Results from the 1-year outcome period from matched cohorts comparing a step-up in asthma therapy, using either an increased dose of extrafine-particle ICS, or a fine-particle ICS/LABA combination inhaler versus the addition of LABA to ICS in a separate inhaler
| Outcome | Extrafine ICS step-up | p-valueƒ | FDC fine-particle ICS | p-valueƒ | ||
| ICS step-up | Separate ICS+LABA | FDC ICS/LABA | Separate ICS+LABA | |||
| Subjects n | 3232 | 6464 | 7529 | 15 058 | ||
| Risk-domain asthma control | 2436 (75.4) | 4573 (70.7) | <0.001 | 5408 (71.8) | 10 170 (67.5) | <0.001 |
| Severe exacerbation | ||||||
| 0 | 2692 (83.3) | 5101 (78.9) | <0.001 | 6110 (81.2) | 11 441 (76.0) | <0.001 |
| 1 | 393 (12.2) | 925 (14.3) | 971 (12.9) | 2313 (15.4) | ||
| 2 | 85 (2.6) | 259 (4.0) | 268 (3.6) | 726 (4.8) | ||
| ≥3 | 62 (1.9) | 179 (2.8) | 180 (2.4) | 578 (3.8) | ||
| Acute respiratory events | ||||||
| 0 | 2464 (76.2) | 4656 (72.0) | <0.001 | 5495 (73.0) | 10 350 (68.7) | <0.001 |
| 1 | 528 (16.3) | 1196 (18.5) | 1343 (17.8) | 2939 (19.5) | ||
| 2 | 143 (4.4) | 355 (5.5) | 404 (5.4) | 976 (6.5) | ||
| ≥3 | 97 (3.0) | 257 (4.0) | 287 (3.8) | 793 (5.3) | ||
| Treatment stability | 2111 (65.3) | 3487 (53.9) | <0.001 | 4626 (61.4) | 7862 (52.2) | <0.001 |
| ≥1 asthma-related hospital attendance | 10 (0.3) | 50 (0.8) | 0.008 | 29 (0.4) | 82 (0.5) | 0.11 |
| ≥1 antibiotic prescriptions for LRTI | 387 (12.0) | 815 (12.6) | 0.56 | 1050 (13.9) | 2063 (13.7) | 0.99 |
| ≥1 prescription for oral corticosteroids | 530 (16.4) | 1343 (20.8) | <0.001 | 1385 (18.4) | 3557 (23.6) | <0.001 |
| Treatment change# | 589 (18.2) | 1814 (28.1) | <0.001 | 1433 (19.0) | 4087 (27.1) | <0.001 |
| Increase in ICS dose¶ | 98 (3.0) | 1294 (20.0) | <0.001 | 1141 (15.2) | 2445 (16.2) | 0.034 |
| Additional therapy | 581 (18.0) | 1385 (21.4) | <0.001 | 469 (6.2) | 3344 (22.2) | <0.001 |
| ICS dose exposure μg·day−1¶ | 274 (164–438) | 155 (65–247) | <0.001 | 197 (115–345) | 192 (96–329) | 0.008 |
| Daily SABA dose μg·day−1 | 219 (110–548) | 219 (110–438) | <0.001 | 219 (110–438) | 274 (110–548) | <0.001 |
| Daily β2-agonist coverage h+ | 3.3 (1.1–7.7) | 10.4 (5.1–19.1) | <0.001 | 19.3 (10.5–28.7) | 11.8 (5.9–20.3) | <0.001 |
| Change from baseline h | 0.6 (−0.5–2.3) | 7.0 (2.9–14.7) | <0.001 | 15.2 (7.4–23.7) | 7.6 (2.9–15.2) | <0.001 |
| Spacer device prescribed | 486 (15.0) | 1182 (18.3) | <0.001 | 985 (13.1) | 2926 (19.4) | <0.001 |
| Oropharyngeal candidiasis§ | 155 (4.8) | 321 (5.0) | 0.72 | 396 (5.3) | 819 (5.4) | 0.57 |
Data are presented as n (%) or median (interquartile range), unless otherwise stated. ICS: inhaled corticosteroids; LABA: long-acting β2-agonist; FDC: fixed-dose combination; LRTI: lower respiratory tract infection; SABA: short-acting β2-agonist. #: patients could have more than one change in therapy (and both increased ICS dose and additional therapy) during the year. Additional therapy could include combination ICS/LABA inhaler (for ICS step-up cohort), separate LABA inhaler, leukotriene receptor antagonist and theophylline; ¶: the dose of budesonide was halved for equivalence with extrafine beclomethasone and fluticasone, for which actual doses were used in the analyses. Daily ICS dose exposure was calculated as the dispensed amount divided by 365. In the separate ICS+LABA cohort, 9–10% of patients were prescribed extrafine beclomethasone during the baseline period and 10–11% during the outcome period; +: defined as the dispensed amount divided by 365 and defining two puffs of SABA as lasting 4 h, and two puffs of LABA via pressurised metered-dose inhaler or one puff of LABA via dry powder inhaler as lasting 12 h; §: diagnosis of or therapy for oropharyngeal candidiasis (thrush); : p-value for conditional logistic regression.