Recent Revelations and Advances in Treatment of COPD – the TORCH Study

Prior to the TORCH (Towards a Revolution in COPD Health) study, only smoking cessation and long term oxygen therapy have shown survival benefits in patients with COPD. Although inhaled corticosteroids (ICS) have been used in many patients to help improve symptoms and decrease exacerbations, there has been a lack of long-term studies supporting the ongoing use of these agents.

The TORCH study is a recent, randomised, double blinded and placebo controlled study involving a large number of COPD patients. The primary aim of the study was to determine the impact of the salmeterol / fluticasone propionate combination (Seretide / SFC) against placebo on overall patient mortality. Other objectives included: morbidity related to the rate of COPD exacerbations and health status, mortality and exacerbation end points, requirements for long term oxygen therapy and lung function. After three years of treatment, Seretide was associated with a significant decrease in all cause mortality and improvements in a multitude of morbidities associated with COPD, especially in health related quality of life (QOL).Introduction COPD is fast becoming an important public health problem, forecasted to become the third most common cause of death, behind ischaemic heart disease and cardiovascular disease. Key objectives in optimal management of COPD involve both a decrease in mortality, accompanied by improved morbidity. In addition to smoking cessation and oxygen therapy, recent findings have suggested that ICS and/or long acting beta agonists achieve these goals. ICS have traditionally been used in treatment of COPD based on the hypothesis that these agents suppress inflammatory responses unique to the disease process. Study Design The TORCH study is a prospective, three year, multi-centre, randomised, double blinded, parallel group and placebo controlled study involving approximately 6200 patients with moderate-severe COPD. One of the largest studies of its kind, patients were randomly assigned to treatment with either Seretide, fluticasone propionate, salmeterol or placebo and followed over a three year period. To reduce factors likely to influence results of the study, all long acting bronchodilators / corticosteroids were stopped greater than two weeks prior to the study.Primary Endpoint The primary endpoint of the study was the effect of Seretide on all cause mortality after three years of treatment, compared to placebo. Results from the TORCH study showed that treatment with Seretide produced a relative risk reduction (RRR) in all cause mortality of 17.5% (p=0.052) at three years, compared to placebo and an absolute risk reduction (ARR) of 2.6%.Secondary Endpoints

• Frequency of exacerbations – Patients on Seretide experienced a 25% reduction in moderate and severe exacerbations of COPD each year, compared to placebo (p<0.001). There was also a significant reduction in exacerbations seen in patients on Seretide compared to salmeterol and fluticasone alone.
• Health related quality of life – All study patients experienced an initial improvement in QOL followed by steady deterioration over time. Those on Seretide had the advantage of maintaining an improved QOL for longer and remained above their baseline levels throughout the trial.
• Lung function – Patients treated with placebo demonstrated a decline in lung function of about 50mls / year. On Seretide, an initial improvement in lung function was seen, which was sustained over the next three years. Seretide treated patients evidently displayed a better lung function than placebo, at the end of the study period (p<0.001).

Side EffectsSafety analysis of data from the TORCH study showed that all treatment regimes were well tolerated, with only an increased risk of lower respiratory tract infections (particularly pneumonias) being of concern. However, the reliability of the reporting methods used (patients reporting their own symptoms) was questionable and further studies need to be performed to confirm this finding. Conclusion / Future DirectionsThe TORCH study has revealed favourable results regarding their primary and secondary endpoints in COPD patients. There is a clinically significant reduction in mortality with Seretide. This is achieved with minimal side effects and accompanied by improvements in morbidity and QOL. Further studies need to be conducted to examine the potential increase in lower respiratory tract infections associated with Seretide treatment. Overall, data from this study are very promising, providing much information regarding ICS use in COPD patients and addressing important individual lifestyle factors that should not be forgotten about when treating these patients.References

1. TSANZ symposium presentation: TORCH study shows quality of life and survival for COPD patients, Thoracic Society of Australia and New Zealand 2007 Annual Scientific Meeting, Auckland, New Zealand.
2. Calverley PMA, Anderson JA, Celli B, et al. for the TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. NEJM 2007; 356(8): 775-789
3. Jones PW, Calverley PMA, Celli B et al. The Towards a Revolution in COPD Health (TORCH) study: fluticasone propionate/salmeterol improves and sustains health status in COPD over 3 years. Chest 2006; 130(4 suppl): 177S-178S.