Treatment with budesonide/formoterol pressurized metered-dose inhaler in patients with asthma: a focus on patient-reported outcomes

Figures & data

Table 1 Designs for studies of budesonide/formoterol pMDI

Reference	N	Age	Asthma severity	Design	Duration	Treatment groups
Adolescents and adults
Noonan et al (NCT00652002)^Citation19	596	≥12 years	Moderate to severe	R, DB, double-dummy, PBO-controlled	12 weeks	BUD/FM pMDI 320/9 μg bid BUD pMDI 320 μg bid + FM DPI 9 μg bid BUD pMDI 320 μg FM DPI 9 μg bid PBO
Corren et al (NCT00651651)^Citation20	480	≥12 years	Mild to moderate	R, DB, double-dummy, PBO-controlled	12 weeks	BUD/FM pMDI 160/9 μg bid BUD pMDI 160 μg bid FM DPI 9 μg bid PBO
Peters et al (NCT00651768)^Citation21	708	≥12 years	Moderate to severe	R, DB, parallel-group, single-dummy	52 weeks	BUD/FM pMDI 640/18 μg bid BUD/FM pMDI 320/9 μg bid BUD pMDI 640 μg bid
Kerwin et al (NCT00646516)^Citation22	619	≥12 years	Mild to moderate	R, DB, parallel-group, single-dummy, active-controlled	12 weeks	BUD/FM pMDI 160/9 μg bid BUD/FM pMDI 320/9 μg qd BUD/FM pMDI 160/9 μg qd BUD pMDI 320 μg qd
Berger et al (NCT00652392)^Citation23	752	≥16 years	Mild to moderate	R, DB, double-dummy, PBO- and active-controlled	12 weeks	BUD/FM pMDI 160/9 μg bid BUD/FM pMDI 320/9 μg qd BUD/FM pMDI 160/9 μg qd BUD pMDI 320 μg qd PBO
Busse et al (NCT00646594)^Citation24	1225	≥12 years	Moderate to severe	R, open-label	7 months	BUD/FM pMDI 320/9 μg bid FP/SM DPI 250/50 μg bid Adjustable-dose BUD/FM pMDI
Children and adolescents
Murphy et al (NCT00651547)^Citation25	411	6–15 years	Mild to moderate	R, DB, double-dummy, active-controlled	12 weeks	BUD/FM pMDI 80/9 μg bid BUD pMDI 80 μg bid FM DPI 9 μg bid
Morice et al (SD-039–0682)^Citation26	622	6–11 years		R, DB, double-dummy, parallel-group	12 weeks	BUD/FM pMDI 160/9 μg bid BUD/FM DPI 160/9 μg bid BUD pMDI 200 μg bid
Berger et al (NCT00646529)^Citation27	187	6–11 years		R, open-label	26 weeks	BUD/FM pMDI 320/9 μg bid BUD DPI 400 μg bid
Eid et al (NCT00646321)^Citation28	522	6–15 years		R, DB, parallel-group, active-controlled	12 weeks	BUD/FM pMDI 80/9 μg bid BUD/FM pMDI 160/9 qd BUD pMDI 160 μg qd

Abbreviations: bid, twice daily; BUD, budesonide; DB, double-blind; DPI, dry powder inhaler; FM, formoterol; FP, fluticasone propionate; N, number of patients; PBO, placebo; pMDI, pressurized-metered dose inhaler; qd, once daily; R, randomized; SM, salmeterol.

Table 2 Efficacy of budesonide/formoterol pMDI in patients with asthma

	Predose FEV1 (L)^a	12-Hour mean FEV1	Morning PEF (L/min)	Evening PEF (L/min)	Symptom-free days (%)	Awakening-free nights (%)	Rescue medication use (inh/day)^b
Adolescents and adults	Mean change from baseline to end of treatment
Noonan et al^Citation19
BUD/FM pMDI 320/9 μg bid	0.19^Table Footnotec,Table Footnoted,Table Footnotee	0.37^Table Footnotec,Table Footnoted,Table Footnotee	35^Table Footnotec,Table Footnoted,Table Footnotee	34^Table Footnotec,Table Footnoted,Table Footnotee	23.1^Table Footnotec,Table Footnoted,Table Footnotee	12.7^e	−1.0^Table Footnoted,Table Footnotee
BUD pMDI 320 μg bid + FM DPI 9 μg bid	0.14	0.35	28	26	21.8	13.4	−1.5
BUD pMDI 320 μg	0.10	0.15	9	7	9.5	15.1	−0.8
FM DPI 9 μg bid	−0.12	0.17	−9	−7	2.9	9.4	−0.3
PBO	−0.17	−0.03	−18	−18	2.4	8.6	0.8
Corren et al^Citation20
BUD/FM pMDI 160/9 μg bid	0.37^Table Footnotec,Table Footnoted,Table Footnotee	0.50^Table Footnotec,Table Footnoted,Table Footnotee	54^Table Footnotec,Table Footnoted,Table Footnotee	40^Table Footnotec,Table Footnoted,Table Footnotee	26.5^Table Footnoted,Table Footnotee	21.6^e	−2.0^Table Footnoted,Table Footnotee
BUD pMDI 160 μg bid	0.23	0.32	24	17	29.8	22.2	−1.9
FM DPI 9 μg bid	0.17	0.41	21	16	18.1	18.5	−1.3
PBO	0.03	0.12	−4	0	7.5	12.8	0.2
Mean change from baseline to the average over the treatment period
Peters et al^Citation21
BUD/FM pMDI 640/18 μg bid	0.18^c	NA	40^c	NA	19.0^c	NA	−0.8^c
BUD/FM pMDI 320/9 μg bid	0.16^c	NA	34^c	NA	23.5^c	NA	−0.7^c
BUD pMDI 640 μg bid	0.08	NA	6	NA	5.9	NA	−0.2
Kerwin et al^Citation22
BUD/FM pMDI 160/9 μg bid	0.01^Table Footnotec,Table Footnotef,Table Footnoteg	NA	−1^c	0.3^Table Footnotec,Table Footnotef,Table Footnoteg	1.8^Table Footnotec,Table Footnotef,Table Footnoteg	−3.0^c	0.02^Table Footnotec,Table Footnotef,Table Footnoteg
BUD/FM pMDI 320/9 μg qd	−0.08^Table Footnotec,Table Footnotef	NA	−3^c	−12^c	−4.5^c	−2.7	0.16
BUD/FM pMDI 160/9 μg qd	−0.12^c	NA	−6^c	−16	−6.4	−1.9^c	0.18
BUD pMDI 320 μg qd	−0.18	NA	−22	−22	−11.0	−4.4	0.29
Berger et al^Citation23
BUD/FM pMDI 160/9 μg bid	−0.04^Table Footnotec,Table Footnotee	NA	1^Table Footnotec,Table Footnotee,Table Footnotef	1^Table Footnotec,Table Footnotee,Table Footnotef,Table Footnoteg	4.1^Table Footnotec,Table Footnotee,Table Footnotef	−2.3^Table Footnotec,Table Footnotee	−0.04^Table Footnotec,Table Footnotee,Table Footnotef,Table Footnoteg
BUD/FM pMDI 320/9 μg qd	−0.07^Table Footnotec,Table Footnotee	NA	−4^Table Footnotec,Table Footnotee	−14^Table Footnotec,Table Footnotee	−6.0 ^Table Footnotec,Table Footnotee,Table Footnotef	−2.3^Table Footnotec,Table Footnotee	0.21^Table Footnotec,Table Footnotee
BUD/FM pMDI 160/9 μg qd	−0.06^Table Footnotec,Table Footnotee	NA	−6^Table Footnotec,Table Footnotee	−14^Table Footnotec,Table Footnotee	−11.0^e	−2.6^Table Footnotec,Table Footnotee	0.26^e
BUD pMDI 320 μg qd	−0.20^e	NA	−30^e	−32^e	−16.2^e	−4.8^e	0.41^e
PBO	−0.31	NA	−43	−39	−27.5	−10.7	0.88
Busse et al^Citation24
BUD/FM pMDI 320/9 μg bid	0.15	NA	31	NA	25.8	10.0	−1.32
FP/SM DPI 250/50 μg bid	0.16	NA	34	NA	25.4	7.7	−1.30
Children and adolescents
Murphy et al^Citation25
BUD/FM pMDI 80/9 μg bid	0.07^c	NA	24^Table Footnotec,Table Footnoted	20^Table Footnotec,Table Footnoted	NA	NA	NA
BUD pMDI 80 μg bid	0.01	NA	8	6	NA	NA	NA
FM DPI 9 μg bid	0.03	NA	9	7	NA	NA	NA
Morice et al^Citation26
BUD/FM pMDI 160/9 μg bid	0.15	NA	30^c	24^c	34.9	NA	−0.50
BUD/FM DPI 160/9 μg bid	0.18	NA	30^c	26^c	37.4	NA	−0.54
BUD pMDI 200 μg bid	0.08	NA	20	18	35.2	NA	−0.42
Berger et al^Citation27
BUD/FM pMDI 320/9 μg bid	0.15^c	NA	NA	NA	NA	NA	NA
BUD DPI 400 μg bid	0.07	NA	NA	NA	NA	NA	NA
Eid et al^Citation28
BUD/FM pMDI 80/9 μg bid	−0.04^c	NA	8^c	7^c	−0.9	−1.8	0^Table Footnotec,Table Footnotef
BUD/FM pMDI 160/9 qd	−0.03^c	NA	4^c	0.5^c	−0.2	−2.4	0.08
BUD pMDI 160 μg qd	−0.11	NA	−5	−6	−3.7	−2.7	0.10

Notes:

a Predose FEV₁ was assessed in the evening for the Kerwin et al study; for all other studies, predose FEV₁ was assessed in the morning;^{19–23,27,28}

b Rescue medication use was presented as total inhalations (day and night) for all studies except the studies assessing once- versus twice-daily budesonide/formoterol pMDI, for which data are presented for the number of inhalations during the day (assessing the second half of the once-daily 24-hour dosing interval);^22,23,28

c P ≤ 0.05 vs BUD;

d P ≤ 0.05 vs FM DPI;

e P ≤ 0.05 vs PBO;

f P ≤ 0.05 vs BUD/FM pMDI 160/9 μg qd;

g P ≤ 0.05 vs BUD/FM pMDI 320/9 μg qd;

h All data from the study by Morice et al are presented as adjusted mean change from baseline values.

Abbreviations: bid, twice daily; BUD, budesonide; DPI, dry powder inhaler; FEV₁, forced expiratory volume in 1 second; FM, formoterol; FP, fluticasone propionate; NA, not assessed; PBO, placebo; PEF, peak expiratory flow; pMDI, pressurized-metered dose inhaler; qd, once daily; SM, salmeterol.

Figure 1 Onset of Effect Questionnaire: Percentage of patients who indicated that they could feel their study medication begin to work right away (A) and that they were satisfied with how quickly they felt their study medication begin to work (B).²⁹ Statistical analyses comparing FM DPI vs BUD pMDI and BUD pMDI + FM DPI vs BUD pMDI and PBO not performed in study I.

Notes: *P < 0.05 vs BUD pMDI; ^†P < 0.05 vs PBO. Copyright © 2008. Elsevier. Reprinted with permission from Kaiser H, Parasuraman B, Boggs R, Miller CJ, Leidy NK, O’Dowd L. Onset of effect of budesonide and formoterol administered via one pressurized metered-dose inhaler in patients with asthma previously treated with inhaled corticosteroids. Ann Allergy Asthma Immunol. 2008;101(3):295–303.²⁹
Abbreviations: BUD, budesonide; DPI, dry powder inhaler; FM, formoterol; PBO, placebo; pMDI, pressurized metered-dose inhaler.

Figure 2 Mean PSAM scores at the end of treatment in patients with (A) moderate to severe³¹ or (B) mild or moderate³² persistent asthma.

Notes: *P < 0.001 vs PBO; ^†P < 0.001 vs BUD; ^‡P < 0.005 vs FM. Copyright © 2008. Elsevier. Reprinted with permission from Chervinsky P, Baker J, Bensch G, et al. Patient-reported outcomes in adults with moderate to severe asthma after use of budesonide and formoterol administered via 1 pressurized metered-dose inhaler. Ann Allergy Asthma Immunol. 2008;101(5):463–473.³¹ Copyright © 2010. Oceanside Publications Inc. Korenblat PE, Rosenwasser LJ. Budesonide/formoterol pressurized metered-dose inhaler for patients with persistent asthma. Allergy Asthma Proc. 2010;31(3):190–202.⁴⁰
Abbreviations: BUD, budesonide; DPI, dry powder inhaler; FM, formoterol; PBO, placebo; pMDI, pressurized metered-dose inhaler; PSAM, Patient Satisfaction with Asthma Medication.

Figure 3 Adjusted mean change from baseline to end of treatment in AQLQ(S) overall and domain scores in patients with (A) moderate to severe³¹ or (B) mild to moderate³² persistent asthma.

Notes: A: *P < 0.01 vs PBO; ^†P < 0.05 vs BUD; ^‡P < 0.001 vs FM. B: *P < 0.001 vs PBO; ^†P < 0.001 vs FM; ^‡P < 0.05 vs PBO; ^§P < 0.05 vs FM. Copyright © 2008. Elsevier. Reprinted with permission from Chervinsky P, Baker J, Bensch G, et al. Patient-reported outcomes in adults with moderate to severe asthma after use of budesonide and formoterol administered via 1 pressurized metered-dose inhaler. Ann Allergy Asthma Immunol. 2008;101(5):463–473.³¹ Copyright © 2008. Informa Healthcare. Murphy K, Nelson H, Parasuraman B, Boggs R, Miller C, O’Dowd L. The effect of budesonide and formoterol in one pressurized metered-dose inhaler on patient-reported outcomes in adults with mild-to-moderate persistent asthma. Curr Med Res Opin. 2008;24(3): 879–894.³²

Abbreviations: AQLQ(S), Asthma Quality of Life Questionnaire (Standardized); BUD, budesonide; CI, confidence interval; DPI, dry powder inhaler; FM, formoterol; PBO, placebo; pMDI, pressurized metered-dose inhaler.

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