Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials. Academic Article uri icon

Overview

abstract

  • RATIONALE: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted. OBJECTIVES: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast. METHODS: Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year. MEASUREMENTS AND MAIN RESULTS: In the overall intention-to-treat population (n = 4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80-0.97; P = 0.0086) and severe exacerbations by 16.1% (0.84; 0.71-0.99; P = 0.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63-0.88; P = 0.0005); had more than two exacerbations in the prior year (0.79; 0.65-0.96; P = 0.0160); or had baseline eosinophils ≥150 cells/μl (0.81; 0.71-0.93; P = 0.0020), ≥150 to <300 cells/μl (0.84; 0.71-0.98; P = 0.0282), or ≥300 cells/μl (0.77; 0.61-0.97; P = 0.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at ≥150 cells/μl (0.65; 0.52-0.82; P = 0.0003) and 42.7% at ≥300 cells/μl (0.57; 0.37-0.88; P = 0.0111) versus placebo. CONCLUSIONS: This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (≥150 cells/μl, ≥150 to <300 cells/μl, or ≥300 cells/μl) baseline blood eosinophil count.

authors

  • Martinez, Fernando J
  • Rabe, Klaus F
  • Calverley, Peter M A
  • Fabbri, Leonardo M
  • Sethi, Sanjay
  • Pizzichini, Emilio
  • McIvor, Andrew
  • Anzueto, Antonio
  • Alagappan, Vijay K T
  • Siddiqui, Shahid
  • Reisner, Colin
  • Zetterstrand, Sofia
  • Román, Jonas
  • Purkayastha, Debasree
  • Bagul, Nitin
  • Rennard, Stephen I

publication date

  • November 15, 2018

Research

keywords

  • Aminopyridines
  • Benzamides
  • Pulmonary Disease, Chronic Obstructive

Identity

Scopus Document Identifier

  • 85055005656

Digital Object Identifier (DOI)

  • 10.1164/rccm.201712-2493OC

PubMed ID

  • 29763572

Additional Document Info

volume

  • 198

issue

  • 10