Figures
- FIGURE 1
Flowchart of patients from the Danish Severe Asthma Register categorised as complete responders and noncomplete responders. IL: interleukin; OCS: oral corticosteroids.
- FIGURE 2
Proportion of patients who were complete responders after 12 months of anti-interleukin-5 treatment.
- FIGURE 3
Change in secondary outcomes in complete responders and noncomplete responders after 12 months of anti-interleukin-5 treatment: a) Asthma Control Questionnaire (ACQ) ≤1.5, b) forced expiratory volume in 1 s (FEV1) >80% predicted, c) exhaled nitric oxide fraction (FENO), d) blood eosinophils, e) FEV1 and f) ACQ score. *: significant difference (p<0.05) in change from baseline to 12 months between complete responders and noncomplete responders.
- FIGURE 4
Baseline predictors of complete response to anti-interleukin-5 treatment after 12 months. mOCS: maintenance oral corticosteroids; ACQ: Asthma Control Questionnaire; OSA: obstructive sleep apnoea.
Tables
- TABLE 1
Patient characteristics at baseline
n Baseline Age, years 502 57±12 Female 502 244 (47) BMI, kg·m−2 498 27.8±5.6 Duration of disease, years 308 22±18 Duration of disease >10 years 308 194 (63) Age at onset, years 308 35±21 Onset during childhood ≤18 years 321 93 (29) Late onset ≥40 years 321 144 (45) Exacerbations in year before biologic, n 391 3.08±3.1 Budesonide-equivalent dose, μg 350 1600 (1600–1600) mOCS 502 187 (37) Median dose, mg 137 10 (5–15) Biologic 502 Mepolizumab 355 (71) Reslizumab 26 (5) Benralizumab 121 (24) Switchers 502 129 (26) FEV1, L 436 2.23±0.85 FEV1, % pred 432 69±21 FEV1/FVC 421 0.65±0.13 ACQ score 312 2.48±1.29 Blood eosinophils, ×109 L−1 415 0.32 (0.12–0.6) Blood eosinophils ≥0.3×109 L−1 415 227 (55) IgE, IU·mL−1 258 128 (55–350) IgE ≥150 IU·mL−1 258 119 (46) FENO, ppb 352 32 (17–64) Smoking status 486 Never-smoker 252 (52) Ex-smoker 225 (46) Current smoker 9 (2) Pack-years 292 17.7±13.8 Allergic rhinitis 480 214 (46) Atopic dermatitis 476 63 (13) Chronic rhinosinusitis 474 275 (58) Nasal polyps 478 208 (44) Aspirin sensitivity 475 39 (8) Bronchiectasis 478 99 (21) Vocal cord dysfunction 471 10 (2) ABPA 475 14 (3) EGPA 473 20 (6) Dysfunctional breathing 474 27 (6) COPD 470 116 (25) GORD 474 146 (31) Cardiovascular disease 475 149 (31) Diabetes 477 55 (12) OSA 475 55 (12) Data are presented as mean±sd, n (%) or median (interquartile range), unless otherwise stated. BMI: body mass index; mOCS: maintenance oral corticosteroids; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ACQ: Asthma Control Questionnaire; FENO: exhaled nitric oxide fraction; ABPA: allergic bronchopulmonary aspergillosis; EGPA: eosinophilic granulomatosis with polyangiitis; COPD: chronic obstructive pulmonary disease; GORD: gastro-oesophageal reflux disease; OSA: obstructive sleep apnoea.
- TABLE 2
Outcomes after 1 year of treatment with anti-interleukin-5 biologics for severe asthma
n Baseline n 1 year p-value Clinical outcomes Exacerbations in previous 12 months, n 391 3.08±3.1 391 0.62±1.27 <0.0001 mOCS 502 187 (37) 502 123 (25) <0.0001 Median dose, mg 63 10 (7.5–15) 63 7.5 (5–10) <0.0001 Budesonide-equivalent dose, µg 297 1600 (1600–2000) 297 1600 (1200–1600) <0.0001 FEV1, L 365 2.25±0.85 365 2.37±0.88 <0.0001 FEV1, % pred 362 69±21 362 74±21 <0.0001 FEV1/FVC 347 0.65±0.13 347 0.66±0.12 0.0007 FEV1 >80% 362 110 (30) 362 140 (39) 0.0001 ACQ score 242 2.49±1.31) 242 1.61±1.21 <0.0001 ACQ ≤1.5 242 67 (28) 242 132 (55) <0.0001 Biomarkers Blood eosinophils, ×109 L−1 280 0.31 (0.12–0.60) 282 0.06 (0.02–0.10) <0.0001 FENO, ppb 280 35 (18–65) 280 30 (16–59) 0.01 Data are presented as mean±sd, n (%) or median (interquartile range), unless otherwise stated. mOCS: maintenance oral corticosteroids; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ACQ: Asthma Control Questionnaire; FENO: exhaled nitric oxide fraction. Only patients with paired data at baseline and 12 months are included.
- TABLE 3
Complete responder versus noncomplete responder characteristics at baseline
n Complete responders (n=289) n Noncomplete responders (n=213) p-value Age, years 289 58±12 213 56±13 0.12 Female 289 129 (45) 213 115 (54) 0.038 BMI, kg·m−2 287 28±5 211 28±6 0.28 Duration of disease, years 179 20±17 129 24±19 0.04 Duration of disease >10 years 179 107 (60) 129 87 (67) 0.169 Age at onset, years 179 38±20 129 32±21 0.02 Onset during childhood ≤18 years 186 46 (25) 135 47 (35) 0.131 Late onset ≥40 years 186 90 (48) 135 54 (40) 0.131 Exacerbations in year before biologic, n 219 2.80±2.61 172 3.43±3.61 0.049 Budesonide-equivalent dose, µg 195 1600 (1200–1600) 155 1600 (1600–2000) 0.23 mOCS 289 52 (18) 213 134 (63) <0.0001 Median dose, mg 46 7.5 (5–10) 91 10 (7.5–15) 0.03 Biologic 289 213 0.125 Mepolizumab 207 (72) 148 (69) Reslizumab 10 (3) 16 (8) Benralizumab 72 (25) 49 (23) Switchers 289 66 (23) 213 63 (29) 0.08 FEV1, L 248 2.26±0.85 188 2.18±0.83 0.31 FEV1, % pred 246 70±21 186 68±21 0.41 FEV1/FVC 237 0.64±0.13 184 0.65±0.13 0.70 ACQ score 168 2.32±1.32 144 2.67±1.24 0.01 Blood eosinophils, ×109 L−1 234 0.40 (0.18–0.65) 181 0.23 (0.1–0.54) 0.0002 Blood eosinophils ≥0.3×109 L−1 234 146 (62) 181 81 (45) 0.0003 IgE, IU·mL−1 146 141 (66–399) 112 70 (54–83) 0.09 IgE ≥150 IU·mL−1 146 71 (49) 112 48 (43) 0.35 FENO, ppb 201 32 (18–64) 151 32 (14–63) 0.65 Smoking status 281 205 0.62 Never-smoker 151 (54) 101 (49) Ex-smoker 125 (44) 100 (49) Current smoker 5 (2) 4 (2) Pack-years 15.9±13 17.7±14.4 0.33 Allergic rhinitis 277 132 (48) 203 82 (41) 0.11 Atopic dermatitis 274 37 (14) 202 26 (13) 0.84 Chronic rhinosinusitis 273 166 (61) 201 109 (54) 0.15 Nasal polyps 276 122 (44) 202 86 (43) 0.72 Aspirin sensitivity 274 27 (10) 201 12 (6) 0.13 Bronchiectasis 276 53 (19) 202 46 (23) 0.34 Vocal cord dysfunction 272 5 (2) 199 5 (3) 0.61 ABPA 275 9 (3) 200 5 (3) 0.62 EGPA 273 11 (4) 200 9 (5) 0.80 Dysfunctional breathing 273 17 (6) 201 10 (5) 0.56 COPD 270 61 (23) 200 55 (28) 0.22 GORD 272 83 (31) 202 63 (31) 0.87 Cardiovascular disease 274 82 (30) 201 67 (33) 0.42 Diabetes 275 25 (9) 202 30 (15) 0.05 OSA 273 26 (10) 202 29 (14) 0.10 Data are presented as mean±sd, n (%) or median (interquartile range), unless otherwise stated. BMI: body mass index; mOCS: maintenance oral corticosteroids; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ACQ: Asthma Control Questionnaire; FENO: exhaled nitric oxide fraction; ABPA: allergic bronchopulmonary aspergillosis; EGPA: eosinophilic granulomatosis with polyangiitis; COPD: chronic obstructive pulmonary disease; GORD: gastro-oesophageal reflux disease; OSA: obstructive sleep apnoea.
- TABLE 4
Outcomes for complete versus noncomplete responders after 1 year of treatment with anti-interleukin-5 biologics
Complete responders Noncomplete responders Δ complete versus Δ noncomplete responders p-value Clinical outcomes Exacerbations in previous 12 months, n 0.008 At baseline 2.80±2.61 3.43±3.61 At 12 months 0 1.48±1.71 p-value <0.0001 <0.0001 mOCS <0.0001 At baseline 53 (18) 134 (63) At 12 months 0 123 (58) p-value <0.0001 0.0009 Budesonide-equivalent dose, µg 0.0006 At baseline 1600 (1200–1600) 1600 (1600–2000) At 12 months 1600 (800–1600) 1600 (1600–2000) p-value 0.002 0.17 FEV1, L <0.0001 At baseline 2.26±0.85 2.18±0.83 At 12 months 2.47±0.87 2.21±0.85 Δ from baseline 0.21 0.03 p-value <0.0001 0.63 FEV1, % pred <0.0001 At baseline 70±21 68±21 At 12 months 76±20 70±22 Δ from baseline 6 2 p-value <0.0001 0.20 FEV1/FVC 0.014 At baseline 0.64±0.13 0.65±0.13 At 12 months 0.67±0.10 0.65±0.13 p-value <0.0001 0.69 FEV1 >80% 0.008 At baseline 31 31 At 12 months 44 31 p-value <0.0001 1.00 ACQ score 0.016 At baseline 2.32±1.32 2.67±1.24 At 12 months 1.28±1.11 1.99±1.26 Δ from baseline −1.04 −0.68 p-value <0.0001 <0.0001 ACQ ≤1.5 <0.0001 At baseline 33 21 At 12 months 67 40 p-value <0.0001 0.0006 Biomarkers Blood eosinophils, ×109 L−1 <0.0001 At baseline 0.40 (0.18–0.65) 0.23 (0.1–0.54) At 12 months 0.06 (0.02–0.10) 0.06 (0.02–0.10) p-value <0.0001 <0.0001 FENO, ppb 0.71 At baseline 32 (18–64) 32 (14–63) At 12 months 29 (16–54) 30 (16–60) p-value 0.04 0.14 Data are presented as mean±sd, n (%), % or median (interquartile range), unless otherwise stated. mOCS: maintenance oral corticosteroids; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ACQ: Asthma Control Questionnaire; FENO: exhaled nitric oxide fraction.
