1 # patients with exacerbations requiring systemic steroids Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

1.1 Mean baseline FEV 1 >/= 80% of predicted

7

1510

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.56, 0.86]

1.2 Mean baseline FEV1 61‐79% of predicted

9

2186

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.72, 0.97]

1.3 Mean baseline FEV 1 not reported

1

331

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.79, 1.07]

2 # patients with exacerbations requiring hospitalisation Show forest plot

11

4162

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.50, 1.33]

2.1 Mean baseline FEV 1 >/= 80% of predicted

2

139

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.18, 5.39]

2.2 Mean baseline FEV 1 61‐79% of predicted

7

2781

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.58, 1.96]

2.3 Mean baseline FEV 1 not reported

2

1242

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.14, 1.08]

3 FEV1 (L) at endpoint Show forest plot

6

914

Mean Difference (IV, Fixed, 95% CI)

0.15 [0.07, 0.22]

3.1 Mean Baseline FEV1 >/‐80% of predicted

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Mean baseline FEV 1 61‐79% of predicted

6

914

Mean Difference (IV, Fixed, 95% CI)

0.15 [0.07, 0.22]

4 Change in FEV1 at endpoint (L) stratifying on baseline FEV1 Show forest plot

9

1847

Mean Difference (IV, Random, 95% CI)

0.17 [0.11, 0.24]

4.1 Mean baseline FEV1 >=80% of predicted

1

21

Mean Difference (IV, Random, 95% CI)

0.42 [0.21, 0.63]

4.2 Mean baseline FEV1 61‐79% of predicted

8

1826

Mean Difference (IV, Random, 95% CI)

0.16 [0.10, 0.22]

5 Change in FEV1 at endpoint (% predicted) stratifying on baseline FEV1 Show forest plot

4

1428

Mean Difference (IV, Fixed, 95% CI)

2.79 [1.89, 3.69]

5.1 Mean baseline FEV1 >/= 80 % predicted

4

1428

Mean Difference (IV, Fixed, 95% CI)

2.79 [1.89, 3.69]

6 FEV1 % predicted at endpoint Show forest plot

3

881

Mean Difference (IV, Fixed, 95% CI)

5.93 [3.74, 8.11]

6.1 Mean Baseline FEV1 >‐80% of predicted

1

29

Mean Difference (IV, Fixed, 95% CI)

6.25 [‐2.58, 15.08]

6.2 Mean Baseline FEV1 61‐79% of predicted

2

852

Mean Difference (IV, Fixed, 95% CI)

5.90 [3.65, 8.16]

7 Change in FEV1 (L or % pred )stratifying on trial duration Show forest plot

13

3926

Std. Mean Difference (IV, Random, 95% CI)

0.35 [0.28, 0.42]

7.1 Change in FEV1 (L) or (% predicted) at 6 +/‐ 2 weeks of treatment

2

299

Std. Mean Difference (IV, Random, 95% CI)

0.41 [0.18, 0.64]

7.2 Change in FEV1 (L) or (% predicted) at 12 +/‐ 4 weeks of treatment

11

2003

Std. Mean Difference (IV, Random, 95% CI)

0.36 [0.24, 0.49]

7.3 Change in FEV1 (L) or (% predicted) at 24 +/‐ 4 weeks of treatment

2

352

Std. Mean Difference (IV, Random, 95% CI)

0.30 [0.09, 0.51]

7.4 Change in FEV1 (L) or (% predicted) at 52 +/‐ 4 weeks of treatment

2

1272

Std. Mean Difference (IV, Random, 95% CI)

0.32 [0.21, 0.43]

8 Morning PEF (L/min) at endpoint Show forest plot

6

1156

Mean Difference (IV, Random, 95% CI)

22.62 [4.34, 40.90]

8.1 Mean baseline FEV1 >/= 80%

1

29

Mean Difference (IV, Random, 95% CI)

86.0 [17.11, 154.89]

8.4 Mean baseline FEV1 61‐79% of predicted

5

1127

Mean Difference (IV, Random, 95% CI)

19.14 [2.93, 35.34]

9 Change in morning PEF (L/min) at endpoint stratifying on baseline FEV1 Show forest plot

17

4885

Mean Difference (IV, Random, 95% CI)

23.28 [18.38, 28.18]

9.1 Mean Baseline FEV1 >/= 80% of predicted

4

1410

Mean Difference (IV, Random, 95% CI)

14.76 [7.47, 22.04]

9.2 Mean Baseline FEV1 61‐79% of predicted

12

3144

Mean Difference (IV, Random, 95% CI)

25.46 [19.47, 31.44]

9.4 Mean Baseline FEV1 not reported

1

331

Mean Difference (IV, Random, 95% CI)

24.30 [15.04, 33.56]

10 Evening PEF (L/min) at endpoint Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

10.1 Mean baseline FEV1 61‐79% of predicted

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 Change in evening PEF (L/min) at endpoint Show forest plot

9

2230

Mean Difference (IV, Random, 95% CI)

21.33 [14.53, 28.12]

11.1 Mean baseline FEV1 61‐79% of predicted

8

2209

Mean Difference (IV, Random, 95% CI)

19.93 [14.09, 25.77]

11.2 Mean baseline FEV1 > /= 80% of predicted

1

21

Mean Difference (IV, Random, 95% CI)

90.0 [39.82, 140.18]

12 Change in PEF variability at endpoint Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

12.3 Mean baseline FEV 1 61‐79% of predicted

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13 Change in daytime symptom score at endpoint Show forest plot

5

1371

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.34 [‐0.44, ‐0.23]

13.3 Mean baseline FEV1 61‐79% of predicted

5

1371

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.34 [‐0.44, ‐0.23]

14 Change in nightime symptom score at endpoint Show forest plot

2

922

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.31, ‐0.05]

14.1 Mean baseline FEV 1 61‐79% of predicted

2

922

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.31, ‐0.05]

15 Change in 24 hour symptom score at endpoint Show forest plot

2

362

Mean Difference (IV, Fixed, 95% CI)

‐0.28 [‐0.45, ‐0.11]

15.1 Mean baseline FEV 1 61‐79% of predicted

2

362

Mean Difference (IV, Fixed, 95% CI)

‐0.28 [‐0.45, ‐0.11]

16 % symptom‐free days Show forest plot

4

1678

Std. Mean Difference (IV, Random, 95% CI)

0.32 [0.02, 0.62]

16.1 Mean baseline FEV1 61‐79% of predicted

3

1051

Std. Mean Difference (IV, Random, 95% CI)

0.37 [‐0.04, 0.78]

16.2 Mean baseline FEV1 >/=80% of predicted

1

627

Std. Mean Difference (IV, Random, 95% CI)

0.18 [0.03, 0.34]

17 Change in % symptom‐free days at endpoint Show forest plot

6

1317

Mean Difference (IV, Random, 95% CI)

17.21 [12.06, 22.36]

17.1 Mean baseline FEV 1 >/=80% of predicted

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Mean baseline FEV 1 61‐79% of predicted

6

1317

Mean Difference (IV, Random, 95% CI)

17.21 [12.06, 22.36]

18 % symptom‐free nights at 12 +/‐ 4 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

18.1 Mean baseline FEV 1 61‐79% of predicted

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

19 Change in % symptom‐free nights at endpoint Show forest plot

4

1052

Std. Mean Difference (IV, Random, 95% CI)

0.51 [0.28, 0.74]

19.1 Mean baseline FEV 1 61‐79% of predicted

4

1052

Std. Mean Difference (IV, Random, 95% CI)

0.51 [0.28, 0.74]

20 Change in Asthma Control days % @ 12 +/‐ 4 weeks Show forest plot

2

362

Mean Difference (IV, Fixed, 95% CI)

15.61 [8.51, 22.70]

20.1 Mean baseline FEV 1 61‐79% of predicted

2

362

Mean Difference (IV, Fixed, 95% CI)

15.61 [8.51, 22.70]

21 # daytime rescue inhalations (puffs per day) at endpoint Show forest plot

2

277

Mean Difference (IV, Random, 95% CI)

‐0.73 [‐1.24, ‐0.22]

21.1 Mean baseline FEV 1 61‐79% of predicted

2

277

Mean Difference (IV, Random, 95% CI)

‐0.73 [‐1.24, ‐0.22]

22 Change in # daytime rescue inhalations (puffs per day) at endpoint Show forest plot

9

3003

Mean Difference (IV, Random, 95% CI)

‐0.82 [‐1.17, ‐0.47]

22.1 Mean baseline FEV 1 61‐79% of predicted

9

3003

Mean Difference (IV, Random, 95% CI)

‐0.82 [‐1.17, ‐0.47]

23 # nighttime rescue inhalations (puffs per night) at endpoint Show forest plot

2

546

Mean Difference (IV, Random, 95% CI)

‐0.44 [‐0.81, ‐0.07]

23.1 Mean baseline FEV 1 61‐79% of predicted

2

546

Mean Difference (IV, Random, 95% CI)

‐0.44 [‐0.81, ‐0.07]

24 Change in # nighttime rescue inhalations at endpoint Show forest plot

6

2051

Mean Difference (IV, Random, 95% CI)

‐0.33 [‐0.57, ‐0.10]

24.3 Mean baseline FEV1 61‐79% of predicted

6

2051

Mean Difference (IV, Random, 95% CI)

‐0.33 [‐0.57, ‐0.10]

25 Change in # overall daily rescue inhalations at endpoint Show forest plot

8

2745

Mean Difference (IV, Random, 95% CI)

‐0.81 [‐1.17, ‐0.44]

25.1 Mean baseline FEV 1 >/=80% of predicted

2

1272

Mean Difference (IV, Random, 95% CI)

‐0.17 [‐0.29, ‐0.05]

25.2 Mean baseline FEV 1 61‐79% of predicted

6

1473

Mean Difference (IV, Random, 95% CI)

‐1.29 [‐2.20, ‐0.38]

26 Change in mean % rescue free days at 12 +/‐ 4 weeks Show forest plot

2

362

Mean Difference (IV, Fixed, 95% CI)

19.1 [12.19, 26.01]

26.1 Mean baseline FEV 1 61‐79% of predicted

2

362

Mean Difference (IV, Fixed, 95% CI)

19.1 [12.19, 26.01]

27 Change in % nights with no awakening at 12 +/‐ 4 weeks Show forest plot

2

334

Mean Difference (IV, Fixed, 95% CI)

3.24 [‐0.89, 7.38]

27.1 Mean baseline FEV 1 61‐79% of predicted

2

334

Mean Difference (IV, Fixed, 95% CI)

3.24 [‐0.89, 7.38]

28 % nights with awakening Show forest plot

2

913

Mean Difference (IV, Fixed, 95% CI)

‐1.37 [‐2.75, 0.02]

28.1 Mean Baseline FEV1 >/= 80% of predicted

1

627

Mean Difference (IV, Fixed, 95% CI)

‐1.50 [‐3.19, 0.19]

28.2 Mean baseline FEV 1 61‐79% of predicted

1

286

Mean Difference (IV, Fixed, 95% CI)

‐1.10 [‐3.51, 1.31]

29 Change in night time awakening ( number of nights) at endpoint Show forest plot

3

648

Mean Difference (IV, Fixed, 95% CI)

‐0.22 [‐2.24, 1.81]

29.1 Mean baseline FEV 1 61‐79% of predicted

3

648

Mean Difference (IV, Fixed, 95% CI)

‐0.22 [‐2.24, 1.81]

30 Change in quality of life (AQLQ score) at endpoint Show forest plot

2

1169

Mean Difference (IV, Random, 95% CI)

0.33 [0.05, 0.60]

30.1 Mean baseline FEV 1 61‐79% of predicted

2

1169

Mean Difference (IV, Random, 95% CI)

0.33 [0.05, 0.60]

31 Total # withdrawals Show forest plot

26

6571

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.77, 0.97]

31.1 Mean baseline FEV1 >/=80% of predicted

5

248

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.22, 1.30]

31.2 Mean baseline FEV 1 61‐79% of predicted

19

5081

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.75, 0.99]

31.4 Mean baseline FEV1 not reported

2

1242

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.72, 1.13]

32 # withdrawals due to poor asthma control or exacerbation Show forest plot

23

5409

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.36, 0.70]

32.1 Mean baseline FEV 1 >/=80% of predicted

4

205

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.20, 3.40]

32.2 Mean baseline FEV 1 61‐79% of predicted

18

4293

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.37, 0.73]

32.3 Mean baseline FEV 1 not reported

1

911

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.08, 0.97]

33 # withdrawals due to adverse events Show forest plot

22

5892

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.96, 1.75]

33.1 Mean baseline FEV 1 >/=80% of predicted

3

175

Risk Ratio (M‐H, Fixed, 95% CI)

4.67 [0.23, 95.24]

33.2 Mean baseline FEV 1 61‐79% of predicted

18

4475

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.85, 1.79]

33.3 Mean baseline FEV 1 not reported

2

1242

Risk Ratio (M‐H, Fixed, 95% CI)

1.34 [0.79, 2.27]

34 # withdrawals due to serious non‐respiratory event Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

34.1 Mean baseline FEV 1 61‐79% of predicted

2

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

35 Total # adverse events Show forest plot

12

2393

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.92, 1.05]

35.1 Mean baseline FEV 1 >/=80% of predicted

2

140

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [1.00, 1.20]

35.2 Mean baseline FEV 1 61‐79% of predicted

10

2253

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.90, 1.05]

36 Serious adverse event including respiratory Show forest plot

4

886

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.30, 4.42]

36.1 Mean baseline FEV 1 61‐79% of predicted

4

886

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.30, 4.42]

37 # patients with headache Show forest plot

14

3221

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.92, 1.41]

37.1 Mean baseline FEV 1 >/=80%% of predicted

1

117

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.67, 1.60]

37.2 Mean baseline FEV 1 61‐79% of predicted

13

3104

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.91, 1.48]

38 # patients with hoarseness Show forest plot

3

544

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.16, 3.18]

38.1 Mean baseline FEV 1 61‐79% of predicted

3

544

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.16, 3.18]

39 # patients with oral thrush Show forest plot

6

828

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.35, 3.06]

39.1 Mean baseline FEV 1 61‐79% of predicted

4

675

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.35, 3.06]

39.2 FEV1 >/=80% predicted

2

153

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

40 # patients with tremor Show forest plot

10

2419

Risk Ratio (M‐H, Random, 95% CI)

2.48 [0.78, 7.89]

40.1 Mean baseline FEV 1 >/=80% of predicted

1

116

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

40.2 Mean baseline FEV 1 61‐79% of predicted

9

2303

Risk Ratio (M‐H, Random, 95% CI)

2.48 [0.78, 7.89]

41 # patients with tachycardia or palpitations Show forest plot

11

2580

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [0.77, 5.88]

41.1 Mean baseline FEV 1 >/=80% of predicted

1

116

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

41.2 Mean baseline FEV 1 61‐79% of predicted

10

2464

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [0.77, 5.88]

42 # patients with adverse cardiovascular events Show forest plot

4

792

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.32, 2.54]

42.1 Mean baseline FEV 1 >/=80% of predicted

1

116

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.01, 7.49]

42.2 Mean baseline FEV 1 61‐79% of predicted

3

676

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.35, 3.24]

43 Change in height (cm) as SD scores at 24 +/‐ 4 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

43.1 Mean baseline FEV 1 >/=80% of predicted

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

44 PC20 Methacholine‐adjusted odds ratio increase from baseline Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

44.1 Mean baseline FEV 1 61‐79% of predicted

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

45 ACTH induced cortisol <18microg/dl at endpoint Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

45.1 Mean baseline FEV 1 61‐79% of predicted

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

46 Am cortisol < 5 microg/dl at endpoint Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

46.1 Mean baseline FEV 1 61‐79% of predicted

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

47 Deaths Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

47.1 Mean baseline FEV 1 not reported

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

48 Change in # of symptom‐free nights at endpoint Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

48.1 Mean baseline FEV 1 61‐79% of predicted

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

49 # Worsening asthma Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

49.1 Mean baseline FEV 1 61‐79% of predicted

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

50 Change in % PC 20 at endpoint Show forest plot

1

39

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.68, 1.28]

50.1 Mean baseline FEV1 >/=80% of predicted

1

39

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.68, 1.28]

1 # patients with exacerbations requiring oral steroids by FEV1 % predicted at baseline Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

1.1 Mean baseline FEV 1 >/= 80% of predicted

7

1510

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.56, 0.86]

1.2 Mean baseline FEV1 61‐79% of predicted

9

2186

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.72, 0.97]

1.3 Mean baseline FEV 1 not reported

1

331

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.79, 1.07]

2 # patients with exacerbations requiring oral steroids children versus adults Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

2.1 Children

5

402

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.57, 1.42]

2.2 Adults

12

3625

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.73, 0.89]

3 # patients with exacerbations requiring oral steroids by dose of ICS in both groups Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

3.1 Low dose of ICS (<= 400 mcg/day of BDP‐eq)

6

1881

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.60, 0.84]

3.2 Moderate dose of ICS (401‐800 mcg/day of BDP‐eq)

5

1050

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.72, 0.97]

3.3 High dose of ICS (>800 mcg/day of BDP‐eq)

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.47 [0.83, 2.61]

3.4 Unspecified dose of ICS or range of dose only mentioned

5

977

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.71, 1.17]

4 # patients with exacerbations requiring oral steroids by combination inhaler or separate inhaler for LABA Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

4.1 Combination inhaler

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

2.46 [0.25, 24.21]

4.2 Separate inhaler

15

3961

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

4.3 Not reported

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.03, 1.64]

5 # patients with exacerbations requiring oral steroids by whether LABA dose is usual or higher than usual Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

5.2 LABA at usual dose

14

3646

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.70, 0.87]

5.3 LABA at higher than usual dose

3

381

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.79, 1.52]

6 # patients with exacerbations requiring oral steroids by type of LABA Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

6.1 Formoterol

7

2575

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.63, 0.84]

6.2 Salmeterol

10

1452

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.81, 1.07]

7 # patients with exacerbations requiring oral steroids by trial duration Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

7.1 <12 weeks

4

147

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.22, 1.83]

7.2 <24 >/= 12 weeks

5

889

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.75, 1.24]

7.3 >=24 weeks

8

2991

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.70, 0.87]

8 # patients with exacerbations requiring oral steroids study unsupported by pharmaceutical industry excluded Show forest plot

17

4027

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

8.1 Charity Funded

1

23

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.28, 4.32]

8.2 Funded by pharmaceutical industry

16

4004

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

9 # patients with exacerbations requiring oral steroids with studies with Jadad score < 4 excluded Show forest plot

14

3855

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

9.1 Jadad score < 4

2

69

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.03, 1.64]

9.2 Jadad score > 4

12

3786

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.73, 0.90]

10 Change in FEV1 at endpoint (L or % predicted) stratifying by adult or pediatric study Show forest plot

13

3275

Std. Mean Difference (IV, Random, 95% CI)

0.37 [0.26, 0.48]

10.1 Pediatric

4

340

Std. Mean Difference (IV, Random, 95% CI)

0.56 [‐0.06, 1.18]

10.2 Adult

9

2935

Std. Mean Difference (IV, Random, 95% CI)

0.37 [0.26, 0.48]

11 Change in FEV1 at endpoint (L or % predicted) stratifying by type of LABA used. Show forest plot

13

3275

Std. Mean Difference (IV, Random, 95% CI)

0.37 [0.26, 0.48]

11.1 Formoterol

5

1999

Std. Mean Difference (IV, Random, 95% CI)

0.30 [0.21, 0.38]

11.2 Salmeterol

8

1276

Std. Mean Difference (IV, Random, 95% CI)

0.47 [0.27, 0.68]