Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations

Abstract

Background

Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV₁) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV₁ and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.

Methods

This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV₁ and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2–12. Responders were defined by ≥100 mL improvement in prebronchodilator FEV₁ and ≥4-point decrease in SGRQ total score.

Results

Overall, 2,331 and 1,799 patients were included in the 0–2- and 0–12-month responder analyses, respectively, and 2,360 patients in the 2–12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV₁ responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV₁ (odds ratio, 5.57; 95% confidence interval, 4.14–7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83–5.31). Two-month response in FEV₁ (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.

Conclusion

Early FEV₁ and SGRQ treatment responses relate to their changes at 12 months. FEV₁ response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required.

Keywords:

• anti-inflammatories
• bronchodilator effect
• chronic obstructive pulmonary disease
• predictors
• risk assessment
• risk factors

Acknowledgments

This analysis was funded by AstraZeneca. Anna Mett and Shaun Foley of inScience Communications, Springer Healthcare, provided medical writing assistance, funded by AstraZeneca. The authors thank Malin Fagerås of AstraZeneca R&D, Gothenburg, Sweden, and Thomas Similowski, of Groupe Hospitalier Pitié-Salpêtrière, Paris, France, for their assistance with the development of this manuscript. Anders Persson of AstraZeneca R&D, Gothenburg, Sweden, performed additional statistical analyses.

Disclosure

PMC is a board member for Boehringer Ingelheim, the Department of Health Respiratory Programme Board, GlaxoSmithKline, and Nycomed. He has been a consultant for Novartis and provided expert testimony for Forest. PMC has received honoraria for advising on the conduct and analysis of clinical trial data from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Nycomed. He has also spoken at meetings supported by these companies. Support for travel to meetings has been provided by AstraZeneca.

The University of Groningen has received honoraria for DSP advising on the conduct and analysis of clinical trial data from AstraZeneca, Nycomed, and Teva as well as for lectures at meetings supported by AstraZeneca, Chiesi, GlaxoSmithKline, Nycomed, and Teva. The University of Groningen has received money for research by unrestricted educational grants from AstraZeneca and Chiesi. AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Nycomed have provided support for travel to meetings.

ARA is a consultant and speaker for AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Dey Pharma, GlaxoSmithKline, and Pfizer, and has received honoraria from these companies. Educational presentations have been developed for AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Dey Pharma, and Pfizer. Support for travel to meetings has also been provided by AstraZeneca.

BJM is a board member for AstraZeneca, Boehringer Ingelheim, Dey Pharma, Embryon, Forest, Johnson and Johnson, MedImmune, Novartis, Nycomed, Pfizer, and Respironics, and a consultant for Astellas and Chiesi. Clinical trial data have been reviewed for Spiration, with grants currently pending with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MedImmune, Nabi, Pfizer, and Sunovian. Lectures have been presented on behalf of Boehringer Ingelheim, GlaxoSmithKline, and Pfizer, with video presentations developed for Boehringer Ingelheim and questionnaires produced for Union Chimique Belge. Educational presentations and programs have been developed (Circulate WebMD, Creative Educational Concepts, France Foundation, Johns Hopkins University, Medscape, National Jewish Health, and the Veteran’s Health Administration [VHA]), and BJM has been a speaker for educational programs at Abbott, the American Academy of Family Practice, the American College of Chest Physicians, the American Thoracic Society, Breathe LA, the Cleveland Clinic, and VHA. Support for travel to meetings has also been provided by AstraZeneca.

GE and SP are former employees of AstraZeneca and own stocks within the company.

CRJ is a board member for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Limited, and Novartis, and a consultant for Chiesi and AstraZeneca. Educational presentations have been developed for AstraZeneca and GlaxoSmithKline, with grants also pending for these companies. Lectures have been presented on behalf of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hunter Immunology, and Novartis. Support for travel to meetings has been provided by AstraZeneca. The authors report no other conflicts of interest in this work.