The INSPIRE (Investigating New Standards for Prophylaxis In Reduction of Exacerbations) trial demonstrated that while the two study medications; Seretide™ 50/500µgDiskus™ (salmeterol/fluticasone propionate) and tiotropium bromide 18µg Handihaler® had a comparable effect on exacerbation rates, those who received Seretide experienced substantial health status improvements and better survival periods than those who received tiotropium. INSPIRE is the first prospective trial to report a statistically significant difference in the relative risk of all-cause mortality between two recognized for COPD treatments. 1
The study is published in The American Journal of Respiratory and Critical Care Medicine.
INSPIRE study is the first to look at variations in exacerbation rates and related outcomes linked to two frequently used drugs COPD treatment. The primary endpoint of the INSPIRE study was a comparative decrease in exacerbations, an abrupt deterioration of symptoms, which are debilitating and grow as the disease advances.
While the total exacerbations described between the two study groups were not substantially different, overall rates were 1.28 for Seretide and 1.32 for tiotropium bromide (p=0.656), the treatment for the acute exacerbation chosen by investigators whilst blinded was different. Exacerbations that needed antibiotics happened more often among those taking Seretide, while exacerbations that required systemic steroids happen more often among those taking tiotropium – this suggests that the nature of the exacerbations was different and that people are affected in different ways by COPD treatments.
The study also revealed that COPD patients taking Seretide had a 52% lower risk of dying from any cause, compared to those taking tiotropium bromide a statistically significant finding (p=0.012). This lowering of mortality risk was observed by the thirteenth week of treatment and continued to increase as the study progressed. The study also showed that the Seretide patients had significant improvements in quality of life from early in the study compared to patients on tiotropium bromide (2.07 unit improvement at 2 years, p=0.038), as measured by the St George’s Respiratory Questionnaire (SGRQ), a validated instrument used to assess the impact of airway disease on overall health, daily life, and perceived well-being. These benefits lasted through the length of the 104 week study.
“The results seen in INSPIRE showing improvements in quality of life and survival are important for patients with COPD. There is no cure for COPD so we must manage the disease as effectively as possible to provide patients with the best outcomes,” Professor Wisia Wedzicha, Royal Free Hospital, London, said.
Safety and tolerability
The study reported an 8% increase in pneumonias among those taking Seretide, compared to a 4% increase among those receiving tiotropium bromide. 6% of the Seretide group reported candidiasis, compared to 3% in the tiotropium group.
Those receiving tiotropium were 29% more likely to drop out from the study. The probability of withdrawing prior to week 104 was 34.5% on Seretide and 41.7% on tiotropium bromide (p=0.005). The withdrawals were much higher among participants who had worse health status and who deteriorated faster. As more patients drop out of a study it can lead to a ‘health survivor’ effect with less severe patients in one treatment group being compared to more severe patients in the other treatment group.
INSPIRE was a European, 2-year multicentre, randomized, double-blind, double-dummy controlled trial involving 1,300 COPD patients – it compared the effects of Seretide and tiotropium bromide.
“The study raises important questions regarding the nature of this progressive disease. Patients appeared to experience differences in the nature of their exacerbations, with different treatment being prescribed for each group, Seretide patients received more antibiotics during their exacerbations, and tiotropium patients more oral corticosteroid treatments and this resulted in different outcomes for patients. This study therefore could have important implications for the choice of medication used to manage patients with COPD,” Wedzicha concluded.
“The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide”
Jadwiga A. Wedzicha, Peter M. A. Calverley, Terence A. Seemungal, Gerry Hagan, Zainab Ansari and Robert A. Stockley for the INSPIRE Investigators
American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 19-26, (2008) doi: 10.1164/rccm.200707-973OC
Click here to view abstract online
Written by – Christian Nordqvist