Treatment of Chronic Obstructive Pulmonary Disease with Roflumilast, a New Phosphodiesterase 4 Inhibitor

Figures & data

Figure 1.  Structures of roflumilast and its primary metabolite roflumilast N-oxide.

Figure 2.  Probability of treatment discontinuation in roflumilast and placebo groups in trials M2–124 (A) and M2–125 (B). Reproduced from Calverley PMA et al Lancet 2009;374:685–94 with permission. *Number of patients still at risk at the beginning of the respective week; number at risk might be different from the number completing the study because the protocol allowed patients to finish the study up to 7 days before the end of week 52.

Figure 3.  Prebronchodilator and postbronchodilator forced expiratory volumes in 1 s (FEV₁) over 52 weeks in patients in roflumilast and placebo groups in trials M2–124 (A) and M2–125 (B), and changes in prebronchodilator and postbronchodilator FEV₁ over 52 weeks in patients in roflumilast and placebo groups in trials M2–124 (C) and M2–125 (D). Error bars are SE. Reproduced from Calverley PMA et al Lancet 2009;374:685–94 with permission.

Table 3.  Adverse events occurring in at least 2·5% of patients in one of the treatment groups of the M2–124 and M2–125 studies

	M2–124			M2–125*
	Roflumilast (n = 769)†	Placebo (n = 755)†	Roflumilast vs. placebo (difference, 95% CI)	Roflumilast (n = 778)†	Placebo (n = 790)†	Roflumilast vs. placebo (difference, 95% CI)
COPD	70 (9%)	82 (11%)	−1.76% (−4.90 to 1.38)	87 (11%)	122 (15%)	−4.26% (−7.74 to −0.78)
Diarrhea	63 (8%)	26 (3%)	4.75% (2.28 to 7.21)	67 (9%)	23 (3%)	5.70% (3.28 to 8.12)
Weight loss	92 (12%)	24 (3%)	8.78% (6.04 to 11.53)	65 (8%)	20 (3%)	5.82% (3.46 to 8.18)
Nasopharyngitis	57 (7%)	50 (7%)	0.79% (−1.91 to 3.49)	35 (5%)	47 (6%)	−1.45% (−3.78 to 0.88)
Upper respiratory tract infection	16 (2%)	21 (3%)	−0.70% (−2.38 to 0.98)	33 (4%)	38 (5%)	−0.57% (−2.75 to 1.62)
Headache	26 (3%)	17 (2%)	1.13% (−0.66 to 2.92)	25 (3%)	8 (1%)	2.20% (0.65 to 3.75)
Pneumonia	17 (2%)	15 (2%)	0.22% (−1.35 to 1.79)	25 (3%)	16 (2%)	1.19% (−0.52 to 2.90)
Back pain	27 (4%)	22 (3%)	0.60% (−1.30 to 2.50)	23 (3%)	13 (2%)	1.31% (−0.30 to 2.92)
Acute bronchitis	35 (5%)	40 (5%)	−0.75% (−3.05 to 1.56)	21 (3%)	24 (3%)	−0.34% (−2.12 to 1.44)
Nausea	41 (5%)	15 (2%)	3.34% (1.34 to 5.35)	21 (3%)	15 (2%)	0.80% (−0.81 to 2.41)
Hypertension	20 (3%)	28 (4%)	−1.11% (−2.99 to 0.78)	18 (2%)	20 (3%)	−0.22% (−1.87 to 1.43)
Insomnia	19 (2%)	8 (1%)	1.41% (−0.04 to 2.86)	18 (2%)	12 (2%)	0.79% (−0.69 to 2.28)
Decreased appetite	21 (3%)	2 (<1%)	2.47% (1.13 to 381)	15 (2%)	5 (<1%)	1.30% (0.05 to 2.54)
Influenza	27 (4%)	18 (2%)	1.13% (−0.70 to 2.95)	12 (2%)	20 (3%)	−0.99% (−2.51 to 0.53)

Data are number (%), unless otherwise indicated. Adverse events were reported independently of the investigator causality assessments. Patients might have had more than one adverse event. COPD = chronic obstructive pulmonary disease. *Incidence of adverse events in roflumilast-treated patients in study M2–125 is in a descending order. †One patient was randomized twice and included twice in the safety analysis but only once in the efficacy analysis; four patients assigned to placebo were given roflumilast instead and were included in the roflumilast group for the safety analysis; 765 patients in the roflumilast group and 758 in the placebo group were included in the efficacy analysis. ‡Six patients assigned to placebo were given roflumilast instead and were included in the roflumilast group for safety analysis; 772 patients in the roflumilast group and 796 in the placebo group were included in the efficacy analysis. Reproduced from Calverley PMA et al Lancet 2009;374:685–94 with permission.