Vilanterol and fluticasone furoate for asthma

Kerry Dwan; Stephen J Milan; Lynne Bax; Nicola Walters; Colin VE Powell

doi:10.1002/14651858.CD010758.pub2

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 FF/VI 100/25 versus placebo, Outcome 1 Change in quality of life (measured by AQLQ at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 FF/VI 100/25 versus placebo, Outcome 2 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 FF/VI 100/25 versus placebo, Outcome 3 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 FF/VI 100/25 versus placebo, Outcome 4 FEV1 Litres.

Analysis 1.4

Comparison 1 FF/VI 100/25 versus placebo, Outcome 4 FEV₁ Litres.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 FF/VI 100/25 versus placebo, Outcome 5 PEFR AM L/min (change from baseline at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 FF/VI 100/25 versus placebo, Outcome 6 PEFR PM L/min (change from baseline at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 FF/VI 100/25 versus placebo, Outcome 7 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 1 Change in quality of life (measured by AQLQ at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 2 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 3 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 4 Trough FEV1 (L).

Analysis 2.4

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 4 Trough FEV₁ (L).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 5 PEFR AM (change from baseline at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 6 PEFR PM (change from baseline at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.7

Comparison 2 FF/VI 100/25 versus same dose of FF, Outcome 7 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 FF/VI 100/25 versus same dose VI, Outcome 1 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 FF/VI 100/25 versus FP 500 µg, Outcome 1 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.2

Comparison 4 FF/VI 100/25 versus FP 500 µg, Outcome 2 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.1

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 1 Change in quality of life (measured by AQLQ at 24 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.2

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 2 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.3

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 3 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 4 FEV1.

Analysis 5.4

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 4 FEV₁.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.5

Comparison 5 FF/VI 100/25 versus FPS 250/50 bd, Outcome 5 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.1

Comparison 6 FF/VI 100/25 µg versus FF/VI 200/25 µg, Outcome 1 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.2

Comparison 6 FF/VI 100/25 µg versus FF/VI 200/25 µg, Outcome 2 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.1

Comparison 7 FF/VI 200/25 versus placebo, Outcome 1 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.2

Comparison 7 FF/VI 200/25 versus placebo, Outcome 2 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 FF/VI 200/25 versus placebo, Outcome 3 FEV1 Litres.

Analysis 7.3

Comparison 7 FF/VI 200/25 versus placebo, Outcome 3 FEV₁ Litres.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.4

Comparison 7 FF/VI 200/25 versus placebo, Outcome 4 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.1

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 1 Change in quality of life (measured by AQLQ at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.2

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 2 Change in quality of life (measured by AQLQ at 24 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.3

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 3 OLD***Health‐related quality of life.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.4

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 4 Exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.5

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 5 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.6

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 6 PEFR.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.7

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 7 PEFR AM.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.8

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 8 PEFR PM.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.9

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 9 % symptom‐free days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.10

Comparison 8 FF/VI 200/25 µg versus FP 500 µg, Outcome 10 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.1

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 1 Change in quality of life (measured by AQLQ at 12 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.2

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 2 Change in quality of life (measured by AQLQ at 24 wk).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.3

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 3 Serious adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 4 FEV1 Litres.

Analysis 9.4

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 4 FEV₁ Litres.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.5

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 5 PEFR AM.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.6

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 6 PEFR PM.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.7

Comparison 9 FF/VI 200/25 versus same dose of FF, Outcome 7 Change in asthma symptoms (measured by ACT).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Vilanterol and fluticasone furoate compared with placebo for asthma

VI and FF compared with placebo for asthma
Patient or population: people with asthma Settings: community Intervention: VI and FF Comparison: placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	Placebo	VI and FF
Health‐related quality of life	0.61 (SE 0.061), n = 149	0.91 (SE 0.055), n = 180	MD 0.30, 95% CI 0.14 to 0.46	Bleecker 2012 (N = 609 participants, 515 completed study) compared VI/FF 100/25 mcg vs placebo in respect of health‐related quality of life and indicated a significant advantage for VI/FF 100/25 mcg	Moderate^a
Asthma exacerbation			Not estimable	Only 2 studies (Allen 2013 and Kempsford 2012a) compared VI/FF 100/25 mcg vs placebo in respect of exacerbations; both studies reported no exacerbations in either treatment arm	Very low^b
Serious adverse events			Not estimable	Five trials (Allen 2013; Bleecker 2012; Kempsford 2012a; Oliver 2012; Oliver 2013) made this same comparison in relation to serious adverse events; all 5 reported no serious adverse events in VI/FF100/25 mcg or placebo arms	Very low^b
FEV₁	0.196 L (SE 0.0310), n = 193	0.368 L (SE 0.0304), n = 200	MD 0.17 L, 95% CI 0.09 to 0.26	Significant difference in favour of VI/FF 100/25 mcg vs placebo with respect to mean change in trough FEV₁ (pre‐bronchodilator and pre‐dose) from baseline to week 12 in 1 trial (Bleecker 2012) (N = 609 participants, 515 completed study) (MD 0.17 L, 95% CI 0.09 to 0.26), and a similar effect was found in a small cross‐over trial (Kempsford 2012a) over a 2‐week period in the morning (MD 0.377 L, 90% CI 0.293 to 0.462) and in the evening (MD 0.422 L, 90% CI 0.337 to 0.507)	Moderate^c
Peak expiratory flow	‐0.4 L/min (SE 2.42), n = 203	32.9 L/min (SE 2.42), n = 201	MD 33.30 L/min, 95% CI 26.59 to 40.01	Bleecker 2012 (N = 609 participants, 515 completed study) compared VI/FF 100/25 mcg vs placebo as mean change from baseline in daily morning (AM) PEF averaged over 12‐week treatment period; researchers noted a significant difference in favour of VI/FF 100/25 mcg (MD 33.30 L/min, 95% CI 26.59 to 40.01). The same trial showed a similar advantage in favour of VI/FF 100/25 mcg vs placebo in the evening over this period (28.20 L/min, 95% CI 21.67 to 34.73). A small cross‐over trial (Kempsford 2012a) produced a similar effect in favour of VI/FF 100/25 mcg vs placebo over a 2‐week period in the morning (MD 44.0 L/min, 90% CI 31.2 to 56.9) and in the evening (MD 69.0 L/min, 90% CI 55.9 to 82.1)	Moderate^c
Asthma symptoms	14.6 (SE 2.15), n = 202	32.5 (SE 2.14), n = 201	MD 17.90, 95% CI 11.95 to 23.85	Only 1 trial (Bleecker 2012) (N = 609 participants, 515 completed study) made VI/FF vs placebo comparison with respect to asthma symptoms, indicating a clear advantage for VI/FF 100/25 mcg	Moderate^a
Adverse events			Not estimable	Several trials reported a range of adverse events for which overall aggregation was not possible. These are tabulated in Table 8	Moderate^d
The basis for the assumed risk* (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) AM: morning; CI: confidence interval; FEV₁: forced expiratory volume in one second; FF: fluticasone furoate; GRADE: Grades of Recommendation, Assessment, Development and Evaluation Working Group; MD: mean difference; OR: odds ratio; PEF: peak expiratory flow; PM: afternoon; RR: risk ratio; SE: standard error; VI: vilanterol
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: We are very uncertain about the estimate
^aPoint deducted to reflect that these data were derived from only one trial ^bInvestigators reported no events in either arm of these trials ^cPoint deducted to reflect that data contributing to the main result (MD 0.17 L, 95% CI 0.09 to 0.26) were obtained from only one trial ^dPoint deducted, as we were unable to combine data on this outcome; results are presented in a separate table

Summary of findings for the main comparison. Vilanterol and fluticasone furoate compared with placebo for asthma

Ir a la tabla de la revisión

Table 8. Adverse events

Study	FF/VI 100/25 mcg	FF 100 mcg	FF 200 mcg	FF/VI 200/25 mcg	VI 25 mcg	FP/SAL 250/50 mcg twice‐daily	FP 500 mcg	Prednisolone 10 mg	Placebo
Allen 2013 6 weeks' duration. On‐treatment AEs	23/56 (41.00%)	‐	‐	21/56 (38.00%)	‐	‐	‐	5/15 (33.00%)	16/58 (28.00%)
Bateman 2014 ≥24 to 78 weeks' duration. On‐treatment AEs	636/1009 (63.00%)	652/1010 (65.00%)	‐	‐	‐	‐	‐	‐	‐
Bernstein 2014 12 weeks' duration	54/346 (15.61%)	67/347 (19.31%)	‐	52/346 (15.03%)	‐‐		‐	‐	‐
Bleecker 2012 12 weeks' duration	29/201 (14.43%)	20/205 (9.76%)	‐	‐	‐	‐	‐	‐	22/203 (10.84%)
Busse 2013 52 weeks' duration. On‐treatment AEs	139/201 (69.15%)	‐	‐	134/202 (66.34%)	‐	‐	73/100 (73.00%)	‐	‐
Lee 2014 Cross‐over trial. 3 of 7 treatments (2 weeks) separated by 12 to 14‐day washout periods	43/172 (25%)	25/187 (13%)	‐	‐	‐	‐	‐	‐	‐
Lin 2013 12 weeks' duration. Any AE	‐	‐	‐	40/155 (26.00%)	‐	‐	41/154 (27.00%)	‐	‐
Kempsford 2012 Cross‐over trial. Each period lasted 14 days with a 14 to 21‐day washout period between periods	11/24 (45.83%) AM 12/25 (48.00%) PM	‐	‐	‐	‐	‐	‐	‐	8/23 (34.78%)
NCT01134042 24 weeks' duration	‐	‐	66/194 (34.02%)	62/197 (31.47%)	‐	‐	73/195 (37.44%)	‐	‐
NCT01453023 Cross‐over trial. 11 weeks (for a single period)	4/25 (16.00%)	1/25 (4.00%)	‐	‐	‐	‐	‐	‐	‐
Oliver 2012 Cross‐over trial. 28 days for each period	11/51 (21.57%)	18/51 (35.29%)	‐	‐	‐	‐	‐	‐	15/51 (29.41%)
Oliver 2013 Cross‐over trial. 21 days	20/27 (74.07%)	19/27 (70.37%)	‐	‐	22/26 (84.62%)	‐	‐	‐	19/27 (70.37%)
Woodcock 2013 24 weeks' duration	110/403 (27.30%)	‐	‐	‐	‐	106/403 (26.30%)	‐	‐	‐
Fractions shown in the table indicate the proportions of people who suffered one or more adverse events of any cause in each treatment arm AE: adverse event; F: fluticasone furoate; FP: fluticasone propionate; SAL: salmeterol; VI: vilanterol

Table 8. Adverse events

Ir a la tabla de la revisión

Table 1. Summary of study characteristics

Study	Duration (weeks)	Severity at baseline	Inclusion criteria	Adverse events
Allen 2013	6	Reversibility > 12% FEV₁ > 50% of predicted	Adults Comply with treatment Clinical diagnosis of asthma for ≥ 12 weeks	Cortisol urinary excretion, serum AUC and trough
Bateman 2014	24 to 78	Reversibility > 12% FEV₁ > 50% to 90% of predicted	Adults Using ICS History of ≥ 1 exacerbation requiring hospitalisation or steroids in the past year	None
Bernstein 2014	12	Reversibility > 12% FEV₁ 50% to 80% of predicted	ICS for > 12 weeks before study > 12 years of age	Yes, not clear
Bleecker 2012	12	Pre‐bronchodilator FEV₁ 40% to 90% of predicted normal Reversibility FEV₁ ≥ 12%	ICS for 12 weeks before study > 12 years of age	Details not stated
Busse 2013	52	Pre‐bronchodilator FEV₁ 40% to 90% of predicted normal Reversibility FEV₁ ≥ 12%	Adults Clinical diagnosis of asthma ICS at high dose	Details not stated
Hojo 2015	4	ACT suggesting poor control and FEV₁ mean 70% (SD 11%)	Asthma ≥ 20 years of age	No, conference abstract only
Lee 2014	4	Pre‐bronchodilator FEV₁ 40% to 80% of predicted Demonstrated reversibility by ≥ 12%	Need for regular controller therapy for minimum of 8 weeks Stable dose of ICS for ≥ 4 weeks ≥ 18 years of age Diagnosis of asthma for ≥ 6 months	No
Lin 2013	12	Reversibility of disease: demonstrated ≥ 12% and FEV₁ 40% to 90%	ICS, with or without LABA, for ≥ 12 weeks Clinical diagnosis of asthma for 12 weeks Adults	No
Kempsford 2012	6 to 8	Pre‐bronchodilator FEV₁ ≥ 60% of predicted.	18 and 70 years of age inclusive Using an ICS, with or without a SABA, for ≥ 12 weeks before screening Participants who are current non‐smokers, who have not used inhaled tobacco products in the 12‐month period preceding screening visit Body weight ≥ 50 kg and BMI within the range 19.0 to 29.9 kg/m²	Yes, details not stated
NCT01134042	24	Pre‐bronchodilator FEV₁ 40% to 90% of predicted Reversibility FEV₁ ≥ 12%	Current asthma therapy that includes an ICS for ≥ 12 weeks before first visit Adults	Cortisol, ECG, mouth swabs, various blood parameters
NCT01453023	14	Mild to moderate (GINA)	Stable asthma therapy (FP, total daily dose ≤ 400 mcg or equivalent) and SABA inhaler for ≥ 4 weeks before screening 5 to 12 years of age Clinical diagnosis of asthma 6 months before Controlled asthma (Childhood ACT > 19)	Not stated
Oliver 2012	8	Pre‐bronchodilator FEV₁ > 70% of predicted at screening Methacholine challenge PC20 < 8 mg/mL at screening	Adults Stable asthma therapy (FP, total daily dose ≤ 400 mcg or equivalent) and SABA inhaler for ≥ 4 weeks before screening BMI within the range 18.5 to 35.0 kg/m²	Not stated
Oliver 2013	3 with 3 weeks' washout	Pre‐bronchodilator FEV₁ > 70% of predicted at screening Methacholine challenge PC20 < 8 mg/mL at screening	Stable asthma therapy (FP, total daily dose ≤ 400 mcg or equivalent) and SABA inhaler for ≥ 4 weeks before screening BMI within the range 18.5 to 35.0 kg/m² Adults	Not stated
Woodcock 2013	24	Reversibility ≥ 12% and 200 mL within 10 to 40 minutes following 2 to 4 inhalations of albuterol FEV₁ 40% to 85% predicted normal	Currently using ICS therapy Clinical diagnosis of asthma Adults	Not stated
ACT: Asthma Control Test AUC: area under the curve BMI: body mass index ECG: electrocardiogram FEV₁: forced expiratory volume in one second FP: fluticasone propionate GINA: Global Initiative for Asthma ICS: inhaled corticosteroid LABA: long‐acting beta₂‐agonist PC20: provocative concentration of methacholine estimated to result in a 20% reduction in FEV₁ SABA: short‐acting beta₂‐agonist

Table 1. Summary of study characteristics

Ir a la tabla de la revisión

Table 2. Health‐related quality of life

Study score (change from baseline)	FF/VI 100/25 mcg Mean (SE), N	FF 100 mcg Mean (SE), N	FF 200 mcg Mean (SE), N	FF/VI 200/25 mcg Mean (SE), N	FP/SAL 250/50 mcg twice‐daily	FP 500 mcg	Placebo	MD (95% CI)
Bleecker 2012 AQLQ change from baseline at 12 weeks	0.91 (0.055), n = 180	0.76 (0.055), n = 184	‐	‐	‐	‐	0.61 (0.061), n = 149	0.15 (0.00 to 0.30), 0.30 (0.14 to 0.46), 0.15 (‐0.01 to 0.31)
Lin 2013 AQLQ change from baseline at 12 weeks	‐	‐	‐	0.80 (0.069), n = 140	‐	0.69 (0.074), n = 123	‐	0.12 (‐0.08 to 0.32)
NCT01134042 AQLQ change from baseline at 12 weeks	‐	‐	0.66 (0.061), n = 154	0.74 (0.056), n = 180	‐	0.74 (0.059), n = 163	‐	‐0.08 (‐0.24 to 0.08), ‐0.08 (‐0.25 to 0.09), 0.00 (‐0.16 to 0.16)
NCT01134042 AQLQ change from baseline at 24 weeks	‐	‐	0.88 (0.071), n = 140	0.93 (0.065), n = 167	‐	0.90 (0.068), n = 156	‐	‐0.05 (‐0.24 to 0.14), ‐0.02 (‐0.21 to 0.17), 0.03 (‐0.15 to 0.21)
Woodcock 2013 AQLQ change from baseline at 168 days	0.46 (0.043), n = 342	‐	‐	‐	0.37 (0.043), n = 335	‐	‐	0.09 (‐0.03 to 0.21)
Woodcock 2013 EQ‐5D change from baseline at 168 days	5.5 (0.60), n = 343	‐	‐	‐	4.1 (0.60), n = 349	‐	‐	1.4 (‐0.3 to 3.0)
AQLQ: asthma quality of life questionnaire; CI: confidence interval; EQ‐5D: EuroQuality of Life‐5D questionnaire; FF: fluticasone furoate; FP: fluticasone propionate; MD: mean difference; SAL: salmeterol; SE: standard error; VI: vilanterol

Table 2. Health‐related quality of life

Ir a la tabla de la revisión

Table 3. Asthma exacerbation

Study	FF/VI 100/25 mcg	FF 100 mcg	FF 200 mcg	FF/VI 200/25 mcg	FP/SAL 250/50 mcg twice‐daily	FP 500 mcg	Prednisolone 10 mg	Placebo
Allen 2013^a 6 weeks' duration	0/56 (0.00%)	‐	‐	0/56 (0.00%)	‐	‐	0/15 (0.00%)	0/58 (0.00%)
Bateman 2014 ≥ 24 to 78 weeks' duration Time to first severe exacerbation (HR 0.80, 95% CI 0.64 to 0.99). Annualised rate of severe exacerbation 25% reduction (95% CI 5% to 40%)	154/1009 (15.26%)	186/1010 (18.42%)	‐	‐	‐	‐	‐	‐
Busse 2013 52 weeks' duration	3/201 (1.49%)	‐	‐	6/202 (2.97%)	‐	3/100 (3.00%)	‐	‐
Lin 2013 12 weeks' duration	‐	‐	‐	1/155 (0.65%)	‐	3/154 (1.95%)	‐	‐
Kempsford 2012 Cross‐over trial. Each period lasted 14 days with a 14 to 21‐day washout period between periods	0/24 (0.00%) AM 0/25 (0.00%) PM	‐	‐	‐	‐	‐	‐	0/23 (0.00%)
Woodcock 2013^b 24 weeks' duration	1/403 (0.25%)	‐	‐	‐	2/403 (0.50%)	‐	‐	‐
^aOne participant in the FF/VI 100/25 mcg group experienced a severe asthma exacerbation concurrent with sinusitis and was withdrawn owing to lack of efficacy. The participant did not require hospitalisation, and the event, which was not classified as an AE, resolved following treatment with prednisone ^bThe incidence of asthma exacerbations was low, and no difference was noted between groups (3% vs 2% on FP/SAL vs FF/VI, respectively (on‐treatment events)). Eight (2%) participants in the FF/VI group and seven (2%) in the FP/SAL group withdrew because of exacerbation. One patient in the FF/VI group and two in the FP/SAL group were hospitalised because of exacerbation AM: morning; CI: confidence interval; FF: fluticasone furoate; FP: fluticasone propionate; HR: hazard ratio; PM: afternoon; SAL: salmeterol; VI: vilanterol

Table 3. Asthma exacerbation

Ir a la tabla de la revisión

Table 4. Serious adverse events

Study	FF/VI 100/25 mcg	FF 100 mcg	FF 200 mcg	FF/VI 200/25 mcg	VI 25 mcg	FP/SAL 250/50 mcg twice‐daily	FP 500 mcg	Prednisolone 10 mg	Placebo
Allen 2013 6 weeks' duration. Post‐treatment period SAEs	0/56 (0.00%)	‐	‐	0/56 (0.00%)	‐	‐	‐	0/15 (0.00%)	0/58 (0.00%)
Bateman 2014 ≥ 24 to 78 weeks' duration. On‐treatment SAEs	41/1009 (4.06%)	29/1010 (2.87%)	‐	‐	‐	‐	‐	‐	‐
Bernstein 2014 12 weeks' duration	4/346 (1.16%)	3/347 (0.86%)	‐	1/346 (0.29%)	‐	‐	‐	‐	‐
Bleecker 2012 12 weeks' duration	0/201 (0.00%)	1/205 (0.49%)	‐	‐	‐	‐	‐	‐	0/203 (0.00%)
Busse 2013 52 weeks' duration. On‐treatment SAEs	3/201 (1.49%)	‐	‐	1/202 (0.50%)	‐	‐	7/100 (7.00%)	‐	‐
Lee 2014 Cross‐over trial. Three of 7 treatments (2 weeks) separated by 12 to 14‐day washout periods	1/172 (0.006%)	0/187 (0%)	‐	‐	‐	‐	‐	‐	‐
Lin 2013 12 weeks' duration	‐	‐	‐	1/155 (0.65%)	‐	‐	2/154 (1.30%)	‐	‐
Kempsford 2012 Cross‐over trial. Each period lasted 14 days with a 14 to 21‐day washout period	0/24 (0.00%) AM. 0/25 (0.00%) PM.	‐	‐	‐	‐	‐	‐	‐	0/23 (0.00%)
NCT01134042 24 weeks' duration	‐	‐	1/194 (0.52%)	6/197 (3.05%)	‐	‐	2/195 (1.03%)	‐	‐
NCT01453023 Cross‐over trial. 11 weeks (for a single period)	0/25 (0.00%)	0/25 (0.00%)	‐	‐	‐	‐	‐	‐	‐
Oliver 2012^a Cross‐over trial. 28 days for each period	0/51 (0.00%)	0/51 (0.00%)	‐	‐	‐	‐	‐	‐	0/51 (0.00%)
Oliver 2013 Cross‐over trial. 21 days	0/27 (0.00%)	0/27 (0.00%)	‐	‐	0/26 (0.00%)	‐	‐	‐	0/27 (0.00%)
Woodcock 2013 24 weeks' duration	4/403 (0.99%)	‐	‐	‐	‐	5/403 (1.24%)	‐	‐	‐
^aThe main paper reports that 1 of the 52 withdrew during the study owing to an SAE, which occurred 4 days after the last dose in the FF 100 treatment period. This participant was provisionally diagnosed with moderate (grade 2) Still’s disease. Six weeks later, the participant was hospitalised. A diagnosis of histiocytic necrotising lymphadenitis (Kikuchi’s disease) was made on the basis of histology of an excised lymph node. Tapered prednisolone treatment, initiated at 60 mg per day, has been successful FF: fluticasone furoate; FP: fluticasone propionate; SAE: serious adverse event; SAL: salmeterol; VI: vilanterol

Table 4. Serious adverse events

Ir a la tabla de la revisión

Table 5. Forced expiratory flow in one second (FEV1)

Study measure time point/ duration	FF/VI 100/25 mcg Mean (SE), N, of MD (95% CI)	FF 100 mcg Mean (SE), N	FF 200 mcg Mean (SE), N	FF/VI 200/25 mcg Mean (SE), N	VI 25 mcg Mean (SE), N	FP/SAL250/50 mcg twice‐daily Mean (SE), N	FP 500 mcg Mean (SE), N	Placebo Mean (SE), N	MD (95% CI, unless otherwise stated)
Bernstein 2014 Trough FEV₁ At 0 to 12 weeks Change in baseline trough FEV₁ from baseline to week 12	0.441 L (0.022)	0.365 L (0.022)	‐	0.457 L (0.022)	‐	‐	‐‐	‐	‐
Bleecker 2012 Trough FEV₁ At 0 to 12 weeks Mean change in trough FEV₁ (pre‐bronchodilator and pre‐dose) from baseline to week 12	0.368 L (0.0304), n = 200	0.332 L (0.0302), n = 203	‐	‐	‐	‐	‐	0.196 L (0.0310), n = 193	0.04 L (‐0.05 to 0.12) 0.17 L (0.09 to 0.26) 0.14 L (0.05 to 0.22)
Lee 2014 Trough FEV₁ combining all treatment periods At 0 to 2 weeks 3 of 7 treatments (2 weeks) separated by 12 to 14‐day washout periods	0.200 L, n = 158	0.087 L, n = 158	‐	‐	‐	‐	‐	‐	‐
Lin 2013 12 weeks' duration	‐	‐	‐	‐	‐	‐	‐	‐	Adjusted treatment difference 0.108 L (0.040 to 0.176)
Kempsford 2012 Weighted mean FEV₁ over the day At day 14 Weighted mean FEV₁, over 0 to 24 hours post dose at day 14 Cross‐over trial. Each period lasted 14 days with a 14 to 21‐day washout period	AM dose: 3.188 L (3.112 to 3.265), n = 24 PM dose: 3.233 L (3.159 to 3.306), n = 25	‐	‐	‐	‐	‐	‐	2.811 L (2.729 to 2.893), n = 20	AM vs placebo 0.377 L (90% CI 0.293 to 0.462) PM vs placebo 0.422 L (90% CI 0.337 to 0.507) AM vs PM ‐0.44 L (90% CI ‐0.125 to 0.36)
(Kempsford 2012) Day 14 pre‐treatment (trough) AM FEV₁ At day 14	AM dose: 3.191 L (3.087 to 3.295), n = 24 PM dose: 3.285 L (3.187 to 3.383), n = 25	‐	‐	‐	‐	‐	‐	2.788 L (2.684 to 2.892), n = 22	AM vs placebo 0.403 L (90% CI 0.272 to 0.533) PM vs placebo 0.496 L (90% CI 0.369 to 0.624) AM vs PM ‐0.094 L (90% CI ‐0.221 to 0.034)
(Kempsford 2012) Day 14 pre‐treatment (trough) PM FEV₁ At day 14	AM dose: 3.153 L (3.049 to 3.258), n = 24 PM dose: 3.188 L (3.088 to 3.288), n = 25	‐	‐	‐	‐	‐	‐	2.879 L (2.775 to 2.982), n = 23	AM vs placebo 0.275 L (90% CI 0.169 to 0.380) PM vs placebo 0.309 L (90% CI 0.205 to 0.413) AM vs PM ‐0.034 (90% CI ‐0.138 to 0.070)
NCT01134042 Change in baseline trough FEV₁ At 24 weeks Change from baseline in clinic visit trough (pre‐bronchodilator and pre‐dose) FEV₁ at end of 24‐week treatment period	‐	‐	0.201 L (0.0303), n = 186	0.394 L (0.0302), n = 187	‐	‐	0.183 L (0.0300), n = 190	‐	‐0.19 L (‐0.28 to ‐0.11) 0.02 L (‐0.06 to 0.10) 0.21 L (0.13 to 0.29)
(NCT01134042) Change from baseline in weighted mean serial FEV₁ over 24 hours At 24 weeks Change from baseline in weighted mean serial FEV₁ over 0 to 24 hours post dose at week 24	‐	‐	0.328 L (0.0493), n = 83	0.464 L (0.0470), n = 89	‐	‐	0.258 L (0.0483), n = 86	‐	‐0.14 L (‐0.27 to ‐0.00) 0.07 L (‐0.07 to 0.21) 0.21 L (0.07, 0.34)
Oliver 2012 23 hours post challenge At day 29 Cross‐over trial ‐ 28 days for each period Weighted mean change from baseline in FEV₁ between 0 and 2 hours following 22 to 23‐hour post‐treatment allergen challenge at day 29 of each treatment period	‐0.227 L (0.0550), n = 46	‐0.210 L (0.0549), n = 49	‐	‐	‐	‐	‐	‐0.372 L (0.0557), n = 45	FF vs placebo 0.162 L (0.087 to 0.237) FF/VI vs placebo 0.145 L (0.069 to 0.222) FF/VI vs FF ‐0.017 L (‐0.091 to 0.057)
(Oliver 2012) Decrease from baseline 23 hours post challenge At day 29 Maximum % decrease from baseline FEV₁ between 0 and 2 hours following 22 to 23‐hour post‐treatment allergen challenge at day 29 of each treatment period (time frame: baseline and at day 29 of each treatment period (up to study day 197))	‐13.206% (2.0491), n = 46	‐14.040% (2.0435), n = 49	‐	‐	‐	‐	‐	‐24.991% (2.0736), n = 45	FF vs placebo 10.951% (8.053 to 13.848) FF/VI vs placebo 11.785% (8.849 to 14.721) FF/VI vs FF 0.834% (‐2.010 to 3.678)
(Oliver 2012) Change from baseline FEV₁ 23 hours post challenge Minimum FEV₁ absolute change from baseline between 0 and 2 hours following 22 to 23‐hour post‐treatment allergen challenge at day 29 of each treatment period	‐0.478 L (0.0767), n = 46	‐0.479 L (0.0765), n = 49	‐	‐	‐	‐	‐	‐0.809 L (0.0775), n = 45	FF vs placebo 0.330 L (0.232 to 0.429) FF/VI vs placebo 0.331 L (0.231 to 0.43) FF/VI vs FF 0.001 L (‐0.096 to 0.097)
Oliver 2013 Change from baseline 4 to 10 hours post challenge At day 21 Cross‐over trial ‐ 21 days LAR: absolute change from baseline in minimum FEV₁ between 4 and 10 hours following 1‐hour post‐treatment allergen challenge at day 21 of each treatment period	‐0.216 L (‐0.343 to ‐0.088), n = 26	‐0.188 L (‐0.315 to ‐0.061), n = 27	‐	‐	‐0.536 L (‐0.676 to ‐0.396), n = 22	‐	‐	‐0.731 L (‐0.878 to ‐0.584), n = 20	‐
(Oliver 2013) Change from baseline 4 to 10 hours post challenge At day 21 LAR: absolute change from baseline in weighted mean FEV₁ between 4 and 10 hours following 1‐hour post‐treatment allergen challenge at day 21 of each treatment period	0.018 L (‐0.089 to 0.125), n = 26	0.018 L (‐0.089 to 0.124), n = 27	‐	‐	‐0.298 L (‐0.415 to ‐0.181), n = 22	‐	‐	‐0.466 L (‐0.589 to ‐0.343), n = 20	‐
Woodcock 2013 Change from baseline trough FEV₁ At day 168 24 weeks' duration	0.281 L (0.0191), n = 397	‐	‐	‐	‐	0.300 L (0.0193), n = 389	‐	‐	‐0.019 L (‐0.073 to 0.034)
AM: morning; CI: confidence interval; FEV₁: forced expiratory volume in one second; FF: fluticasone furoate; FP: fluticasone propionate; h: hour; LAR: late asthmatic response; MD: mean difference; PM: afternoon; SAL: salmeterol; SE: standard error; VI: vilanterol

Table 5. Forced expiratory flow in one second (FEV1)

Ir a la tabla de la revisión

Table 6. Peak expiratory flow

Study	Duration (weeks)	Measure of PEF	FF/VI 100/25 mcg Mean (SD, unless otherwise stated), N	FF 100 mcg Mean (SD, unless otherwise stated), N	FF 200 mcg Mean (SE), N	FF/VI 200/25 mcg Mean (SE ), N	FP 500 mcg Mean (SE), N	Placebo Mean (SE, unless otherwise stated), N	MD (95% CI, unless otherwise stated)
Bernstein 2014	12	Change from baseline, AM Change from baseline in AM PEF Averaged over 12‐week treatment period	44.3 L/min (2.25)	19.1 L/min (2.25)	‐	47.7 L/min (2.25)	‐		25.20 L/min (18.96 to 31.44), 100/25 vs 100 FF
Bernstein 2014	12	Change from baseline, PM Change from baseline in AM PEF Averaged over 12‐week treatment period	39.7 L/min (2.24)	15.5 L/min (2.24)	‐	41.7 L/min (2.24)	‐		24.20 L/min (17.99 to 30.41), 100/25 vs 100 FF
Bleecker 2012	12	Change from baseline, PM Mean change from baseline in daily PM PEF averaged over 12‐week treatment period	26.4 L/min (SE 2.35), n = 201	14.1 L/min (SE 2.34), n = 204	‐	‐	‐	‐1.8 L/min (2.36), n = 202	12.30 L/min (5.80 to 18.80), 28.20 L/min (21.67 to 34.73), 15.90 L/min (9.39 to 22.41)
Hojo 2015	4	Change from baseline, AM Only 1 (FF/VI) condition reported. Trial reported as conference abstract with limited information
Lee 2014	Baseline to day 15	Least squares mean change calculated from baseline to day 15 Least squares mean change in last 7 days, mean PEF	24.1 (2.46) AM 21.4 (2.58) PM n = 172	‐2.9 (2.44) AM ‐5.2 (2.51) PM n = 187	‐	‐	‐	‐	‐
Lin 2013	12	12 weeks' duration.	‐	‐	‐	39.1 L/min (3.01), n = 155	10.5 L/min (3.03), n = 154	‐	Adjusted treatment difference 28.5 L/min (20.1 to 36.9)
Kempsford 2012	12 days	Pre‐treatment Pre‐treatment PEF at days 1 to 12 Cross‐over trial. Each period lasted 14 days with a 14 to 21‐day washout period	AM dose: 510.4 L/min (95% CI 492.9 to 527.8), n = 24 PM dose: 535.3 L/min (95%CI 518.1 to 552.5), n = 25	‐	‐	‐	‐	466.3 L/min (95% CI 448.8 to 483.9), n = 24	AM vs placebo 44.0 L/min (90% CI 31.2 to 56.9) PM vs placebo 69.0 L/min (90% CI 55.9 to 82.1) AM vs PM ‐25.0 L/min (90% CI ‐37.9 to ‐12.0)
Kempsford 2012	12 days	Pre‐treatment Pre‐treatment PEF (PM) at days 1 to 12	AM dose: 517.6 L/min (95% CI 503.0 to 532.2), n = 24 PM dose: 521.4 L/min (95% CI 507.1 to 535.7), n = 26	‐	‐	‐	‐	453.2 L/min (95% CI 438.5 to 467.9), n = 24	AM vs placebo 64.4 L/min (90% CI 52.9 to 76.0) PM vs placebo 68.2 L/min (90% CI 56.5 to 79.8) AM vs PM ‐3.7 L/min (90% CI ‐15.2 to 7.7)
NCT01134042	24	Change from baseline, AM 4 weeks Mean change from baseline in daily trough (AM) PEF averaged over 24‐week treatment period	‐	‐	18.2 L/min (2.97), n = 193	51.8L/min (2.94), n = 197	18.8L/min (2.95), n = 195	‐	‐33.60 L/min (‐41.79 to, ‐25.41), ‐0.60 L/min (‐8.80 to 7.60), 33.00 L/min (24.84 to 41.16)
NCT01134042	24	Change from baseline, PM Mean change from baseline in daily trough (PM) PEF averaged over 24‐week treatment period	‐	‐	9.1 L/min (2.98), n = 192	39.8 L/min (2.93), n = 197	13.6 L/min (2.96), n = 194	‐	‐30.70 L/min (‐38.89 to ‐22.51), ‐4.50 L/min (‐12.73 to 3.73), 26.20 L/min (18.04 to 34.36)
AM: morning; CI: confidence interval; FF: fluticasone furoate; PEF: peak expiratory flow; PM: evening; SD: standard deviation; SE: standard error; VI: vilanterol

Table 6. Peak expiratory flow

Ir a la tabla de la revisión

Table 7. Asthma symptoms

Study	Measure	FF/VI 100/25 mcg Mean (SE)	FF 100 mcg Mean (SE)	FF 200 mcg Mean (SE)	FF/VI 200/25 mcg Mean (SE)	FP/SAL250/50 mcg twice‐daily Mean (SE)	FP 500 mcg Mean (SE)	Placebo Mean (SE)	MD (95% CI)
Bateman 2014 ≥ 24 to 78 weeks' duration Responder analysis results: ORs for FF/VI vs FF at week 12 (1.49, 95% CI 1.20 to 1.84), week 36 (1.49, 95% CI 1.21 to 1.83) and at endpoint (1.50, 95% CI 1.23 to 1.82)	ACQ7 mean difference and responder analysis	NR	NR	‐	‐	‐	‐	‐	‐
Bernstein 2014 Change from baseline in percentage of symptom‐free 24‐hour periods during 12‐week treatment	Change from baseline % symptom‐free days	27.2 (1.74) n = 345	19.4 (1.74) n = 346	‐	29.0 (1.74) n = 346	‐	‐	‐‐
Bleecker 2012 Change from baseline in % of symptom‐free 24‐hour periods during 12‐week treatment period	Change from baseline % symptom‐free days	32.5 (2.14), n = 201	20.4 (2.13), n = 204	‐	‐	‐	‐	14.6 (2.15), n = 202	12.10 (6.18 to 18.02), 17.90 (11.95 to 23.85), 5.80 (‐0.13 to 11.73)
Hojo 2015 Trial reported as conference abstract with limited information	Change from baseline ACT score
Lee 2014 LS mean change in symptom‐free days during 2‐week treatment period	LS mean change in symptom‐free days (SE)	7.3 (1.67) n = 172	5.8 (1.64) n = 187	‐	‐	‐	‐	‐	‐
Lin 2013 % of symptom‐free 24‐hour periods, weeks 1 to 12	% symptom‐free days	‐	‐	‐	25.4 (2.74), n = 155	‐	20.6 (2.77), n = 152	‐	4.9 (‐2.8 to 12.5)
NCT01134042 Change from baseline in ACT scores at week 12	Change from baseline ACT score	‐	‐	3.9 (0.29), n = 164	4.8 (0.27), n = 183	‐	3.9 (0.28), n = 169	‐	‐0.90 (‐1.68 to ‐0.12), 0.00 (‐0.79 to 0.79), 0.90 (0.14 to 1.66)
(NCT01134042) Change from baseline in ACT scores at week 24	Change from baseline ACT score	‐	‐	5.2 (0.30), n = 147	5.5 (0.28), n = 170	‐	4.7 (0.29), n = 162	‐	‐0.30 (‐1.10 to 0.50), 0.50 (‐0.32 to 1.32), 0.80 (0.01 to 1.59)
Woodcock 2013 Change from baseline in ACT scores at day 168 and at 24 weeks	Change from baseline ACT score	2.3 (0.16), n = 354	‐	‐	‐	2.0 (0.16), n = 348	‐	‐	0.2 (‐0.2 to 0.7)
ACT: asthma control test; CI: confidence interval; FF: fluticasone furoate; FP: fluticasone propionate; LS: least squares; MD: mean difference; NR: not reported; OR: odds ratio; SAL: salmeterol; SE: standard error; VI: vilanterol

Table 7. Asthma symptoms

Ir a la tabla de la revisión

Comparison 1. FF/VI 100/25 versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in quality of life (measured by AQLQ at 12 wk) Show forest plot	1	329	Mean Difference (Fixed, 95% CI)	0.3 [0.14, 0.46]

2 Exacerbations Show forest plot	2	161	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

3 Serious adverse events Show forest plot	5	721	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

4 FEV₁ Litres Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.17 [0.09, 0.26]

5 PEFR AM L/min (change from baseline at 12 wk) Show forest plot	1		Mean Difference (Fixed, 95% CI)	33.3 [26.59, 40.01]

6 PEFR PM L/min (change from baseline at 12 wk) Show forest plot	1		Mean Difference (Fixed, 95% CI)	28.2 [21.67, 34.73]

7 Change in asthma symptoms (measured by ACT) Show forest plot	1	339	Mean Difference (Fixed, 95% CI)	1.9 [1.22, 2.58]

Comparison 1. FF/VI 100/25 versus placebo

Ir a la tabla de la revisión

Comparison 2. FF/VI 100/25 versus same dose of FF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in quality of life (measured by AQLQ at 12 wk) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.15 [‐0.00, 0.30]

2 Exacerbations Show forest plot	2	2425	Odds Ratio (M‐H, Fixed, 95% CI)	1.38 [0.86, 2.22]

3 Serious adverse events Show forest plot	5	1258	Odds Ratio (M‐H, Fixed, 95% CI)	1.61 [0.42, 6.17]

4 Trough FEV₁ (L) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.08 [0.02, 0.14]

5 PEFR AM (change from baseline at 12 wk) Show forest plot	2		Mean Difference (Fixed, 95% CI)	20.29 [15.72, 24.85]

6 PEFR PM (change from baseline at 12 wk) Show forest plot	2		Mean Difference (Fixed, 95% CI)	18.52 [14.03, 23.01]

7 Change in asthma symptoms (measured by ACT) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.6 [‐0.04, 1.24]

Comparison 2. FF/VI 100/25 versus same dose of FF

Ir a la tabla de la revisión

Comparison 3. FF/VI 100/25 versus same dose VI

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Serious adverse events Show forest plot	1	53	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. FF/VI 100/25 versus same dose VI

Ir a la tabla de la revisión

Comparison 4. FF/VI 100/25 versus FP 500 µg

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Exacerbations Show forest plot	1	301	Odds Ratio (M‐H, Fixed, 95% CI)	0.49 [0.10, 2.47]

2 Serious adverse events Show forest plot	1	301	Odds Ratio (M‐H, Fixed, 95% CI)	0.20 [0.05, 0.80]

Comparison 4. FF/VI 100/25 versus FP 500 µg

Ir a la tabla de la revisión

Comparison 5. FF/VI 100/25 versus FPS 250/50 bd

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in quality of life (measured by AQLQ at 24 wk) Show forest plot	1	677	Mean Difference (Fixed, 95% CI)	0.09 [‐0.03, 0.21]

2 Exacerbations Show forest plot	1	806	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.05, 5.52]

3 Serious adverse events Show forest plot	1	806	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.21, 2.99]

4 FEV₁ Show forest plot	1		Mean Difference (Fixed, 95% CI)	‐0.02 [‐0.07, 0.03]

5 Change in asthma symptoms (measured by ACT) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.24 [‐0.20, 0.68]

Comparison 5. FF/VI 100/25 versus FPS 250/50 bd

Ir a la tabla de la revisión

Comparison 6. FF/VI 100/25 µg versus FF/VI 200/25 µg

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Exacerbations Show forest plot	2	515	Odds Ratio (M‐H, Fixed, 95% CI)	2.02 [0.50, 8.19]

2 Serious adverse events Show forest plot	2	515	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.18]

Comparison 6. FF/VI 100/25 µg versus FF/VI 200/25 µg

Ir a la tabla de la revisión

Comparison 7. FF/VI 200/25 versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Exacerbations Show forest plot	1	114	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

2 Serious adverse events Show forest plot	1	114	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

3 FEV₁ Litres Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.21 [0.13, 0.29]

4 Change in asthma symptoms (measured by ACT) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.9 [0.12, 1.68]

Comparison 7. FF/VI 200/25 versus placebo

Ir a la tabla de la revisión

Comparison 8. FF/VI 200/25 µg versus FP 500 µg

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in quality of life (measured by AQLQ at 12 wk) Show forest plot	2	606	Mean Difference (Fixed, 95% CI)	0.05 [‐0.08, 0.17]

2 Change in quality of life (measured by AQLQ at 24 wk) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.03 [‐0.15, 0.21]

3 OLD*Health‐related quality of life Show forest plot**	2	606	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.08, 0.17]

4 Exacerbations Show forest plot	2	611	Odds Ratio (M‐H, Fixed, 95% CI)	0.70 [0.22, 2.20]

5 Serious adverse events Show forest plot	3	1003	Odds Ratio (M‐H, Fixed, 95% CI)	0.61 [0.25, 1.49]

6 PEFR Show forest plot	1		Mean Difference (Fixed, 95% CI)	28.6 [20.23, 36.97]

7 PEFR AM Show forest plot	1		Mean Difference (Fixed, 95% CI)	33.0 [24.84, 41.16]

8 PEFR PM Show forest plot	1		Mean Difference (Fixed, 95% CI)	26.2 [18.04, 34.36]

9 % symptom‐free days Show forest plot	1		Mean Difference (Fixed, 95% CI)	4.8 [‐2.84, 12.44]

10 Change in asthma symptoms (measured by ACT) Show forest plot	1	332	Mean Difference (Fixed, 95% CI)	0.8 [0.01, 1.59]

Comparison 8. FF/VI 200/25 µg versus FP 500 µg

Ir a la tabla de la revisión

Comparison 9. FF/VI 200/25 versus same dose of FF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in quality of life (measured by AQLQ at 12 wk) Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.08 [‐0.08, 0.24]

2 Change in quality of life (measured by AQLQ at 24 wk) Show forest plot	1	307	Mean Difference (Fixed, 95% CI)	0.05 [‐0.14, 0.24]

3 Serious adverse events Show forest plot	1	391	Odds Ratio (M‐H, Fixed, 95% CI)	6.06 [0.72, 50.84]

4 FEV₁ Litres Show forest plot	1		Mean Difference (Fixed, 95% CI)	0.19 [0.10, 0.28]

5 PEFR AM Show forest plot	1		Mean Difference (Fixed, 95% CI)	33.6 [25.41, 41.79]

6 PEFR PM Show forest plot	1		Mean Difference (Fixed, 95% CI)	30.7 [22.51, 38.89]

7 Change in asthma symptoms (measured by ACT) Show forest plot	1	317	Mean Difference (Fixed, 95% CI)	0.3 [‐0.50, 1.10]

Comparison 9. FF/VI 200/25 versus same dose of FF

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet

Scolaris Content Display Scolaris Content Display

Temas

Scolaris Language Selector Scolaris Language Selector

Scolaris Content Display Scolaris Content Display

Instituciones a las que se accedió previamente

Scolaris Content Display Scolaris Content Display

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Contenido relacionado

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Temas

Copiar o descargar referencia

Idioma de la Revisión Cochrane

Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso