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Tiotropium/Olodaterol: A Review in COPD

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Abstract

Tiotropium/olodaterol (Stiolto™ Respimat®, Spiolto™ Respimat®) is a fixed-dose combination of the long-acting antimuscarinic agent tiotropium bromide (hereafter referred to as tiotropium) and the long-acting β2-adrenoreceptor agonist olodaterol delivered via the Respimat® Soft Mist™ inhaler. It is indicated for the maintenance treatment of airflow obstruction in adults with COPD. Several randomized, phase III studies of 6–52 weeks’ duration evaluated the efficacy of once-daily tiotropium/olodaterol in patients with GOLD stage 2–3 or 2–4 COPD. Tiotropium/olodaterol maintenance therapy improved lung function to a greater extent than the individual components or placebo and provided clinically meaningful improvements in health-related quality of life and dyspnoea in 12- and 52-week studies. Tiotropium/olodaterol consistently improved 24-h lung function in 6-week studies, providing greater benefits than the monotherapies, placebo or twice-daily fixed-dose fluticasone propionate/salmeterol. Inspiratory capacity and exercise endurance were also improved with tiotropium/olodaterol following 6 or 12 weeks’ treatment. The tolerability profile of tiotropium/olodaterol in the phase III studies was generally similar to that of the component monotherapies. The most common adverse events and serious adverse events during 52 weeks’ therapy were respiratory in nature, with COPD exacerbation, unsurprisingly, reported most frequently with tiotropium/olodaterol and component monotherapies. Although additional data assessing the effect of tiotropium/olodaterol on exacerbations and comparative studies with other recommended therapies are needed to definitively position tiotropium/olodaterol, current evidence indicates that tiotropium/olodaterol is a useful treatment option for patients with COPD.

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References

  1. World Health Organization. Chronic respiratory diseases: chronic obstructive pulmonary disease. 2015. http://www.who.int/respiratory/copd/en/. Accessed 30 Nov 2015.

  2. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of COPD. 2015. http://www.goldcopd.org/. Accessed 30 Nov 2015.

  3. Tashkin DP, Ferguson GT. Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease. Respir Res. 2013;14:49.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Boehringer Ingelheim Pharmaceuticals. Stiolto™ Respimat® (tiotropium bromide and olodaterol): US prescribing Information. 2015. http://www.fda.gov/. Accessed 30 Nov 2015.

  5. European Medicines Agency. Spiolto Respimat (tiotropium bromide and olodaterol): summary of product characteristics. 2015. http://mri.medagencies.org/Human/Product/Details/44258. Accessed 30 Nov 2015.

  6. Ingelheim Boehringer. Spiolto Respimat 28 puffs: Japanese prescribing information. Tokyo: Nippon Boehringer Ingelheim Co., Ltd.; 2015.

    Google Scholar 

  7. Keating GM. Tiotropium Respimat® Soft Mist™ inhaler: a review of its use in chronic obstructive pulmonary disease. Drugs. 2014;74(15):1801–16.

    Article  PubMed  CAS  Google Scholar 

  8. Deeks ED. Olodaterol: a review of its use in chronic obstructive pulmonary disease. Drugs. 2015;75(6):665–73.

    Article  PubMed  CAS  Google Scholar 

  9. European Medicines Agency. Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution (tiotropium and olodaterol): public assessment report scientific discussion. 2015. http://mri.medagencies.org/Human/Product/Details/44258. Accessed 30 Nov 2015.

  10. Disse B, Reichl R, Speck G, et al. Ba 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci. 1993;52(5–6):537–44.

    Article  PubMed  CAS  Google Scholar 

  11. Belmonte KE. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):297–304.

    Article  PubMed  CAS  Google Scholar 

  12. Tautermann CS, Kiechle T, Seeliger D, et al. Molecular basis for the long duration of action and kinetic selectivity of tiotropium for the muscarinic M3 receptor. J Med Chem. 2013;56(21):8746–56.

    Article  PubMed  CAS  Google Scholar 

  13. Sykes DA, Dowling MR, Leighton-Davies J, et al. The influence of receptor kinetics on the onset and duration of action and the therapeutic index of NVA237 and tiotropium. J Pharmacol Exp Ther. 2012;343(2):520–8.

    Article  PubMed  CAS  Google Scholar 

  14. Haddad EB, Mak JC, Barnes PJ. Characterization of [3H]Ba 679 BR, a slowly dissociating muscarinic antagonist, in human lung: radioligand binding and autoradiographic mapping. Mol Pharmacol. 1994;45(5):899–907.

    PubMed  CAS  Google Scholar 

  15. Takahashi T, Belvisi MG, Patel H, et al. Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. Am J Respir Crit Care Med. 1994;150(6 Pt 1):1640–5.

    Article  PubMed  CAS  Google Scholar 

  16. Cazzola M, Molimard M. The scientific rationale for combining long-acting β2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther. 2010;23(4):257–67.

    Article  PubMed  CAS  Google Scholar 

  17. Maesen FP, Smeets JJ, Costongs MA, et al. Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose-escalation study in COPD. Eur Respir J. 1993;6(7):1031–6.

    PubMed  CAS  Google Scholar 

  18. Maesen FP, Smeets JJ, Sledsens TJ, et al. Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Dutch Study Group. Eur Respir J. 1995;8(9):1506–13.

    PubMed  CAS  Google Scholar 

  19. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19(2):217–24.

    Article  PubMed  CAS  Google Scholar 

  20. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54.

    Article  PubMed  CAS  Google Scholar 

  21. Bouyssou T, Casarosa P, Naline E, et al. Pharmacological characterization of olodaterol, a novel inhaled β2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther. 2010;334(1):53–62.

    Article  PubMed  CAS  Google Scholar 

  22. Casarosa P, Kollak I, Kiechle T, et al. Functional and biochemical rationales for the 24-hour-long duration of action of olodaterol. J Pharmacol Exp Ther. 2011;337(3):600–9.

    Article  PubMed  CAS  Google Scholar 

  23. Ferguson GT, Feldman GJ, Hofbauer P, et al. Efficacy and safety of olodaterol once daily delivered via Respimat in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014;9:629–45.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Koch A, Pizzichini E, Hamilton A, et al. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014;9:697–714.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Troost J, Pivovarova A, Kunz C, et al. Evaluation of the effects of the long-acting β2-agonist olodaterol on the QT and QTc interval in healthy subjects [abstract no. B24]. Am J Respir Crit Care Med. 2013;187(Meeting abstracts):A2603.

  26. Smit M, Zuidhof A, Bos S, et al. Effects of olodaterol and tiotropium on lipopolysaccharide-induced airway hyperresponsiveness and inflammation [abstract no. A60]. Am J Respir Care Med. 2013;187(Meeting abstracts):A1955.

  27. Bouyssou T, Schnapp A, Casarosa P, et al. Addition of the new once-daily LABA BI 1744 to tiotropium results in superior bronchoprotection in pre-clinical models [abstract no. C41]. Am J Respir Crit Care Med. 2010;181(Meeting abstracts):A4445.

  28. Profita M, Bonanno A, Montalbano AM, et al. β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD. Biochim Biophys Acta. 2012;1822(7):1079–89.

    Article  PubMed  CAS  Google Scholar 

  29. Maltais F, Beck E, Webster D, et al. Four weeks once daily treatment with tiotropium+olodaterol (BI 1744) fixed dose combination compared with tiotropium in COPD patients [abstract no. 5557]. In: European Respiratory Society Annual Conference. 2010.

  30. Aalbers R, Maleki-Yazdi MR, Hamilton A, et al. Randomized, double-blind, dose-finding study for tiotropium when added to olodaterol, administered via the Respimat® Inhaler in patients with chronic obstructive pulmonary disease. Adv Ther. 2015;32(9):809–22.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Hohlfeld JM, Sharma A, van Noord JA, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–14.

    Article  PubMed  CAS  Google Scholar 

  32. Buhl R, Maltais F, Abrahams R, et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4). Eur Respir J. 2015;45(4):969–79.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Beeh KM, Westerman J, Kirsten AM, et al. The 24-h lung-function profile of once-daily tiotropium and olodaterol fixed-dose combination in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2015;32:53–9.

    Article  PubMed  CAS  Google Scholar 

  34. Singh D, Ferguson GT, Bolischeck J. Tiotropium+olodaterol shows clinically meaningful improvements in quality of life. Respir Med. 2015;109(10):1312–9.

    Article  PubMed  Google Scholar 

  35. Beeh KM, Derom E, Echave-Sustaeta, et al. ENERGITO: efficacy and safety of once-daily combined tiotropium + olodaterol versus twice-daily combined fluticasone propionate + salmeterol [abstract no. PA4366]. In: European Respiratory Society Annual Congress. 2015.

  36. O’Donnell D, Casaburi R, De Sousa D, et al. Effects of 6 weeks’ treatment with once-daily tiotropium and olodaterol fixed-dose combination on inspiratory capacity and exercise endurance in patients with COPD: the MORACTO™ studies [abstract no. P609]. Am J Respir Crit Care Med. 2015;191(Meeting abstracts):A3972.

  37. Maltais F, Galdiz Iturri JB, Kirsten A, et al. Effects of 12 weeks of once-daily tiotropium and olodaterol fixed-dose combination on exercise endurance in patients with COPD [abstract no. P250]. Thorax. 2014;69(Suppl 2):A186–7.

    Article  Google Scholar 

  38. Ferguson GT, Flezar M, Korn S, et al. Efficacy of tiotropium + olodaterol in patients with chronic obstructive pulmonary disease by initial disease severity and treatment intensity: a post hoc analysis. Adv Ther. 2015;32(6):523–36.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Derom E, Korn S, Hamilton A, et al. Efficacy of tiotropium and olodaterol fixed-dose combination in patients with COPD on β-blockers [abstract no. PA995 plus poster]. In: European Respiratory Society International Annual Congress. 2015.

  40. Ichinose M, Takizawa A, Hamilton A, et al. Efficacy and safety of tiotropium and olodaterol fixed-dose combination via the Respimat® in COPD patients: Japanese subgroup analysis [abstract no. 120]. In: Congress of Asia Pacific Society of Respirology. 2015.

  41. Bai C, Buhl R, Lee SH, et al. Lung function with tioitropium plus olodaterol in East Asian patients with chronic obstructive pulmonary disease [abstract no. 701]. In: Congress of Asia Pacific Society of Respirology. 2015.

  42. Jones PW, Beeh KM, Chapman KR, et al. Minimal clinically important differences in pharmacological trials. Am J Respir Crit Care Med. 2014;189(3):250–5.

    Article  PubMed  Google Scholar 

  43. Buhl R, Tetzlaff K, Korducki L, et al. Pooled safety analysis of adjudicated serious adverse events with the fixed-dose combination of tiotropium + olodaterol [abstract no. P523]. Am J Respir Crit Care Med. 2015;191(Meeting abstracts):A5756.

  44. Bai C, Buhl R, Lee SH, et al. Safety of once-daily tiotropium olodaterl via Respimat in East Asian patients with chronic obstructive pulmonary disease [abstract no. 748]. In: Congress of Asia Pacific Society of Respirology. 2015.

  45. Singh D. New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives. Br J Clin Pharmacol. 2015;79(5):695–708.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

During the peer review process, the manufacturer of tiotropium/olodaterol was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Sohita Dhillon

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  1. Sohita Dhillon
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Correspondence to Sohita Dhillon.

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The preparation of this review was not supported by any external funding.

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Sohita Dhillon is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: S. A. Antoniu, University of Medicine and Pharmacy, Grigore T. Popa, Iasi, Romania; E. Derom, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; A. F. Gelb, Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood (CA), USA; C. Incorvaia, Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy; A. Rossi, Cardiovascular and Thoracic Department, Verona University and General Hospital, Verona, Italy.

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Dhillon, S. Tiotropium/Olodaterol: A Review in COPD. Drugs 76, 135–146 (2016). https://doi.org/10.1007/s40265-015-0527-2

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