Predicting COPD Exacerbations, Treatment Responses via Eosinophil Counts

Clinicians may be able to predict the exacerbation risk and response to inhaled corticosteroids (ICS) in individuals with chronic obstructive pulmonary disease (COPD) treated with formoterol through their blood eosinophil count, according to a study published by the Lancet.

Researchers identified 4528 individuals with COPD, a history of exacerbations, and recorded blood eosinophil counts from 3 randomized, double-blinded, double-dummy, parallel-group, multicenter controlled trials (ClinicalTrials.gov identifiers: NCT00206167, NCT00206154, and NCT00419744) treated with budesonide/formoterol and retrospectively analyzed the data to determine whether eosinophil counts had predictive value in determining the exacerbation risk and clinical response to ICS treatment.

In individuals treated with formoterol alone, a relationship between nonlinear increases in exacerbation and eosinophil counts was observed, with individuals with low eosinophil counts starting at 0.5 exacerbations per year and increasing to 1.8 exacerbations per year in individuals with high eosinophil counts (<0.01×10⁹ cells/L and >0.80×10⁹ cells/L, respectively), whereas the rates of exacerbations in individuals being treated with budesonide/formoterol 160/4.5 μG were found to be independent of their eosinophil count.

There was a significant treatment effect noted at an eosinophil count of 0.10×10⁹ cells/L, with a reduction in exacerbations noted in the budesonide/formoterol group compared with formoterol alone (exacerbation rate ratio, 0.75 (95% CI, 0.57-0.99; P_interaction =.015). Data regarding participants’ St George’s Respiratory Questionnaire scores (P_interaction =.0043) and forced expiratory volume in 1 second values (linear effect P <.0001, P_interaction =.067) were found to be more significantly affected by the interaction between eosinophil counts and budesonide/formoterol compared with formoterol alone.

Treatment interactions between neutrophil counts and treatments of budesonide/formoterol were seen at both high and low doses (P_interaction =.00060 and P_interaction =.00012).

Researchers developed a modified short-term risk for COPD (SCOPEX) as an exacerbation risk assessment tool (SCOPEXe) to include the eosinophil count when assessing the risk for an exacerbation within 12 months after treatment with budesonide/formoterol and formoterol alone. The modified SCOPEXe found a reduced risk for individuals treated with budesonide/formoterol compared with formoterol at an exacerbation rate ratio of 0.77 (95% CI, 0.65-0.90).

Only a history of smoking interacted significantly with budesonide/formoterol, serving as an independent predictor of an individual’s response to ICS treatment and reduction in exacerbations (eosinophil count, P_interaction =.013; smoking history, P_interaction =.015). In addition, an individual’s smoking status, eosinophil count, and treatment combined were found to interact significantly (P_interaction =.011).

Clinicians should consider the use of budesonide/formoterol in the treatment of COPD in this patient population, as therapeutic benefits were independent of eosinophil counts. However, clinicians should also keep in mind the increased risk for exacerbations observed in individuals only taking formoterol with increasing eosinophil counts, closely monitor these individuals, and consider changing treatment from long-acting beta-2 agonist alone to ICS-LABA.

Reference

Bafadhel M, Peterson S, De Blas MAD, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomized trials [published online January 10, 2018]. Lancet. doi:10.1016/S2213-2600(18)30006-7