COPD eosinophil counts predict steroid responders

Triple therapy with an inhaled corticosteroid is particularly helpful for patients with chronic obstructive pulmonary disease (COPD) who have high baseline eosinophil counts, a trial involving more than 10,000 patients found.

Former smokers received greater benefit from inhaled corticosteroids (ICS) than did current smokers, reported lead author Steven Pascoe, MBBS, of GlaxoSmithKline and colleagues. The investigators noted that these findings can help personalize therapy for patients with COPD, which can be challenging to treat because of its heterogeneity. The study was published in Lancet Respiratory Medicine.

The phase 3 IMPACT trial compared single-inhaler fluticasone furoate–umeclidinium–vilanterol with umeclidinium-vilanterol and fluticasone furoate–vilanterol in patients with moderate to very severe COPD at high risk of exacerbation. Of the 10,333 patients involved, approximately one-quarter (26%) had one or more severe exacerbations in the previous year and half (47%) had two or more moderate exacerbations in the same time period. All patients were symptomatic and were aged 40 years or older. A variety of baseline and demographic patient characteristics were recorded, including blood eosinophil count, smoking status, and others. Responses to therapy were measured with trough forced expiratory volume in 1 second (FEV₁), symptom scoring, and a quality of life questionnaire.

After 52 weeks, results showed that higher baseline eosinophil counts were associated with progressively greater benefits in favor of triple therapy. For patients with baseline blood eosinophil counts of at least 310 cells per mcL, triple therapy was associated with about half as many moderate and severe exacerbations as treatment with umeclidinium-vilanterol (rate ratio = 0.56; 95% confidence interval, 0.47-0.66). For patients with less than 90 cells per mcL at baseline, the rate ratio for the same two regimens was 0.88, but with a confidence interval crossing 1 (0.74-1.04). For fluticasone furoate–vilanterol vs. umeclidinium-vilanterol, high baseline eosinophil count again demonstrated its predictive power for ICS efficacy, again with an associated rate ratio of 0.56 (0.47-0.66), compared with 1.09 (0.91-1.29) for patients below the lower threshold. Symptom scoring, quality of life, and FEV₁ followed a similar trend, although the investigators noted that this was “less marked” for FEV₁. Although the trend held regardless of smoking status, benefits were more pronounced among former smokers than current smokers.

“In former smokers, ICS benefits were observed at all blood eosinophil counts when comparing triple therapy with umeclidinium-vilanterol, whereas in current smokers no ICS benefit was observed at lower eosinophil counts, less than approximately 200 eosinophils per [mcL],” the investigators wrote.

“Overall, these results show the potential use of blood eosinophil counts in conjunction with smoking status to predict the magnitude of ICS response within a dual or triple-combination therapy,” the investigators concluded. “Future approaches to the pharmacological management of COPD should move beyond the simple dichotomization of each clinical or biomarker variable, toward more complex algorithms that integrate the interactions between important variables including exacerbation history, smoking status, and blood eosinophil counts.”

The study was funded by GlaxoSmithKline. The investigators disclosed additional relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, and others.

SOURCE: Pascoe S et al. Lancet Resp Med. 2019 Jul 4. doi: 10.1016/S2213-2600(19)30190-0.

Triple therapy with an inhaled corticosteroid is particularly helpful for patients with chronic obstructive pulmonary disease (COPD) who have high baseline eosinophil counts, a trial involving more than 10,000 patients found.

Former smokers received greater benefit from inhaled corticosteroids (ICS) than did current smokers, reported lead author Steven Pascoe, MBBS, of GlaxoSmithKline and colleagues. The investigators noted that these findings can help personalize therapy for patients with COPD, which can be challenging to treat because of its heterogeneity. The study was published in Lancet Respiratory Medicine.

The phase 3 IMPACT trial compared single-inhaler fluticasone furoate–umeclidinium–vilanterol with umeclidinium-vilanterol and fluticasone furoate–vilanterol in patients with moderate to very severe COPD at high risk of exacerbation. Of the 10,333 patients involved, approximately one-quarter (26%) had one or more severe exacerbations in the previous year and half (47%) had two or more moderate exacerbations in the same time period. All patients were symptomatic and were aged 40 years or older. A variety of baseline and demographic patient characteristics were recorded, including blood eosinophil count, smoking status, and others. Responses to therapy were measured with trough forced expiratory volume in 1 second (FEV₁), symptom scoring, and a quality of life questionnaire.

After 52 weeks, results showed that higher baseline eosinophil counts were associated with progressively greater benefits in favor of triple therapy. For patients with baseline blood eosinophil counts of at least 310 cells per mcL, triple therapy was associated with about half as many moderate and severe exacerbations as treatment with umeclidinium-vilanterol (rate ratio = 0.56; 95% confidence interval, 0.47-0.66). For patients with less than 90 cells per mcL at baseline, the rate ratio for the same two regimens was 0.88, but with a confidence interval crossing 1 (0.74-1.04). For fluticasone furoate–vilanterol vs. umeclidinium-vilanterol, high baseline eosinophil count again demonstrated its predictive power for ICS efficacy, again with an associated rate ratio of 0.56 (0.47-0.66), compared with 1.09 (0.91-1.29) for patients below the lower threshold. Symptom scoring, quality of life, and FEV₁ followed a similar trend, although the investigators noted that this was “less marked” for FEV₁. Although the trend held regardless of smoking status, benefits were more pronounced among former smokers than current smokers.

“In former smokers, ICS benefits were observed at all blood eosinophil counts when comparing triple therapy with umeclidinium-vilanterol, whereas in current smokers no ICS benefit was observed at lower eosinophil counts, less than approximately 200 eosinophils per [mcL],” the investigators wrote.

“Overall, these results show the potential use of blood eosinophil counts in conjunction with smoking status to predict the magnitude of ICS response within a dual or triple-combination therapy,” the investigators concluded. “Future approaches to the pharmacological management of COPD should move beyond the simple dichotomization of each clinical or biomarker variable, toward more complex algorithms that integrate the interactions between important variables including exacerbation history, smoking status, and blood eosinophil counts.”

The study was funded by GlaxoSmithKline. The investigators disclosed additional relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, and others.

SOURCE: Pascoe S et al. Lancet Resp Med. 2019 Jul 4. doi: 10.1016/S2213-2600(19)30190-0.

Triple therapy with an inhaled corticosteroid is particularly helpful for patients with chronic obstructive pulmonary disease (COPD) who have high baseline eosinophil counts, a trial involving more than 10,000 patients found.

Former smokers received greater benefit from inhaled corticosteroids (ICS) than did current smokers, reported lead author Steven Pascoe, MBBS, of GlaxoSmithKline and colleagues. The investigators noted that these findings can help personalize therapy for patients with COPD, which can be challenging to treat because of its heterogeneity. The study was published in Lancet Respiratory Medicine.

The phase 3 IMPACT trial compared single-inhaler fluticasone furoate–umeclidinium–vilanterol with umeclidinium-vilanterol and fluticasone furoate–vilanterol in patients with moderate to very severe COPD at high risk of exacerbation. Of the 10,333 patients involved, approximately one-quarter (26%) had one or more severe exacerbations in the previous year and half (47%) had two or more moderate exacerbations in the same time period. All patients were symptomatic and were aged 40 years or older. A variety of baseline and demographic patient characteristics were recorded, including blood eosinophil count, smoking status, and others. Responses to therapy were measured with trough forced expiratory volume in 1 second (FEV₁), symptom scoring, and a quality of life questionnaire.

After 52 weeks, results showed that higher baseline eosinophil counts were associated with progressively greater benefits in favor of triple therapy. For patients with baseline blood eosinophil counts of at least 310 cells per mcL, triple therapy was associated with about half as many moderate and severe exacerbations as treatment with umeclidinium-vilanterol (rate ratio = 0.56; 95% confidence interval, 0.47-0.66). For patients with less than 90 cells per mcL at baseline, the rate ratio for the same two regimens was 0.88, but with a confidence interval crossing 1 (0.74-1.04). For fluticasone furoate–vilanterol vs. umeclidinium-vilanterol, high baseline eosinophil count again demonstrated its predictive power for ICS efficacy, again with an associated rate ratio of 0.56 (0.47-0.66), compared with 1.09 (0.91-1.29) for patients below the lower threshold. Symptom scoring, quality of life, and FEV₁ followed a similar trend, although the investigators noted that this was “less marked” for FEV₁. Although the trend held regardless of smoking status, benefits were more pronounced among former smokers than current smokers.

“In former smokers, ICS benefits were observed at all blood eosinophil counts when comparing triple therapy with umeclidinium-vilanterol, whereas in current smokers no ICS benefit was observed at lower eosinophil counts, less than approximately 200 eosinophils per [mcL],” the investigators wrote.

“Overall, these results show the potential use of blood eosinophil counts in conjunction with smoking status to predict the magnitude of ICS response within a dual or triple-combination therapy,” the investigators concluded. “Future approaches to the pharmacological management of COPD should move beyond the simple dichotomization of each clinical or biomarker variable, toward more complex algorithms that integrate the interactions between important variables including exacerbation history, smoking status, and blood eosinophil counts.”

The study was funded by GlaxoSmithKline. The investigators disclosed additional relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, and others.

SOURCE: Pascoe S et al. Lancet Resp Med. 2019 Jul 4. doi: 10.1016/S2213-2600(19)30190-0.