Prospective data on exacerbations and exacerbation-related outcomes in mild asthma from placebo arms of RCTs of ≥24 weeks' duration

Study (year) [ref.]Age range yearsPlacebo nOther asthma medication in placebo armTreatment durationExacerbation parameterPlacebo arm
Studies not excluding patients with exacerbation history+
 Bisgaard et al. (2005) [27]2–5271Rescue OCS or ICS or β2-agonist48 wksPts with exacerbation§56%
Exacerbation rate/year (n=257)ƒ2.34
Median time to first exacerbation147 days
Pts with ≥1 unscheduled visit to physician for asthmaƒ42.4%
Pts hospitalised for asthmaƒ5.8%
Rate of OCS courses/yearƒ0.64
 Chuchalin et al. (2008) [32]12–79315Rescue ALB52 wksMean exacerbation rate per pt per year (mild, moderate, severe)2.88
Moderate (OCS) or severe exacerbation (hospitalisation) rate/year0.33
No. unscheduled asthma-related healthcare contacts7
Pt withdrawal/discontinued due to exacerbation, n8
 Martinez et al. (2011) [36]5–1874Rescue ALB44 wksProbability (95% CI) of first exacerbation by end of trial requiring prednisone course49 (37–61)%
Proportion with treatment failure (all defined by requirement for a second course of prednisone)23%
 O'Byrne et al. (2001) [39]≥12239Yes - only after first exacerbation (n=104)¶¶1 yrPts with severe exacerbation33.3%
No. of pts with severe exacerbation, pts treated with OCSs70.9%
Pts receiving systemic corticosteroids23.6%
Severe exacerbation rate per pt per year0.77
 O’Byrne et al. (2018) [38]≥121277TERB 0.5 mg as needed1 yrPts with ≥1 moderate or severe exacerbation21.5%
Pts with ≥1 severe exacerbation11.9%
Annualised severe exacerbation rate0.20
 Papi et al. (2007) [40]18–65118ALB as-needed6 monthsPts with severe exacerbation3.4%
Pts with ≥1 exacerbation17.80%
Mean no. of exacerbations/pt/year1.63
 Pauwels et al. (2003) [41]5–663568Usual asthma treatment (SABA 64.6% of placebo pts) plus ICS or systemic corticosteroid if needed3 yrsPts with life-threatening exacerbation over 3 years, n24 (0.67%)
Pts with ≥1 SARE over 3 years, n198
Pts with ≥2 SAREs over 3 years, n49
Mean no. of courses of systemic corticosteroids per year0.21
Pts using systemic corticosteroids3 months: 4.1%
12 months: 3.1%
24 months: 3.3%
36 months: 2.0%
Pts with ≥1 systemic corticosteroid course23%
Studies excluding patients with exacerbation history+
 Reddel et al. (2008) [42]18–8021ALB as-needed11 monthsPts with ≥1 mild exacerbation, n13
Pts with severe exacerbation, n3
Studies requiring patients to have a history of frequent exacerbations#
 Robertson et al. (2007) [21]2–14113Inhaled β2-agonist or OCS for acute asthma episode12 monthsProportion of children with ≥1 episode treated with short course of randomised therapy, n (%)105 (92.9%)
Total number of treated episodes of asthma336
Proportion of treated asthma episodes utilising ≥1 health resource, n (%)134 (39.9%)
Proportion of treated asthma episodes requiring ED visit, n (%)46 (13.7%)
Proportion of treated asthma episodes requiring hospitalisation, n (%)13 (3.9%)
Proportion of treated asthma episodes with OCS use, n/N pts with diary data (%)78 of 321 (24.3%)

RCT: randomised controlled trial; ED: emergency department; wks: weeks; pt: patient; OCS: oral corticosteroid; ICS: inhaled corticosteroid; CI: confidence interval; SABA: short-acting β2-agonist; SARE: severe asthma-related event; ALB: albuterol; TERB: terbutaline; GP: general practitioner; LABA: long-acting β2-agonist. # Study included only patients with a history of 3–6 exacerbations (hospitalisation or ED visit or GP visits) within 12 months prior to enrolment/screening); Unscheduled visits to GP, specialist paediatrician, ED or admission to hospital; +: Exacerbation history defined as an exacerbation, hospitalisation or ED visit or OCS use occurring ≥3 months prior to enrolment/screening; §: data appear to relate to 48-week double-blind period only (total study duration 1 year including screening and single-blind, placebo run-in period); ƒ: source publication refers to “yearly” data, but double-blind treatment period only 48 weeks (total study duration 1 year including screening and single-blind, placebo run-in period); ##: defined as the requirement for a second dose of prednisone within any 6-month period; ¶¶: most common extra medication in placebo group was systemic corticosteroids (n=56), ICS (n=15) and LABAs (n=11).