Potential treatment benefits and safety of roflumilast in COPD: a systematic review and meta-analysis

Figures & data

Table 1 Characteristics of included studies

Study	Design	Duration (weeks)	Grade (FEV1%/predict)/(FEV1/FVC)	Dosage	Patient number	Jadad score
Rabe et al^Citation9 (L)	R, DB	24	30%–80%	RO 250 mg/d	578	5
			<70%	Placebo	280
Rabe et al^Citation9 (H)	R, DB	24	30%–80%	RO 500 mg/d	555	5
			<70%	Placebo	280
Calverley et al^Citation10	R, DB	52	<50%	RO 500 mg/d	760	6
			<70%	Placebo	753
Calverley et al^Citation11 (M2-124)	R, DB	52	<50%	RO 500 mg/d	765	6
			<70%	Placebo	758
Claverley et al^Citation11 (M2-125)	R, DB	52	<50%	RO 500 mg/d	772	6
			<70%	Placebo	796
Fabbri et al^Citation12 (M2-127 [S])	R, DB	24	40%–70%	RO 500 mg/d	466	6
			<70%	Placebo	467
Fabbri et al^Citation12 (M2-128 [T])	R, DB	24	40%–70%	RO 500 mg/d	371	6
			<70%	Placebo	372
Rennard et al^Citation13 (M2-111)	R, DB	52	<50%	RO 500 mg/d	567	6
			<70%	Placebo	606
Rennard et al^Citation13 (M2-112)	R, DB	52	<50%	RO 500 mg/d	760	6
			<70%	Placebo	753
Lee et al^Citation14	R, DB	12	30%–80%	RO 500 mg/d	203	6
			<70%	Placebo	207
O’Donnell et al^Citation15	R, DB	12	30%–80%	RO 500 mg/d	127	6
			<70%	Placebo	123
Zheng et al^Citation16	R, DB	24	<50%	RO 500 mg/d	313	6
			<70%	Placebo	313
Martinez et al^Citation17	R, DB	52	<50%	RO 500 mg/d	969	6
			<70%	Placebo	966

Note: Items in brackets in the Study column are code names within the trial.

Abbreviations: FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; L, low; R, randomized; DB, double blind; RO, roflumilast; H, high; S, salmeterol; T, tiotropium.

Figure 1 Flowchart for identification of studies included in the meta-analysis.

Abbreviation: RCT, randomized clinical trial.

Figure 2 Pooled OR for COPD-related exacerbations (with 95% CI) of eligible studies comparing roflumilast with placebo.

Note: Items in brackets in the Study column are code names within the trial.
Abbreviations: OR, odds ratio; CI, confidence interval; M–H, Mantel–Haenszel; H, high; L, low.

Figure 3 Pooled mean change of FEV₁ from baseline prebronchodilator (with 95% CI) of eligible studies comparing roflumilast with placebo.

Note: Items in brackets in the Study column are code names within the trial.

Abbreviations: FEV₁, forced expiratory volume in the first second; CI, confidence interval; Std, standard; IV, instrumental variable; H, high; L, low; SD, standard deviation.

Figure 4 Pooled mean change of FEV₁ from baseline postbronchodilator (with 95% CI) of eligible studies comparing roflumilast with placebo.

Note: Items in brackets in the Study column are code names within the trial.
Abbreviations: FEV₁, forced expiratory volume in the first second; CI, confidence interval; IV, instrumental variable; H, high; L, low; SD, standard deviation.

Table 2 Analysis of adverse event

Adverse event	Pool study population						OR (95% CI)
	Roflumilast group			Placebo group
	Event	Total	Rate (%)	Event	Total	Rate (%)
Diarrhea	520	7,218	7.2	117	6,381	1.8	4.49 (3.16–6.38)
Nausea	250	7,015	3.6	67	6,174	1.1	3.82 (2.16–4.53)
Weight loss	335	5,313	6.3	85	5,348	1.5	4.07 (3.13–5.30)
Nasopharyngitis	524	6,903	7.6	344	6,070	5.6	0.96 (0.83–1.12)
Headache	190	6,087	3.1	76	6,101	1.2	2.4 (1.83–3.15)

Figure 5 Pooled OR for adverse event (with 95% CI) of eligible studies comparing roflumilast with placebo.

Note: Items in brackets in the Study column are code names within the trial.
Abbreviations: OR, odds ratio; CI, confidence interval; M–H, Mantel–Haenszel; H, high; L, low.

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