Captain: effects of age as a continuous variable on treatment outcomes

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: The CAPTAIN study showed that adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) led to improvements in lung function and symptom control in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). In a previous analysis of CAPTAIN, we showed that response to FF/UMEC/VI may vary according to patient age (<65 vs ≥65 years). Here, we further explore potential differential treatment responses using age as a continuous variable. METHODS: This Phase IIIA, double-blind, 24–52-week, parallel-group study randomized adults (no upper age limit) with uncontrolled asthma despite ICS/LABA therapy (N=2436). Treatment: once-daily FF/VI (100/25, 200/25mcg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, 200/62.5/25mcg) (ELLIPTA inhaler). Here we report post hoc analyses of change from baseline in clinic trough forced expiratory volume in 1 second (FEV1) at Week 24 (analyzed using mixed model repeated measures) and annualized rate of moderate/severe asthma exacerbations (Weeks 1–52; analyzed using a negative binomial model) according to patient age. Treatment groups were pooled by addition of UMEC 62.5mcg or FF dose. Fractional polynomial modelling was used to model the effect of age on each endpoint. RESULTS: Numerically greater improvements in trough FEV1 (~100mL) were seen following the addition of UMEC 62.5mcg to FF/VI irrespective of patient age. There was an indication that addition of UMEC 62.5mcg led to numerically greater reductions in moderate/severe exacerbation rate versus FF/VI with increasing age; however, the overlap in 95% confidence intervals was substantial. The higher FF dose (200mcg) was associated with numerical improvements in trough FEV1 versus FF 100mcg across the age range, although there was some overlap in 95% confidence intervals. Furthermore, the improvements in trough FEV1 with the higher dose of FF were less pronounced compared with the effect of adding UMEC. The higher FF dose was also associated with numerically greater reductions in moderate/severe exacerbation rate versus FF 100mcg across the age range. In all analyses there was greater uncertainty at the extremes due to lower numbers of patients. CONCLUSIONS: Addition of UMEC or use of the higher FF dose were generally associated with numerical improvements in treatment outcomes independent of age. CLINICAL IMPLICATIONS: Improvements observed with the addition of UMEC 62.5mcg to FF/VI or use of the higher FF dose were generally independent of age.Funding: GSK (205715/NCT02924688). DISCLOSURES: Employee relationship with GSK Please note: Aug 2017 - current Added 04/20/2021 by Zelie Bailes, source=Web Response, value=Salary Employee relationship with GSK Please note: Aug 2017 - current Added 04/20/2021 by Zelie Bailes, source=Web Response, value=Ownership interest Employee relationship with GSK Please note: >$100000 by Neil Barnes, source=Web Response, value=Shares Participation in multicenter clinical research trials relationship with AstraZeneca Please note: $20001 - $100000 by Louis-Philippe Boulet, source=Admin input, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Advisory Committee Member relationship with GSK Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Advisory Committee Member relationship with Merck Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Advisory Committee Member relationship with Novartis Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Advisory Committee Member relationship with Takeda Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Fees for consulting relationship with AstraZeneca Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Fees for consulting relationship with Merck Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Fees for consulting relationship with GSK Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Fees for consulting relationship with Metapharm Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Consulting fee Fees for consulting relationship with Novartis Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, 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- $20000 by Louis-Philippe Boulet, source=Admin input, value=Non profit grants Production of educational material relationship with GSK Please note: $20001 - $100000 by Louis-Philippe Boulet, source=Admin input, value=Non profit grants Production of educational material relationship with Merck Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Non profit grants Production of educational material relationship with Novartis Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Non profit grants Non profit grants relationship with Covis Please note: $5001 - $20000 by Louis-Philippe Boulet, source=Admin input, value=Grant/Research Support Employee relationship with GSK Please note: 2014-2021 Added 05/04/2021 by Frances Gardiner, source=Web Response, value=Salary Advisory Committee Member relationship with AstraZeneca, Genentech, GSK, Mylan, Sanofi Please note: 2020-2021 Added 04/20/2021 by Nicola Hanania, source=Web Response, 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