Figures
- FIGURE 1
Patient disposition and number of patients at selected time points during the PATENT-2 study.
- FIGURE 2
Mean change from baseline in 6-min walking distance (6MWD) in the PATENT-1 and PATENT-2 studies. Data are observed values and error bars represent standard error from the mean. #: Absolute value.
- FIGURE 3
The proportion of patients in whom World Health Organization functional class was improved, stabilised or worsened in the former riociguat 2.5 mg maximum patient group, the former riociguat 1.5 mg maximum patient group and the former placebo patient group. Data are observed values. Percentages may not add up to 100% due to rounding.
- FIGURE 4
Kaplan–Meier plots for a) clinical worsening and b) survival in the overall population during the PATENT-2 study. At 1 year, the estimated rate of clinical worsening-free survival was 88% (95% CI 84–91%) and the estimated survival rate was 97% (95% CI 94–98%). Using a worst-case analysis for clinical worsening, where patients who dropped out were assumed to have experienced clinical worsening, the rate of clinical worsening-free survival at 1 year was 84% (95% CI 80–87%). Using a worst-case analysis for survival, where patients who dropped out were assumed to have died, the rate of survival at 1 year was 90% (95% CI 87–93%).
Tables
- TABLE 1
Patient characteristics at the PATENT-1 study baseline
Characteristic Former riociguat 2.5 mg maximum Former riociguat 1.5 mg maximum Former placebo Total Patients n 231 56 109 396 Age years 50±16 48±16 49±16 50±16 Female 186 (81) 44 (79) 87 (80) 317 (80) Treatment naïve 114 (49) 30 (54) 53 (49) 197 (50) Pretreated 117 (51) 26 (46) 56 (51) 199 (50) PAH classification Idiopathic 136 (59) 35 (63) 74 (68) 245 (62) Familial 7 (3) 1 (2) 1 (1) 9 (2) Connective tissue disease-associated PAH 63 (27) 13 (23) 18 (17) 94 (24) Congenital heart disease-associated PAH 14 (6) 7 (13) 12 (11) 33 (8) Portal PH 10 (4) 0 2 (2) 12 (3) Anorexigen/amphetamine-associated PAH 1 (0.4) 0 2 (2) 3 (1) 6MWD m 364±67 359±68 378±66 367±67 WHO functional class I–IV patients n 231 56 108 395 I/II/III/IV 2/42/55/0# 7/30/63/0# 3/50/45/2 3/43/54/1# 100 101# Data are presented as mean±sd, n (%) or %, unless otherwise stated. PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; 6MWD: 6-min walking distance; WHO: World Health Organization. #: data does not add up to 100% due to rounding.
- TABLE 2
Adverse events (AE) in the PATENT-2 study
Former riociguat 2.5 mg maximum Former riociguat 1.5 mg maximum Former placebo Total Patients 231 56 109 396 Any AE 222 (96) 55 (98) 107 (98) 384 (97) Individual AEs in >10% of patients Nasopharyngitis 55 (24) 13 (23) 27 (25) 95 (24) Dizziness 53 (23) 12 (21) 28 (26) 93 (23) Peripheral oedema 50 (22) 14 (25) 25 (23) 89 (22) Cough 52 (23) 6 (11) 20 (18) 78 (20) Diarrhoea 32 (14) 11 (20) 27 (25) 70 (18) Headache 33 (14) 8 (14) 27 (25) 68 (17) Nausea 41 (18) 6 (11) 19 (17) 66 (17) Vomiting 30 (13) 8 (14) 19 (17) 57 (14) Upper respiratory tract infection 29 (13) 8 (14) 17 (16) 54 (14) Dyspnoea 28 (12) 11 (20) 12 (11) 51 (13) Dyspepsia 29 (13) 8 (14) 10 (9) 47 (12) Chest pain 26 (11) 6 (11) 14 (13) 46 (12) Epistaxis 22 (10) 10 (18) 12 (11) 44 (11) Drug-related AE 123 (53) 26 (46) 66 (61) 215 (54) Discontinued due to AE 25 (11) 4 (7) 7 (6) 36 (9) SAEs 114 (49) 30 (54) 60 (55) 204 (52) Discontinued due to SAE 18 (8) 4 (7) 7 (6) 29 (7) AEs of special interest in >5% of patients Hypotension 24 (10) 6 (11) 7 (6) 37 (9) Syncope 15 (6) 3 (5) 10 (9) 28 (7) Other AEs of interest Haemoptysis/pulmonary haemorrhage 16 (7) 2 (4) 7 (6) 25 (6) Data are presented as n or n (%). The mean treatment duration was 95 weeks. SAE: serious AE.
- TABLE 3
Change from the PATENT-1 study baseline during the PATENT-1 study and the PATENT-2 study
Former riociguat 2.5 mg maximum Former riociguat 1.5 mg maximum Placebo Total population PATENT-2 1 year PATENT-1 week 12 PATENT-2 PATENT-1 week 12 PATENT-2 PATENT-1 week 12 PATENT-2 Week 12 1 year Week 12 1 year Week 12 1 year NT-proBNP Observed values pg mL-1 −338±1031 −322±1206 −291±1612 −447±954 −520±944 −235±1214 134±809 −410±1023 −294±1945 −284±1653 Patients 207 201 177 46 46 44 95 93 80 301 Borg dyspnoea score Observed values −0.55±1.52 −0.58±1.84 −0.52±1.98 −0.43±1.19 −0.52±1.64 −0.18±1.58 −0.15±1.88 −0.54±1.90 −0.45±2.06 −0.45±1.94 Patients 228 218 192 55 54 49 108 102 84 325 EQ-5D score Observed values 0.05±0.21 0.06±0.22 0.06±0.24 0.10±0.26 0.15±0.24 0.13±0.24 0.02±0.22 0.03±0.24 0.07±0.20 0.07±0.23 Patients 227 212 193 55 52 50 106 102 83 326 LPH score Observed values −7.6±16.8 −11.0±18.9 −11.8±16.1 −14.3±18.9 −2.7±15.1 −2.1±15.7 Patients 224 209# 55 54# 105 93# Data are presented as mean±sd or n. NT-proBNP: N-terminal prohormone of brain natriuretic peptide; EQ-5D: Euro Qol Group 5-Dimension Self-Report Questionnaire. #: Week 8 data shown for Living with Pulmonary Hypertension (LPH) score.
- TABLE 4
Clinical worsening events during PATENT-2
Former riociguat Former placebo Total 2.5 mg maximum 1.5 mg maximum Patients 231 56 109 396 Patients with clinical worsening# 49 (21) 11 (20) 24 (22) 84 (21) Heart/lung transplantation 1 (0.4) 1 (2) 0 2 (1) Hospitalisation due to PH 25 (11) 5 (9) 11 (10) 41 (10) Start of new PH treatment 34 (15) 9 (16) 17 (16) 60 (15) Decrease in 6MWD due to PH 6 (3) 1 (2) 3 (3) 10 (3) Persistent worsening in WHO FC due to PH 4 (2) 0 1 (1) 5 (1) Died 14 (6) 4 (7) 9 (8) 27 (7) Data are presented as n or n (%). PH: pulmonary hypertension; 6MWD: 6-min walking distance; WHO: World Health Organization; FC: functional class. #: one patient can experience more than one type of event. The mean treatment duration was 95 weeks.
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