

Introduction In mild asthma, as-needed budesonide/formoterol (BUD/FORM) reduces long-term severe exacerbation risk vs. terbutaline as-needed, with similar reduction as maintenance BUD + terbutaline as-needed. In a post-hoc analysis of SYGMA 1 (NCT02149199; OʼByrne et al. NEJM 2018;378(20):1865 – 1876) we examined the short-term risk of a severe exacerbation after a single day with various levels of reliever use, comparing terbutaline as-needed, BUD/FORM as-needed, and maintenance BUD + terbutaline as-needed.

Methods In the SYGMA 1 study, 3836 patients with mild asthma were randomised to placebo twice daily (bid) + terbutaline 0.5 mg as-needed, placebo bid + BUD/FORM 200/6 µg as-needed, or maintenance BUD 200 µg bid + terbutaline as-needed. For patients with > 2, > 4, > 6 or > 8 reliever inhalations on any day, the proportions who had a severe exacerbation during the next 21 days were compared.

Results The proportion of patients with > 4, > 6 or > 8 as-needed inhalation use days was lower with BUD/FORM as-needed vs. terbutaline as-needed and maintenance BUD + terbutaline as-needed, with reduced risk of severe exacerbation during the next 21 days vs. terbutaline as-needed ([Fig. 1]; [Table 1]). The safety of BUD/FORM as-needed was consistent across all inhalation groups, with no new safety findings.

Zoom Image
Kaplan-Meier plots showing time to first severe exacerbation in the 21 days following first day with > 2, > 4, > 6 and > 8 reliever inhalations.

Tab. 1 Number of patients with a severe exacerbation in the 21 days following first day with > 2, > 4, > 6, and > 8 reliever inhalations.

As-needed terbutaline 0.5 mg (n = 1277)

As-needed BUD/FORM 200/6 µg (n = 1277)

BUD maintenance 200 µg bid + as-needed terbutaline (n = 1282)

*  Hazard ratios not calculated in view of low exacerbation rates in the as-needed BUD/FORM group.

> 2 “as-needed” inhalations

Patients with > 2 reliever inhalations on ≥ 1day, n (%)

936 (73.3)

850 (66.6)

758 (59.1)

Patients with severe exacerbations within 21 days, n (%)

37 (4.0)

10 (1.2)

11 (1.5)

Hazard ratio (95% CI)

Reference group

0.30 (0.15, 0.61) p = 0.001

0.37 (0.19, 0.73) p = 0.004

3.33 (1.65, 6.69) p = 0.001

Reference group

1.24 (0.53, 2.91) p = 0.63

> 4 “as-needed” inhalations

Patients with > 4 reliever inhalations on ≥ 1day, n (%)

526 (41.2)

303 (23.7)

311 (24.3)

Patients with severe exacerbations within 21 days, n (%)

40 (7.6)

5 (1.7)

9 (2.9)

Hazard ratio (95% CI)

Reference group

0.24 (0.09, 0.60) p = 0.002

0.41 (0.20, 0.84) p = 0.015

4.24 (1.67, 10.75) p = 0.002

Reference group

1.73 (0.58, 5.15) p = 0.328

> 6 “as-needed” inhalations

Patients with > 6 reliever inhalations on ≥ 1day, n (%)

281 (22.0)

102 (8.0)

142 (11.1)

Patients with severe exacerbations within 21 days, n (%)

22 (7.8)

1 (1.0)

6 (4.2)

Hazard ratio (95% CI)

Reference group

–

0.61 (0.25, 1.51) p = 0.287

> 8 “as-needed” inhalations*

Patients with > 8 reliever inhalations on ≥ 1day, n (%)

170 (13.3)

49 (3.8)

67 (5.2)

Patients with severe exacerbations within 21 days, n (%)

15 (8.8)

0 (0.0)

2 (3.0)

Conclusions In mild asthma, anti-inflammatory reliever therapy with BUD/FORM as-needed reduces higher reliever use days and reduces exacerbations within the next 21 days vs. terbutaline as-needed.