The efficacy of extrafine beclomethasone dipropionate–formoterol fumarate in COPD patients who are not “frequent exacerbators”: a post hoc analysis of the FORWARD study

Figures & data

Table 1 COPD exacerbations and predose morning FEV₁ at week 12: BDP-FF versus FF overall in GOLD B and D patients (intention-to-treat population)

Group	n	COPD exacerbations: adjusted rate ratio*	Predose morning FEV1 (mL): adjusted mean difference*
Overall	1,186	0.69 (0.59–0.81; P<0.001)	69 (43–95; P<0.001)
Tiotropium	616 (51.9%)	0.68 (0.55–0.84; P<0.001)	48 (14–82; P=0.006)
No tiotropium	570 (48.1%)	0.70 (0.56–0.88; P=0.003)	90 (50–129; P<0.001)
Analysis 1
GOLD B	716 (60.4%)	0.65 (0.52–0.81; P<0.001)	69 (36–103; P<0.001)
Tiotropium	370 (31.2%)	0.54 (0.41–0.72; P<0.001)	52 (8–96; P=0.021)
No tiotropium	346 (29.2%)	0.76 (0.54–1.07; P=0.119)	85 (35–136; P=0.001)
GOLD D	313 (26.4%)	0.75 (0.58–0.95; P=0.017)	79 (33–125; P<0.001)
Tiotropium	169 (14.2%)	0.87 (0.62–1.22; P=0.419)	66 (6–127; P=0.033)
No tiotropium	144 (12.1%)	0.62 (0.44–0.87; P=0.006)	90 (20–161; P=0.013)
Analysis 2
GOLD B	662 (55.8%)	0.65 (0.52–0.82; P<0.001)	69 (36–102; P<0.001)
Tiotropium	359 (30.3%)	0.58 (0.43–0.78; P<0.001)	49 (6–92; P=0.027)
No tiotropium	303 (25.5%)	0.70 (0.49–1.01; P=0.054)	94 (42–145; P<0.001)
GOLD D	301 (25.4%)	0.74 (0.58–0.94; P=0.012)	83 (37–128; P<0.001)
Tiotropium	163 (13.7%)	0.85 (0.6–1.21; P=0.366)	61 (6–115; P=0.030)
No tiotropium	138 (11.6%)	0.63 (0.46–0.86; P=0.004)	101 (25–177; P=0.010)

Notes:

* 95% CI and P-value in parentheses. Number of COPD exacerbations and predose morning FEV₁ analyzed using a negative binomial model and MMRM, respectively. Analysis 1 used SGRQ score ≥25 to identify patients corresponding to GOLD B. Analysis 2 used dyspnea questions within the SGRQ to identify patients corresponding to GOLD B.

Abbreviations: FEV₁, forced expiratory volume in 1 second; BDP-FF, beclomethasone dipropionate–formoterol fumarate; FF, formoterol fumarate; SGRQ, St George’s Respiratory Questionnaire.

Figure 1 Adjusted exacerbation rates (per patient/year) for analysis 1 in GOLD B and GOLD D patients.

Abbreviations: BDP-FF, beclomethasone dipropionate–formoterol fumarate; FF, formoterol fumarate.

Figure 2 Adjusted exacerbation rates (per patient/year) for analysis 2 in GOLD B and GOLD D patients.

Abbreviations: BDP-FF, beclomethasone dipropionate–formoterol fumarate; FF, formoterol fumarate.

Table S1 IECs/IRBs for recruitment wave 1

Country	Center, type	IEC/IRB name, address
Austria	CEC/LEC	Gesundheitsdienst der Stadt Wien Ethikkommission der Stadt Wien 8 Thomas-Klestil-Platz, Vienna 1030
	LEC Graz	Ethik-Kommission der Medizinischen Universität Graz 2 Auenbruggerplatz, Graz 8036
	LEC Linz	Ethikkommission am Krankenhaus der Elisabethinen 2 Fadingerstrasse, Linz 4010
Czech Republic	CEC/LEC	Etická Komise Fakultní Nemocnice v Motole 84 V Úvalu, 150 06 Prague 5
Germany	CEC/LEC	Landesamt für Gesundheit und Soziales
	Berlin	Ethik-Kommission des Landes Berlin 1 Fehrbelliner Platz, Berlin 10707
	LEC Baden-Württemberg	Ethikkommission der Landesärztekammer Baden-Württemberg Körperschaft des öffentlichen Rechts 40 Jahnstrasse, Stuttgart 70597
	LEC Bayern	Ethikkkommission der Landesärztekammer Bayern 16 Mühlbauerstrasse München 81677
UK	MREC	Professor Wellman Berkshire Research Ethics Committee Building L27, University of Reading, London Road, Reading RG1 5AQ
	MHRA	Information Processing Unit Area 6, Medicines & Healthcare Products Regulatory Agency, Market Towers, 1 Nine Elms Lane, London SW8 5NQ

Abbreviations: IECs, institutional ethics committees; IRBs, institutional review boards.

Table S2 IECs/IRBs for recruitment wave 2

Country	Center, type	IEC/IRB name, address, chair (if applicable)
Argentina	CEC	Comité Independiente de Etica para Ensayos en Farmacología Clínica – FEFYM 774 Pte JE Uriburu, 1 Piso – CABA (C1027AAP) Dr Luis Zieher
	320001	Comité de Docencia de Investigación French 2673, CABA, C1425AWC Clelia Haydee Magaril
	32002	NA
	32003	Comité de Docencia e Investigación (CDI) San Martín de Tours 2926 – CABA (1425) Dr Gustavo Badariotti
	32004 IRB	Servicio de Investigación de Patologías Alérgicas del Instituto ABC 2668 Salta, Rosario, Santa Fe (S2000JKR) Dr Alejandro Garcia
	32005	NA
Australia	36001	Southern Adelaide Clinical Human Research Ethics Committee
	HREC	The Flats, G5 – rooms 3 and 4 Flinders Drive, Flinders Medical Centre, Bedford Park, SA 5042 Professor Gordan
	36002, 36003,	BellBerry Human Research Ethics Committee
	36004, 36005	229 Greenhill Road, Dulwich, SA 5065
	HREC	Brian Stoffell
Chile	152001	Comité Etico Cientifico Servicio de Salud Oriente
	152002	364 Avenida Salvador, Providencia, RM
	CEC	Dr Andres Stuardo
	152003	Comité Etico Cientifico Servicio de Salud Metropolitano Sur
	CEC	3453 Avenida Santa Rosa, RM Veronica Rivera
	152006	Comité Etico Cientifico Servicio de Salud Coquimbo
	CEC	795 Avenida Francisco Aguirre, La Serena Dr Buillermo Valdebenito
	152009	Comité Etico Cientifico del Servicio de Salud del Maule
	CEC	1 Norte – 963, 2000 Edificio Centro, Piso Talca Dr Rafael Muñoz
New Zealand	All sites	Multi-region Ethics Committee Ministry of Health, 133 Molesworth Street, PO Box 5013, Wellington 6145 Richman Wee
South Africa	710001	University of Cape Town, Health Science Faculty Research Ethics Committee Room E52-24, Groote Schuur Hospital, Old Main Building Observatory, Cape Town 7925 Professor M Blockman
	710004	University of Stellenbosch, Faculty of Health Sciences Health Research Ethics Committee PO Box 19063, Tygerberg 7505 Dr J Meintjies
	All other sites	Pharma Ethics 123 Amcor Road, Lytelton Manor, Pretoria 0157 Dr C Duvenage

Abbreviations: IECs, institutional ethics committees; IRBs, institutional review boards.

Table S3 IECs/IRBs for recruitment wave 3

Country	Center, type	IEC/IRB name, address, chair (if applicable)
Bulgaria	MEC/CEC	Ethics Committee for Multicenter Clinical Trials 8 Damian Gruev Street; Sofia 1303 Dr Anastas Stoykov
Czech Republic	MEC	Multicentric Ethics committee 84 FN Motol V Úvalu, 150 06 Prafue 5 Chair Vratislav Smeihaus
	203007	Regionalní Etická Komise Nemocnice Tábor
	LEC	2000 Kapitána Jaroše, Tábor 390 03 Ladislav Douda
France	CEC	Comité de Protection des Personnes CPP Ile de France III, Hopital Tarnier-Cochin 89 rue d’Assas, Paris 75006 Professor Boris Christoforov
Germany	276001	Landesamt für Gesundheit und Soziales
	276016	Ethik-Kommission des Landes Berlin 1 Fehrbelliner Platz Berlin 10707 Dr Hans-Herbert Fulle
	276013	Ethikkkommission der Landesärztekammer Sachsen
	276014	16 Schützenhöhe, Dresden 01099
	276015	Professor Habil R Haupt
	276005	Ethikkommission der Landesärztekammer Baden-Württemberg Körperschaft des öffentlichen Rechts 40 Jahnstrasse, Stuttgart 70597 Dr Georg Hook
	276016	Ethikkommission der Ärztekammer Niedersachsen 20 Berliner Allee, Hannover 30175 Dr Gisbert Voigt
	276012	Ethikkommission der Ärztekammer Westfalen-Lippe und der Medizinischen Fakultät der Westfälischen Wilhelms-Universität 210–214 Gartenstrasse, Münster 48147 Professor Hans-Werner Bothe
Hungary	All sites	Egeszsegugyi Tudomanyos Tanacs Klinikai Farmakologiai Etikai Bizottsaga 6–8 Ulitsa Arany János, Budapest 1051 Dr Zsussanna Furst
Italy	380001	Comitato per la Sperimentazione Clinica dei Medicinali dell’Azienda Ospedaliero Universitaria Pisana di Pisa 67 Via Roma, Pisa 56126
	380002	Comitato Etico per la Sperimentazione Clinica dei Medicinali dell’Azienda Ospedaliera Universitaria Integrata di Verona 1 Piazzale A Stefani, Verona 37126
	380003	Comitato Etico per la Sperimentazione Clinica dei Medicinali dell’Azienda Ospedaliero- Universitaria Careggi di Firenze 3 Largo Brambilla, Florence 50134
	380004	Comitato Etico Centrale Dell’Irccs Fondazione Salvatore Maugeri Di Pavia, 4 via Salvatore Maugeri, Pavia 27100
The Netherlands	528001	Medisch Ethische Toetsingscommissie Eindhoven Catharina-Ziekenhuis, Secretariaat METC 2 Michelangelolaan 2, Eindhoven 5623 MJH Stoffelen-Bruurs
	528002	Elkerliek Ziekenhuis, locatie Helmond METC, 25 Wesselmanlaan, Helmond 5707 Mr Corbeij
	528003	METC Noord-Holland Foreest Medical School 10 Nassauplein, Alkmaar 1815 B Blijham
	528004	Commissie WMO METC Noord-Holland, Foreest Medical School 10 Nassauplein, Alkmaar 1815
Poland	All sites	Komisja Bioetyczna Przy Okręgowej Izbie Lekarskiej w Warszawie 18 Ulitsa Puławska, Warsaw 02-512 Dr Marek Czarkowski
Romania	All sites	48 Aviator Sanatescu Street, Sector 1, Bucharest 011478 Professor Sava Dumitrescu
Spain	724002	Dr F Javier Abad Gimeno Secretario del Comité Ético de Investigación Servicio de Farmacia, planta 1. Avenida Ramón y Cajal, Puerto de Sagunto, Valencia 46520
	724003	Comité Etico de Investigación Clínica del Hospital General Universitario de Elche, Lorena Montolio Beltran 11 Camí de l’Almazara – 3, Planta del Edificio Anexo II, Elche, Alicante 03203
	724004	Paz Lavilla/Emma Fernández de Uzquiano Hospital General Planta, 261 Paseo de la Castellana, Madrid 28046
	724005	Hospital Clinic i Provicial–Comité Etico de Investigación Clínica/Villarroel, 170 Sótano – Escalera 6b, Barcelona 08036
Turkey	792-001	Mersin University Health Research and Practice Hospital Ihsaniye Mah, 4903 Sokak – 3 Necdet Unger Binası 3, Mersin 33079 Professor Bahar Tunctan
	MEC	Ministry of Health General Directorate of Pharmaceuticals and Pharmacy 2176 Söğütözü Mahallesi – 5 PK Çankaya, Ankara 06520 Hilal Ilbars
The UK	All sites	Berkshire Research Ethics Committee Building L27, University of Reading, London Road, Reading RG1 5AQ

Abbreviations: IECs, institutional ethics committees; IRBs, institutional review boards.