The European respiratory journal · 2024
Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Wechsler Michael E, Brusselle Guy, Virchow J Christian, Bourdin Arnaud, Kostikas Konstantinos, Llanos Jean-Pierre, Roseti Stephanie L, Ambrose Christopher S, Hunter Gillian, Jackson David J, Castro Mario, Lugogo Njira, Pavord Ian D, Martin Neil, Brightling Christopher E
Аннотация
BACKGROUND: In asthma, clinical response is characterised by disease improvement with treatment, whereas clinical remission is characterised by long-term disease stabilisation with or without ongoing treatment. The proportions of patients receiving tezepelumab who responded to treatment and who achieved on-treatment clinical remission were assessed in the NAVIGATOR (ClinicalTrials.gov identifier NCT03347279) and DESTINATION (ClinicalTrials.gov identifier NCT03706079) studies of severe, uncontrolled asthma.
METHODS: NAVIGATOR and DESTINATION were phase 3, randomised, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physician's assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed.
RESULTS: Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR 2.83, 95% CI 2.10-3.82) and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR 1.44, 95% CI 0.95-2.19) and weeks >52-104 (33.5% versus 26.7%; OR 1.44, 95% CI 0.97-2.14). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarker levels at baseline, and fewer exacerbations in the 12 months before the study.
CONCLUSIONS: Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes, but may be driven by different patient characteristics.
METHODS: NAVIGATOR and DESTINATION were phase 3, randomised, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physician's assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed.
RESULTS: Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR 2.83, 95% CI 2.10-3.82) and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR 1.44, 95% CI 0.95-2.19) and weeks >52-104 (33.5% versus 26.7%; OR 1.44, 95% CI 0.97-2.14). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarker levels at baseline, and fewer exacerbations in the 12 months before the study.
CONCLUSIONS: Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes, but may be driven by different patient characteristics.