Possible Value in Using Clinically Important Deterioration as COPD Prognosis Indicator

A post hoc analysis of the IMPACT trial revealed that optimizing treatment to prevent a clinically important deterioration (CID) could reduce exacerbation risk and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD).

The analysis, published in ERJ Open Research, also concluded that a triple therapy regimen consisting of fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) was better at reducing CID risk than dual therapies consisting of FF/VI or UMEC/VI. These findings suggest that the triple therapy regimen could improve long-term prognosis in patients with COPD with an exacerbation history.

“This current analysis confirms previous evidence that lung function, health status, or exacerbation deteriorations are not concordant events in patients with COPD. Consequently, individual CID events likely measure different forms of deterioration and sustained suboptimal responses, highlighting the heterogeneity of multiple types of worsening that occur over relatively short time periods in COPD,” wrote the investigators.

CID is a multicomponent measurement of disease worsening in patients with COPD that examines suboptimal responses to treatment and disease instability. Previous studies have shown CID to be associated with mortality and morbidity risks. However, data on patients with COPD who are at a high risk for exacerbations need to be assessed to fully understand how CID affects those risks.

The IMPACT trial was a phase 3, double-blind, parallel group, 52-week, multicenter study evaluating 10,355 patients aged 40 or older with symptomatic COPD and who experienced at least 1 exacerbation during the year prior to the study. Patients were randomized to receive FF/UMEC/VI 100/62.5/25 mcg (n = 4151), FF/VI 100/25 mcg (n = 4134), or UMEC/VI 62.5/25 mcg (n = 2070) once per day using a dry-power inhaler.

The investigators of the analysis used data from the trial to determine the effects of CID on COPD prognosis in a patient population with a history of exacerbations. CID was defined as experiencing moderate to severe exacerbations, deterioration in lung function, or deterioration in health status, which is assessed using scores generated from the COPD Assessment Test (CIDCAT) or the St. George’s Respiratory Questionnaire (CIDSGRQ).

Using the CIDSGRQ definition of health status, patients who were positive for CID at week 28 were found to have a 75% increase in moderate to severe exacerbations annually (rate ratio [RR], 1.75; 95% CI, 1.60-1.92; P < .001) and a 96% increase in severe exacerbation rate (RR, 1.96; 95% CI, 1.56-2.47; P < .001) during weeks 29 to 52 compared with CID-negative patients.

CID-negative patients also saw a greater improvement in lung function and health status as determined by the SGRQ at week 52 compared with CID-positive patients (P < .001).

Similar results were observed when incorporating the CIDCAT definition, finding that at week 28, CID-positive patients had a 72% increased risk in moderate to severe exacerbations (RR, 1.72; 95% CI, 1.56.1.89; P < .001) and a 91% increased risk in severe exacerbations (RR, 1.91; 95% CI, 1.50-2.42; P < .001) over weeks 29 to 52 compared with CID-negative patients.

During the survival analysis, mortality risks increased by 55% (P = .069) and 80% (P = .025) for CID-positive patients using the CIDSGRQ definition and the CIDCAT definition, respectively, by week 28.

When comparing treatment arms using the CIDSGRQ definition, triple therapy significantly reduced the risk of CID by 33% by week 28 and 31% by week 52 vs FF/VI (P <.001). Additionally, triple therapy carried a 26% and 24% reduced risk at week 28 and week 52, respectively, compared with UMEC/VI (P <.001).

This was similar when the investigators used the CIDCAT definition, finding that triple therapy vs FF/VI garnered a 28% reduced CID risk at week 28 and a 27% reduced risk at week 52. In addition, compared with UMEC/VI, there were reduced risks of 23% and 22% (P < .001) at weeks 28 and 52, respectively .

The investigators identified the relatively short 5-month follow-up period and a focus on patients with a history of exacerbations, as opposed to the general COPD population, as study limitations.

“Despite these limitations, given the broad range of benefits seen with FF/UMEC/VI compared with UMEC/VI in IMPACT, further studies may be warranted to examine the benefits of add-on [inhaled corticosteroids] in preventing CID in patients with less advanced disease,” concluded the investigators.

Reference

Han MK, Criner GJ, Dransfield MT, et al. Prognostic value of clinically important deterioration in COPD: IMPACT trial analysis. ERJ Open Res. Published online March 8, 2021. Accessed March 17, 2021. doi: 10.1183/23120541.00663-2020