PURPOSE: Salmeterol (SAL) and fluticasone propionate (FP) are well tolerated individually but there are limited data on their long-term use as a single formulation (FSC) in COPD. We evaluated the safety profile of FSC and components in the three year TORCH study.
METHODS: The safety population comprised 6184 COPD patients (mean age 65yrs, 76% males, 44% mean predicted post-bronchodilator FEV1; 3.7% reversibility) who received FP 500mcg (n=1552), SAL 50mcg (n=1542), FSC 500/50 (n=1546) or placebo (n=1544) bid via Diskus(R). Adverse events were monitored, with a focus on bone fractures in the whole population, and bone mineral density (BMD) and ocular changes in a subset of US patients (n=658).
RESULTS: Overall incidence of investigator reported adverse events (rate/1000 treatment years) was similar between groups (placebo 2983; SAL 2767; FP 2965; FSC 2868). The most common event was COPD exacerbations (placebo 920; SAL 757; FP 776; FSC 667). There was no increased HPA axis or cardiac adverse events reported on any treatment. There were more pneumonias reported in steroid containing arms (placebo 39; SAL 42; FP 69; FSC 71) but no difference in the total number of lower respiratory tract infections (LRTI) including exacerbations treated with antibiotics, and no difference between SFC and placebo in deaths due to pneumonia. There was a non-significant increase in probability of bone fracture (6.3% SFC vs 5.1% placebo) however no difference in non-traumatic fractures (1.7% SFC vs 1.8% placebo). In the US subset, adjusted % change in BMD at 3 years (total hip) was −3.1% placebo, −1.7% SAL, −2.9% FP, −3.2% FSC, p>0.05 for all comparisons. No difference in development of cataracts was found between groups during the study.
CONCLUSION: Long-term use of FSC produced minimal side effects. There was an increased reporting rate of pneumonia but not overall LRTIs. The positive outcomes noted in TORCH and these data indicate FSC has a favourable long-term benefit/risk ratio compared with placebo.
CLINICAL IMPLICATIONS: FSC 50/500mcg bid provides an effective and well tolerated treatment for COPD patients.
DISCLOSURE: Gary Ferguson, Grant monies (from industry related sources) This study is funded by a grant from GlaxoSmithKline. Departments of BC, CJ, PC, GF, JV, receive funding from GlaxoSmithKline for specific research projects; Employee JA and JY are employees of GlaxoSmithKline; Consultant fee, speaker bureau, advisory committee, etc. PJ, PC, BC, GF, CJ, JV and NP have been speakers and consultants for companies including GSK, Pfizer, AstraZeneca, Boehringer Ingelheim; Other JV’s wife was until 2004 a GSK employee; Product/procedure/technique that is considered research and is NOT yet approved for any purpose, FSC 500/50 dose currently unlicensed for COPD in U.S.