Patient-reported outcomes and considerations in the management of COPD: focus on aclidinium

Figures & data

Figure 1 Relationship between the severity of airflow limitation and breathlessness as assessed by the mMRC questionnaire (panel A), exercise capacity as assessed by the 6MWD (panel B), reported exacerbations in the year before inclusion in the study (panel C), and health status as assessed by the SGRQ-C (panel D).

Notes: Copyright ©2010. Agusti A, Calverley PM, Celli B, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122.⁸
Abbreviations: mMRC, modified Medical Research Council; SGRQ-C, St George’s Respiratory Questionnaire – COPD specific; 6MWD, 6-minute walking distance.

Table 1 Inhaled drugs for asthma and COPD

	LABA	LAMA	Inhaled steroids
12 hours	Salmeterol	Aclidinium	Beclomethasone
	Formoterol	Darotropium	Budesonide
			Fluticasone propionate
24 hours	Indacaterol	Tiotropium	Ciclesonide
	Vilanterol	Glycopyrronium	Mometasone
	Olodaterol	Umeclidinium	Fluticasone furoate
	Abediterol
	Carmoterol

Abbreviations: COPD, chronic obstructive pulmonary disease; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist.

Table 2 Principal patient-reported scales and questionnaires for COPD

Dyspnea	MRC scale^Citation23
	Borg scale^Citation60
	Basal/Transition Dyspnea Index (BDI–TDI)^Citation24
	Visual analog scale^Citation61
Health-related quality of life and symptom impact	Chronic Respiratory Disease Questionnaire (CRQ)^Citation62
	St George’s Respiratory Questionnaire (SGRQ)^Citation63
	COPD Assessment Test (CAT)^Citation64
	Clinical COPD Questionnaire (CCQ)^Citation65
	Living with COPD questionnaire^Citation66
	Global Chest Symptoms Questionnaire (GCSQ)^Citation67
	Capacity of Daily Living during the Morning questionnaire (CDLM)^Citation67
	Patient-centered COPD Questionnaire (PCQ)^Citation68
Cough and sputum	Leicester Cough Questionnaire^Citation69
	Cough and Sputum Assessment Questionnaire (CASA-Q)^Citation27
Sleep disturbances or nighttime symptoms	COPD and Asthma Sleep Impact Scale (CASIS)^Citation70
	Night-time Symptoms of COPD Instrument (NiSCI)^Citation71
Fatigue	Fatigue Impact Scale^Citation72
	Manchester COPD fatigue scale^Citation73

Notes: These are the most extended questionnaires for each area. Recently published comprehensive reviews on fatigue,⁷⁴ dyspnea,⁷⁵ and health-related quality of life⁷⁶ are available for the interested reader.

Abbreviations: COPD, chronic obstructive pulmonary disease; MRC, Medical Research Council.

Figure 2 Change from baseline in the TDI focal score over 24 weeks.

Notes: Data are presented as least squares mean ± standard error. Values on or above the dotted line represent clinically significant improvement. **P<0.01; ^#P<0.001 vs placebo. Copyright © European Respiratory Society. Reproduced and modified with permission of the European Respiratory Society. Eur Respir J. 2012;40:830–836; published ahead of print March 22, 2012, doi:10.1183/09031936.00225511.³⁵
Abbreviations: TDI, Transition Dyspnea Index; SGRQ, St George’s Respiratory Questionnaire; bid, twice daily.

Table 3 Summary of efficacy outcomes of aclidinium bromide 400 μg vs placebo from the two main pivotal studies

	ACCORD I		ATTAIN
	Placebo (n=186)	Aclidinium 400 μg (n=190)	Placebo (n=273)	Aclidinium 400 μg (n=269)
Trough FEV1 (mL)	Ref	124	Ref	128
Peak FEV1 (mL)	Ref	192	Ref	209
Dyspnea (TDI)	Ref	1.0	Ref	1.0
Rescue medication use (puffs/day)	Ref	0.9	Ref	0.95
Quality of life (SGRQ)	Ref	−2.5	Ref	−4.6

Notes: Data are expressed as mean values at the end of each study from baseline over placebo, which is marked as reference.

Abbreviations: FEV₁, forced expiratory volume in 1 second; TDI, Transition Dyspnea Index; SGRQ, St George’s Respiratory Questionnaire; Ref, reference.

Table 4 Adverse effects of aclidinium vs placebo in the ATTAIN and ACCORD COPD I studies

	ACCORD I		ATTAIN
	Placebo (n=186)	Aclidinium 400 μg (n=190)	Placebo (n=273)	Aclidinium 400 μg (n=269)
Any adverse effect	97 (52.2)	85 (44.7)	156 (57.1)	144 (53.5)
Any severe effect	4 (2.2)	6 (3.2)	15 (5.5)	15 (5.6)
Anticholinergic effects	<2	<2	2 (0.7)	2 (0.7)
Local adverse effects
COPD exacerbation	23 (12.4)	14 (7.4)	50 (20.5)	38 (14.1)
Dyspnea	6 (3.2)	5 (2.6)	–	–
Cough	5 (2.7)	4 (2.1)	5 (1.8)	7 (2.6)
Dry mouth	<2	<2	0.4	0.4
Oropharyngeal pain	3 (1.6)	4 (2.1)	–	–
Nasopharyngitis	2 (1.1)	3 (1.6)	23 (8.4)	30 (11.2)
Upper respiratory tract infection	7 (3.8)	2 (1.1)	–	–
Bronchitis	4 (2.2)	0 (0)	6 (2.2)	7 (2.6)
Influenza	–	–	6 (2.2)	3 (1.1)
Rhinitis	–	–	7 (2.6)	9 (3.3)
Toothache	–	–	1 (0.4)	6 (2.2)
Systemic adverse effects
Arthralgia	1 (0.5)	5 (2.6)	6 (2.2)	3 (1.1)
Diarrhea	3 (1.6)	4 (2.1)	3 (1.1)	8 (3.0)
Fatigue	4 (2.2)	4 (2.1)	–	–
Headache	4 (2.2)	3 (1.6)	22 (8.1)	33 (12.3)
Insomnia	6 (3.2)	3 (1.6)	–	–
Urinary tract infection	4 (2.2)	3 (1.6)	2 (0.7)	2 (0.7)
Back pain	1 (0.5)	3 (1.6)	10 (3.7)	5 (1.9)
Nausea	4 (2.2)	2 (1.1)	–	–
Dizziness	1 (0.5)	2 (1.1)	–	–
Hypertension	–	–	9 (3.3)	7 (2.6)
Dyspepsia	–	–	6 (2.2)	1 (0.4)

Notes: Data are expressed in absolute (relative) frequencies, except for anticholinergic effects in ACCORD I study, which are expressed as percentages.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 3 Change from baseline in the SGRQ total score over 24 weeks.

Notes: Data are presented as least squares mean ± standard error. Values on or below the dotted line represent clinically significant improvement. **P<0.01; ***P<0.001 vs placebo. Copyright © European Respiratory Society. Reproduced and modified with permission of the European Respiratory Society. Eur Respir J. 2012;40:830–836; published ahead of print March 22, 2012, doi:10.1183/09031936.00225511.³⁵
Abbreviations: SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index; bid, twice daily.

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