Background: Fibrinogen is the frst qualifed prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated futicasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacer‑ bations. This analysis used IMPACT trial data to examine the relationship between fbrinogen levels and exacerbation outcomes in patients with COPD.
Methods: 8094 patients with a fbrinogen assessment at Week 16 were included, baseline fbrinogen data were not measured. Post hoc analyses were performed by fbrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs).
Results: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile.
Conclusions: Rate and risk of exacerbations was higher in patients with higher fbrinogen levels. This supports the validity of fbrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fbrinogen as an enrichment strategy in trials examining exacerbation outcomes.
Digital Object Identifier (DOI)
This study was funded by GSK (study number CTT116855). The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data and the final responsibility to submit for publication. Ellipta is owned by or licensed to the GSK group of companies.
Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.
Singh, Dave; Criner, Gerard J.; Dransfield, Mark T.; Halpin, David M. G.; Han, MeiLan K.; Lange, Peter; Lettis, Sally; Lipson, David A.; Mannino, David M.; Martin, Neil; Martinez, Fernando J.; Miller, Bruce E.; Wise, Robert; Zhu, Chang-Qing; and Lomas, David, "InforMing the PAthway of COPD Treatment (IMPACT) Trial: Fibrinogen Levels Predict Risk of Moderate or Severe Exacerbations" (2021). Preventive Medicine and Environmental Health Faculty Publications. 52.
Additional file 1: Table 1. Baseline characteristics and demographics by treatment and Week 16 fibrinogen quartile. Table 2. Baseline characteristics and demographics by treatment and Week 16 fibrinogen 3.5 g/L threshold. Table 3. COPD exacerbation history by treatment group and by withdrawal status at Week 16 (ITT population). Table 4. Analysis of fibrinogen levels at Week 16 by treatment group. Table 5. Incidence and rates of AESIs by fibrinogen quartile. Figure 1. Rate of on-treatment moderate/severe exacerbations from Week 16 by continuous fibrinogen level at Week 16; (A) moderate exacerbations; (B) moderate/severe exacerbations; (C) severe exacerbations. Figure 2. Time-to-first on-treatment COPD exacerbation from Week 16 by Week 16 fibrinogen 3.5 g/L threshold: (A) moderate exacerbations; (B) moderate/severe exacerbations; (C) severe exacerbations.