Efficacy and safety of tiotropium in COPD patients in primary care--the SPiRiva Usual CarE (SPRUCE) study

Daryl Freeman, Angela Lee, David Price, Daryl Freeman, Angela Lee, David Price

Abstract

Background: Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication. In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.

Methods: This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 mug via the HandiHaler in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]). Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting beta-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment). Treatment effects were determined using non-parametric analysis.

Results: At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102). The improvement was consistent across baseline treatment and COPD severity. Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001). The percentage of patients with > or =1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity. Rescue medication usage was significantly reduced in the tiotropium group compared with placebo. Adverse event profile was consistent with previous studies.

Conclusion: Tiotropium provides additional benefits to usual primary care management in a representative COPD population.

Trial registration: The identifier is: NCT00274079.

Figures

Figure 1
Figure 1
Study flow.
Figure 2
Figure 2
Median changes from baseline in weekly mean number of occasions per day of rescue SABA use over 12 weeks (FAS-DIARY).

References

    1. British Thoracic Society BTS guidelines for the management of chronic obstructive pulmonary disease. The COPD Guidelines Group of the Standards of Care Committee of the BTS. Thorax. 1997;52(suppl 5):S1–S28.
    1. Chronic Obstructive Pulmonary Disease Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care. NICE Clinical Guideline. 2004;12:1–53.
    1. Global Initiative for Chronic Obstructive Pulmonary Disease Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD-Global initiative for chronic obstructive lung disease. 2003. pp. 1–30.
    1. Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, Yernault JC, Decramer M, Higenbottam T, Postma DS, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD): ERS consensus statement. Eur Respir J. 1995;8:1398–420. doi: 10.1183/09031936.95.08081398.
    1. Voelkel NF. Raising awareness of COPD in primary care. Chest. 2000;117(Suppl):372–375. doi: 10.1378/chest.117.5_suppl_2.372S.
    1. van Schayck CP, Chavannes NH. Detection of asthma and chronic obstructive pulmonary disease in primary care. Eur Respir J. 2003;39(Suppl):16–22. doi: 10.1183/09031936.03.00040403.
    1. Freeman D, Nordyke RJ, Isonaka S, Nonikov DV, Maroni JM, Price D, Halbert RJ. Questions for COPD diagnostic screening in primary care setting. Respir Med. 2005;99:1311–1318. doi: 10.1016/j.rmed.2005.02.037.
    1. Gross NJ, Skorodin MS. Role of parasympathetic system in airway obstruction due to emphysema. N Engl J Med. 1984;311:421–425.
    1. Towse LJ, Barnes PJ. Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1996;154:876–880.
    1. Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O'Connor B. Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56:853–859. doi: 10.1016/0024-3205(95)00020-7.
    1. Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack RL, Menjoge SS, Serby CW, Witek T., Jr A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19:217–224. doi: 10.1183/09031936.02.00269802.
    1. Vincken W, van Noord JA, Greefhorst APM, Bantje TA, Kesten S, Korducki L, Cornelissen PJ, Dutch/Belgian Tiotropium Study Group Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Eur Respir J. 2002;19:209–216. doi: 10.1183/09031936.02.00238702.
    1. Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek TJ, Jr, Kesten S, Towse L. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002;122:47–55. doi: 10.1378/chest.122.1.47.
    1. Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. 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. doi: 10.1136/thorax.58.5.399.
    1. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Work Group on Standardization of Respiratory Function Tests. European Community for Coal and Steel. Official position of the European Respiratory Society [Article in French] Rev Mal Respir. 1994;11(Suppl 3):5–40.
    1. American Thoracic Society Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995;152:1107–1136.
    1. McGravin CR, Artvinli M, Naoe H. Dyspnoea, disability, and distance walked: comparison of exercise performance in respiratory disease. Brit Med J. 1978;2:241–243.
    1. Adams SG, Anzueto A, Briggs DD, Jr, Menjoge SS, Kesten S. Tiotropium in COPD patients not previously receiving maintenance respiratory medications. Respir Med. 2006;100:1495–1503. doi: 10.1016/j.rmed.2006.03.034.
    1. Beeh KM, Beier J, Buhl R, Stark-Lorenzen P, Gerken F, Metzdorf N, für die ATEM-Studiengruppe Efficacy of tiotropium bromide (Spiriva®) in patients with chronic obstructive pulmonary disease (COPD) of different severities [Article in German] Pneumologie. 2006;60:341–346. doi: 10.1055/s-2005-919145.
    1. O'Donnell DE, Flüge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, Make B, Magnussen H. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23:832–840.
    1. Celli B, ZuWallack R, Wang S, Kesten S. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest. 2003;124:1743–1748. doi: 10.1378/chest.124.5.1743.
    1. Cazzola M, Di Marco F, Santus P, Boveri B, Verga M, Matera MG, Centanni S. The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther. 2004;17:35–39. doi: 10.1016/j.pupt.2003.09.001.
    1. van Noord JA, Aumann JL, Janssens E, Smeets JJ, Verhaert J, Disse B, Mueller A, Cornelissen PJ. Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD. Eur Respir J. 2005;26:214–222. doi: 10.1183/09031936.05.00140404.
    1. Cazzola M, Centanni S, Santus P, Verga M, Mondoni M, di Marco F, Matera MG. The functional impact of adding salmeterol and tiotropium in patients with stable COPD. Respir Med. 2004;98:1214–1221. doi: 10.1016/j.rmed.2004.05.003.
    1. Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, Balter M, O'donnell D, McIvor A, Sharma S, Bishop G, Anthony J, Cowie R, Field S, Hirsch A, Hernandez P, Rivington R, Road J, Hoffstein V, Hodder R, Marciniuk D, McCormack D, Fox G, Cox G, Prins HB, Ford G, Bleskie D, Doucette S, Mayers I, Chapman K, Zamel N, Fitzgerald M, for the Canadian Thoracic Society/Canadian Respiratory Clinical Research Consortium Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease. Ann Intern Med. 2007
    1. Friedman M, Menjoge S, Anton S, Kesten S. Healthcare costs with tiotropium plus usual care versus usual care alone following 1 year of treatment in patients with chronic obstructive pulmonary disorder (COPD) Pharmacoeconomics. 2004;22:741–749. doi: 10.2165/00019053-200422110-00004.
    1. Oostenbrink JB, Rutten van Mölken MPMH, Al MJ, van Noord JA, Vincken W. One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulmonary disease. Eur Respir J. 2004;23:241–249. doi: 10.1183/09031936.03.00083703.
    1. Pauwels R, Calverley P, Buist AS, Rennard S, Fukuchi Y, Stahl E, Lofdahl CG. COPD exacerbations: the importance of a standard definition. Respir Med. 2004;98:99–107. doi: 10.1016/j.rmed.2003.09.001.
    1. Vestbo J. What is an exacerbation of COPD? Eur Respir Rev. 2004;13:6–13.
    1. Eakin EG, Sassi-Dambron DE, Ries AL, Kaplan RM. Reliability and validity of dyspnea measures in patients with obstructive lung disease. Int J Behav Med. 1995;2:118–134. doi: 10.1207/s15327558ijbm0202_3.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir