Tiotropium in the treatment of COPD Walter Vincken, University Hospital Brussels (UZ Brussel) 8 December 2010 Letter to the Editor of BMC Pulmonary Medicine. Tiotropium in the treatment of COPD. I read with interest Neyt et al.’s article published on-line in BMC Pulmonary Medicine on September 15, 2010.(1) In this cost-utility analysis, they question the ‘value for money’ of tiotropium in the treatment of chronic obstructive pulmonary disease (COPD) utilizing Belgian reimbursement regulations ‘under real-world conditions’. However valuable their analysis might seam, in doing so, they only took into consideration the effects of tiotropium on exacerbation- and hospitalization rates, including effects on quality of life (QoL) related to avoiding exacerbations. As already pointed out by Kostikas and Bouros in their commentary in the same issue of your journal (2), such an approach neglects the beneficial effects that patients in the real ‘real-world’ experience day after day for the rest of their lives, i.e. clinically important improvements in dyspnea, exercise tolerance and QoL not linked to exacerbations. Numerous double-blind, randomized clinical trials (RCT) in large patient populations, with a duration from 3 to 12 months comparing tiotropium to placebo (3-15), ipratropium (16) or salmeterol (17,18), are available, showing that tiotropium improves statistically significantly and clinically importantly airway obstruction, hyperinflation, dyspnea, need for rescue-medication, exercise tolerance and/or QoL. Although the UPLIFT trial (3, following up nearly 6000 COPD patients during 4 years (and thereby the largest ever trial in COPD), failed to reveal an effect of tiotropium (inhaled on top of usual treatment) on the decline in FEV1, other important long-term benefits of tiotropium such as a significant reduction in mortality risk was clearly present, a finding denied by Neyt et al.(1) but recently included in the Summary of Product Characteristics of tiotropium. Finally, Neyt et al.’s (1) statement that tiotropium “does not perform much better than its comparator”, i.e. salmeterol, on COPD exacerbations and related hospitalizations is now also to be considered out-dated in view of a large 1-year RCT (19) including over 7000 COPD patients recently presented at the Annual Congress of the European Respiratory Society (admittedly one week after their publication). In this so-called POET trial tiotropium compared to salmeterol significantly delayed the time to first exacerbation (primary endpoint) by 17% (p<0.0001) as well as time to first hospitalization (by 28%; p<0.0001). Tiotropium also significantly reduced the annual rate of exacerbations and exacerbation-related hospitalizations (p<0.002). The POET trial (19) thereby unequivocally confirms the trends observed in previous, smaller and shorter, trials (17, 18). In conclusion, as valuable as it is, Neyt et al.’s (1) work does not take into consideration all scientifically proven and clinically important aspects of undecipherable value in the real-life daily management of COPD patients whose suffering can nowadays clearly be alleviated by long-acting bronchodilators in general and tiotropium in particular. The question is whether and how much society is willing to pay for the benefit of patients with COPD, a disease that only recently is receiving the attention it deserves. Walter Vincken, M.D., Ph.D. Head Respiratory Division, University Hospital Brussels (UZ Brussel), and Professor in respiratory physiology, pathophysiology and pulmonary medicine, Vrije Universiteit Brussel. References: 1. Neyt M, et al. Tiotropium’s cost-effectivenss for the treatment of COPD: a cost-utility analysis under real-world conditions. BMC Pulmonary Medicine 2010, 10:47 doi:10.1186/1471-2466-10-47 2. Kostikas K, Bouros D. “Show me the money”: a fair criticism of economic studies on inhaled bronchodilators for COPD. BMC Pulmonary Medicine 2010, 10:48 doi: 10.1186/1471-2466-10-48 3. Tashkin D, et al. A 4 year trial of tiotropium in COPD (UPLIFT trial) New England Journal of Medicine 2008, 359:1543-1554. 4. Tonnel AB, et al. Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD. International Journal of COPD 2008, 3:301-310. 5. Casaburi R, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive disease. Eur Respir J 2002, 19:217-224. 6. Dusser D, et al. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur Respir J 2006, 27:547-555. 7. Verkindre, et al. The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease. Respiration 2006, 73:420-427. 8. Casaburi R, et al. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilition in patients with COPD. Chest 2005, 127:809-817. 9. Ambrosino N, et al. Tiotropium and exercise training in COPD patients: effect on dyspnea and exercise tolerance. International Journal of COPD 2008, 3(4):771-780. 10. Beeh KM, et al. Wirksamkeit von tiotropiumbromid bei verschiedenen Schweregraden der chronisch-obstructiven lungenerkrankung (COPD). Pneumologie 2006, 60:341-346. 11. Chan CKM, et al. A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease. Can Respir J 2007, 14:465-472. 12. Niewoehner DE, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator. Ann Intern Med 2005, 143:319-326. 13. Freeman D, et al. Efficacy and safety of tiotropium in COPD patients in primary care- the SPRUCE study. Respir Res 2007, 8:45. 14. Johansson G, et al. Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD. Prim Care Respir J 2008, 17:169-175. 15. Moita J, et al. Tiotropium improves FEV1 in patients with COPD irrepsective of smoking status. Pulm Pharmacol Ther 2008, 21:146-151. 16. Vincken W, et al. Improved health outcomes in patients with COPD during 1 year’s treatment with tiotropium. Eur Respir J 2002, 19:209-216. 17. Brusasco V, et al. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax 2003, 58:399-404. 18. Briggs DD, et al. Improved daytime spirometric efficacy of tiotropium compared with salmeterol in patients with COPD. Pulm Pharmacology & Ther 2005, 18:397-404. 19. Vogelmeier C, et al. Reductions in COPD exacerbations with tiotropium compared to salmeterol- the POET-trial. Eur Respir J 2010(suppl):P5091, ERS 2010, Barcelona. Competing interests WV has been a member of advisory boards for Altana/Nycomed, AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline, Meda, MSD, Novartis and UCB; has given lectures for these pharmaceutical companies as well as for Abbott and Zambon; and has received research or educational grants from AstraZeneca, Boehringer Ingelheim/Pfizer, GlaxoSmithKline and Novartis.