What do systematic reviews say?

Combination of anticholinergics + beta2‐agonists vs B2‐agonists alone

• Inhaled anticholinergics and short‐acting beta₂‐agonists versus short‐acting beta2‐agonists alone for children with… 2014 · Cochrane Headline outcomes only
  no estimate extracted
  2 studies · 290 participants
  Moderate

LABA/LAMA vs LABA plus inhaled corticosteroid (ICS)

Long‐acting muscarinic antagonist (LAMA) plus long‐acting… showed no clear difference in serious adverse events (number of people experiencing ≥ 1 SAEs) compared with LABA plus inhaled corticosteroid (ICS) (high certainty).

• Long‐acting muscarinic antagonist (LAMA) plus long‐acting beta‐agonist (LABA) versus LABA plus inhaled corticosteroid… 2023 · Cochrane Headline outcomes only
  OR 1.02 [0.91, 1.15]
  18 studies · 23183 participants
  High

LAMA add‐on vs long‐acting beta2‐agonists (LABA) add‐on

Long‐acting muscarinic antagonists (LAMA) add‐on showed no clear difference in adverse events (all) compared with long‐acting beta2‐agonists (LABA) add‐on (moderate certainty).

• Long‐acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus addition of long‐acting… 2015 · Cochrane Headline outcomes only
  OR 1.11 [0.92, 1.35]
  3 studies · 1839 participants
  Moderate

LAMA add‐on vs long‐acting beta2‐agonists (LABA) add‐on

Long‐acting muscarinic antagonists (LAMA) add‐on showed no clear difference in serious adverse events 22 weeks compared with long‐acting beta2‐agonists (LABA) add‐on (low certainty).

• Long‐acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus addition of long‐acting… 2015 · Cochrane Headline outcomes only
  OR 0.84 [0.41, 1.73]
  4 studies · 2012 participants
  Low

Combination inhaled therapy vs SABA

Combination inhaled therapy probably leads to higher total adverse events compared with SABA alone (moderate certainty).

• Combined inhaled beta‐agonist and anticholinergic agents for emergency management in adults with asthma 2017 · Cochrane Headline outcomes only
  OR 2.03 [1.28, 3.2]
  11 studies · 1392 participants
  Moderate

As‐required FABA/ICS inhalers vs regular inhaled steroid

As‐required FABA/ICS inhalers showed no clear difference in adverse events compared with regular inhaled steroid (moderate certainty).

• Combination fixed‐dose beta agonist and steroid inhaler as required for adults or children with mild asthma 2021 · Cochrane Headline outcomes only
  OR 0.96 [0.82, 1.14]
  4 studies · 8072 participants
  Moderate

Stopping LABA vs continuing use of LABA+ICS

Stopping LABA showed no clear difference in adverse events (all) compared with continuing use of LABA+ICS (moderate certainty).

• Stopping long‐acting beta₂‐agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids 2015 · Cochrane Headline outcomes only
  OR 0.83 [0.66, 1.05]
  5 studies · 1339 participants
  Moderate

Intervention not reported

The intervention showed no clear difference in serious adverse events (moderate certainty).

• Addition of long‐acting beta₂‐agonists to inhaled corticosteroids for chronic asthma in children 2015 · Cochrane Headline outcomes only
  RR 1.54 [0.81, 2.94]
  7 studies · 1343 participants
  Moderate

Intervention not reported

The intervention showed no clear difference in serious adverse events (moderate certainty).

• Addition of long‐acting beta₂‐agonists to inhaled corticosteroids for chronic asthma in children 2015 · Cochrane Headline outcomes only
  RR 1.17 [0.75, 1.85]
  16 studies · 4022 participants
  Moderate

LABA/ICS vs LTRA + ICS

LABA + ICS showed no clear difference in serious adverse events compared with LTRA + ICS (moderate certainty).

• Addition to inhaled corticosteroids of long‐acting beta₂‐agonists versus anti‐leukotrienes for chronic asthma 2014 · Cochrane Headline outcomes only
  RR 1.33 [0.99, 1.79]
  9 studies · 6288 participants
  Moderate

Intervention not reported

The intervention leads to lower any adverse events 49 weeks (high certainty).

• Long‐acting muscarinic antagonists (LAMA) added to combination long‐acting beta₂‐agonists and inhaled corticosteroids… 2016 · Cochrane Headline outcomes only
  OR 0.7 [0.52, 0.94]
  3 studies · 1197 participants
  High

Intervention not reported

The intervention showed no clear difference in total number of adverse events (high certainty).

• Addition of long‐acting beta₂‐agonists to inhaled corticosteroids for chronic asthma in children 2015 · Cochrane Headline outcomes only
  RR 1.01 [0.92, 1.1]
  6 studies · 1254 participants
  High

Intervention not reported

The intervention showed no clear difference in total number of adverse events (moderate certainty).

• Addition of long‐acting beta₂‐agonists to inhaled corticosteroids for chronic asthma in children 2015 · Cochrane Headline outcomes only
  RR 1.04 [0.98, 1.1]
  15 studies · 3284 participants
  Moderate

Intervention not reported

The intervention showed no clear difference in serious adverse events 49 weeks (low certainty).

• Long‐acting muscarinic antagonists (LAMA) added to combination long‐acting beta₂‐agonists and inhaled corticosteroids… 2016 · Cochrane Headline outcomes only
  OR 0.6 [0.24, 1.47]
  3 studies · 1197 participants
  Low

Stopping LABA vs continuing use of LABA+ICS

Stopping LABA showed no clear difference in serious adverse events 17 weeks compared with continuing use of LABA+ICS (moderate certainty).

• Stopping long‐acting beta₂‐agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids 2015 · Cochrane Headline outcomes only
  OR 0.82 [0.28, 2.42]
  5 studies · 1342 participants
  Moderate

Tiotropium + LABA/ICS combination vs tiotropium

Tiotropium + LABA/ICS combination showed no clear difference in serious adverse events (non‐fatal) compared with tiotropium (low certainty).

• Combination inhaled steroid and long‐acting beta₂‐agonist in addition to tiotropium versus tiotropium or combination… 2016 · Cochrane Headline outcomes only
  OR 0.86 [0.57, 1.3]
  4 studies · 1758 participants
  Low

Intervention not reported

The intervention showed no clear difference in adverse events－serious Mometasone/formoterol (MF/F) versus… (low certainty).

• Combined corticosteroid and long‐acting beta₂‐agonist in one inhaler versus inhaled corticosteroids alone for chronic… 2013 · Cochrane Headline outcomes only
  OR 1.03 [0.63, 1.67]
  2 studies · 905 participants
  Low

Intervention not reported

The intervention showed no clear difference in adverse events－serious Fluticasone/salmeterol (FPS) versus… (low certainty).

• Combined corticosteroid and long‐acting beta₂‐agonist in one inhaler versus inhaled corticosteroids alone for chronic… 2013 · Cochrane Headline outcomes only
  OR 1.05 [0.82, 1.34]
  7 studies · 5055 participants
  Low

Intervention not reported

It is very uncertain whether the intervention changes adverse events－serious events Budesonide/formoterol (BDF) versus… (very low certainty).

• Combined corticosteroid and long‐acting beta₂‐agonist in one inhaler versus inhaled corticosteroids alone for chronic… 2013 · Cochrane Headline outcomes only
  OR 0.93 [0.72, 1.21]
  3 studies · 1469 participants
  Very low