In patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, the use of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs FF/VI and UMEC/VI was associated with improved exacerbation rates, lung function, and health status, regardless of the patient’s smoking status, according to study findings published in Respiratory Medicine.
In a post hoc analysis of the IMPACT trial (ClinicalTrials.gov Identifier: NCT02164513), investigators sought to determine whether smoking status affects treatment outcomes by assessing the efficacy and safety of FF/UMEC/VI vs FF/VI and UMEC/VI in patients with COPD who currently and formerly smoked.
The randomized, double-blind, 52-week phase 3 IMPACT study compared the efficacy and safety of once-daily single-inhaler triple therapy with FF/UMEC/VI 100/62.5/25 mcg with once-daily dual therapy with FF/VI 100/25 μg or UMEC/VI 62.5/25 μg. The post hoc analysis evaluated the efficacy and safety of triple therapy compared with dual therapy by smoking status at screening.
Participants were at least 40 years of age with symptomatic COPD (COPD Assessment Test score ≥10) and either: (1) a forced expiratory volume in 1 second (FEV1) of less than 50% of predicted normal values and at least 1 moderate or severe exacerbation in the previous year; or (2) FEV1 50% to 80% of predicted normal values and at least 2 moderate or at least 1 severe exacerbation within the previous year.
Efficacy endpoints included the rate of moderate/severe exacerbations while on treatment; risk of moderate/severe exacerbations while on treatment; change in trough FEV1 at weeks 4, 16, 28, 40, and 52; and change in St George’s Respiratory Questionnaire (SGRQ) total score and percentage of SGRQ responders at weeks 4, 28, and 52. Safety endpoints included incidences of adverse events.
Among 10,355 patients, 3587 (35%; mean age, 65.3 years; 66% male) currently smoked. A history of at least 2 moderate/severe exacerbations within the previous 12 months was reported by 54% (n=1928) of those who currently smoked and by 55% (n=3727) of those who formerly smoked.
The annual rate of on-treatment moderate/severe COPD exacerbations in those who currently and formerly smoked was significantly lower with FF/UMEC/VI vs FF/VI and UMEV/VI. In those who currently smoked, the reduction in the annual exacerbation rate was 15% (95% CI, 5%-23%) for FF/UMEC/VI vs FF/VI and 14% (95% CI, 2%-24%) for FF/UMEC/VI vs UMEC/VI, with corresponding values for those who no longer smoked of 15% (95% CI, 9%-22%) and 30% (95% CI, 23%-36%), respectively.
In those who formerly smoked, the risk of a moderate/severe COPD exacerbation was significantly lower for triple therapy compared with dual therapy (P <.001). For those who currently smoked, the risk was significantly lower with triple therapy compared with FF/VI (P < .001), and the point estimate was favorable for FF/UMEC/VI vs UMEC/VI but not statistically significant (P =.135).
The mean improvement from baseline in trough FEV1 for those who currently and formerly smoked was significantly greater with FF/UMEC/VI vs FF/VI and UMEC/VI at all time points. Among those who formerly smoked, the difference in improvement for all time points with FF/UMEC/VI vs UMEC/VI was 58 to 61 mL, and in those who currently smoked it was 40 to 50 mL.
Improvements in SGRQ total score at week 52 were significantly increased with FF/UMEC/VI compared with FF/VI regardless of smoking status at baseline, although the improvements with FF/UMEC/VI vs UMEC/VI were statistically significance only among those who formerly smoked. The proportion of responders according to SGRQ total score was greater for FF/UMEC/VI vs FF/VI and UMEC/VI for all time points in those who currently and formerly smoked.
Those who formerly smoked had a greater proportion of pneumonia events and exposure-adjusted rates of pneumonia per 1000 patient-years compared with those who currently smoked in all treatment groups, with the greatest differences occurring in the inhaled corticosteroid treatment groups (8.4%, 107.3 per 1000 patient-years vs 6.3%, 74.3 per 1000 patient-years in FF/UMEC/VI; 7.7%, 103.5 per 1000 patient-years vs 5.8%, 83.4 per 1,000 patient-years in FF/VI; and 4.7%, 63.0 per 1000 patient-years vs 4.7%, 58.0 per 1,000 patient-years in UMEC/VI, respectively).
Cardiovascular effects were the most common on-treatment adverse events of special interest, with a similar incidence and rate across all treatment groups for those who currently smoked and those who formerly smoked (10%-11% and 155.0-169.1 per 1000 patient-years, respectively).
The researchers noted that their study was not powered to analyze endpoints by smoking status, which was measured at screening with self-reporting. Also, formal statistical comparisons between those who currently and formerly smoked were not performed as these differences may confound the results of any formal comparison between the groups.
“These findings emphasize the importance of smoking cessation in the moderate-to-severe COPD population, to enable optimal response to treatment,” stated the investigators.
Disclosure: This work was funded by GSK. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Bardsley S, Criner GJ, Halpin DMG, et al. Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis. Respir Med. Published online November 11, 2022. doi:10.1016/j.rmed.2022.107040