Use of a 4-week up-titration regimen of roflumilast in patients with severe COPD

Figures & data

Figure 1 Patient disposition.

Notes: ^aA pre-treatment event is defined as any untoward medical occurrence in a patient who had signed written informed consent to participate in a study, but prior to administration of any study medication; it did not necessarily have to have a causal relationship with study participation.
Abbreviations: EOD, every other day; LTFU, lost to follow-up; OD, once daily; ROF, roflumilast; 250, 250 µg; 500, 500 µg.

Table 1 Baseline patient characteristics

Characteristics	ROF 250 OD/ROF 500 OD (n=441)	ROF 500 EOD/ROF 500 OD (n=437)	ROF 500 OD (n=443)
Age, years	64.2 (7.8)	65.0 (8.2)	64.6 (8.4)
Male, n (%)	320 (72.6)	325 (74.4)	338 (76.3)
White, n (%)	405 (91.8)	399 (91.3)	405 (91.4)
BMI, kg/m^2	26.4 (6.0)	26.01 (5.6)	26.46 (5.9)
Cigarette pack years	38.1 (17.5)	40.2 (19.2)	37.6 (17.7)
Current smoker, n (%)	213 (48.3)	198 (45.3)	196 (44.2)
Pre-bronchodilator FEV1, L	1.0 (0.3)	1.0 (0.3)	1.0 (0.3)
Pre-bronchodilator FVC, L	2.3 (0.7)	2.3 (0.7)	2.3 (0.7)
% predicted FEV1	36.0 (8.8)	36.7 (8.8)	36.0 (9.5)
Post-bronchodilator FEV1/FVC	0.46 (0.1)	0.47 (0.1)	0.46 (0.1)
% FEV1 reversibility	7.1 (12.0)	6.45 (14.4)	7.4 (11.4)
≤2 exacerbations, n (%)	435 (98.6)	427 (97.7)	432 (97.5)
>2 exacerbations, n (%)	6 (1.4)	9 (2.1)	9 (2.0)
Most commonly reported concomitant medication, n (%)a	440 (99.8)	437 (100.0)	443 (100.0)
LAMA (tiotropium bromide)	245 (55.6)	235 (53.8)	225 (50.8)
ICS/LABA (seretide, budesonide)	202 (45.8)	197 (45.0)	217 (48.9)
Theophylline	80 (18.1)	85 (19.5)	80 (18.1)

Notes: Data are taken from the SAS and expressed as mean (SD) unless otherwise stated.

a Taken in ≥10% of all patients.

Abbreviations: BMI, body mass index; EOD, every other day; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; OD, once daily; ROF, roflumilast; SAS, safety analysis set; SD, standard deviation; 250, 250 µg; 500, 500 µg.

Figure 2 (A) Probability of patients continuing the 12-week trial for any reason (SAS). (B) Percentage of patients discontinuing for any reason.

Abbreviations: CI, confidence interval; EOD, every other day; OD, once daily; OR, odds ratio; ROF, roflumilast; SAS, safety analysis set; 250, 250 µg; 500, 500 µg.

Figure 3 Summary of AEs of interest.

Note: Percentage of patients with ≥1 AE to evaluate tolerability.
Abbreviations: AE, adverse event; CI, confidence interval; EOD, every other day; OD, once daily; OR, odds ratio; ROF, roflumilast; 250, 250 µg; 500, 500 µg.

Figure 4 Mean change in body weight.

Notes: Measurements are mean, with bars showing SD. Vend was the last measurement obtained before dropout/study completion.
Abbreviations: EOD, every other day; OD, once daily; ROF, roflumilast; SD, standard deviation; 250, 250 µg; 500, 500 µg.

Figure 5 Comparison of tPDE4i levels achieved with ROF 500 µg or 250 µg according to whether patients were able to tolerate the dose.

Notes: Medians in trial and down-titration phase. ^aFor consistency with previous popPK models, the list of preferred terms included in the AEs of interest for the popPK model is larger than that used to investigate safety in this study (Table S7). Error bars are 95% CI.
Abbreviations: AE, adverse event; CI, confidence interval; OD, once daily; popPK, population pharmacokinetics; ROF, roflumilast; tPDE4i, total phosphodiesterase-4 inhibitory activity; 250, 250 µg; 500, 500 µg.