Tools for Practice


#152 Tempered Enthusiasm for Tiotropium in Asthma


CLINICAL QUESTION
Is tiotropium useful as add-on therapy in asthmatic patients who are poorly controlled on an Inhaled Corticosteroid (ICS) or ICS + Long-Acting Beta Agonist (LABA)?

BOTTOM LINE
In moderate-severe asthma, uncontrolled on ICS or ICS+LABA, the addition of Tiotropium prevents exacerbations for one in 18-36 patients over 4-52 weeks. Much of the research is at high risk of bias and changes in other surrogate outcomes (like FEV1) are of uncertain clinical importance.  


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EVIDENCE
  • Systematic review, 13 RCTs (4,966 patients >12 years), asthma, 4-52 weeks duration, 11/13 trials used Respimat® inhaler:1 
    • Tiotropium + ICS versus ICS (moderate asthma): 
      • Improved PEF (22-24 L/min) and FEV1 (140-150 mL). 
      • Reduced number of patients with ≥1 exacerbation [10.5% versus 13.3%, Number Needed to Treat (NNT)=36]. 
    • Tiotropium + ICS + LABA versus ICS + LABA (severe asthma): 
      • Improved PEF (16-20 L/min) and FEV1 (80-120 mL). 
      • Reduced number of patients with ≥1 exacerbation (18.2% versus 24.0%, NNT=18). 
    • No difference in adverse events. 
    • Minimum clinically important difference (MCID) for FEV1 is 230 mL.2 
    • Limitations: 6/13 trials were unpublished manufacturer trials. 
  • Two of the above unpublished trials were subsequently published together.3  
    • 2,103 asthma patients on ICS, randomized to once-daily tiotropium (Respimat® inhaler), twice-daily salmeterol or placebo, 24 weeks: 
      • Both tiotropium and salmeterol had similar statistically significant improvement in FEV1 although neither reached MCID.2  
      • Asthma exacerbations (requiring oral steroids) not well reported, conflicting results. 
      • Limitations: Industry-sponsored, multiple outcomes with selective reporting, no mention of rescue medications or hospitalizations. 
  • Smaller systematic reviews (5-6 RCTs) report that tiotropium added to ICS ± LABA increases PEF and FEV1.4,5 
  Context:   
  • 2015 Global Initiative for Asthma guidelines state tiotropium is an option in patients on medium- to high-dose ICS + LABA in patients ≥18 years.6 
  • Tiotropium is available in two types of inhalers: HandiHaler® (dry powder capsule inhaler) and Respimat® (aqueous solution soft mist inhaler).7 
  • There is controversy regarding the possibility of increased mortality with tiotropium delivered via the Respimat® inhaler in COPD, particularly in those with cardiovascular disease and arrhythmias, but the data is inconsistent.8-10 
 
December 7, 2015

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Author(s):

  • Arden Barry PharmD ACPR
  • Christina Korownyk MD CCFP

1. Rodrigo GJ, Castro-Rodriguez JA. Chest. 2015; 147:388-96.

2. Santanello NC, Zhang J, Seidenberg B, et al. Eur Respir J. 1999; 14:23-7.

3. Kerstjens HA, Casale TB, Bleecker ER, et al. Lancet Respir Med. 2015; 3:367-76.

4. Tian JW, Cheb JW, Chen R, et al. Respir Care. 2014; 59:654-66.

5. Befekadu E, Onofrei C, Colice GL. J Asthma Allergy. 2014; 7:11-21.

6. Global Initiative for Asthma. Global strategy for asthma management and prevention (2015 update). Available at: www.ginasthma.org. (Last accessed June 19, 2015)

7. Spiriva® Respimat® inhalation solution (2.5 mcg tiotropium per actuation) [product monograph]. Burlington, ON: Boehringer Ingelheim (Canada) Ltd; 2015 May 20.

8. Singh S, Loke YK, Enright PL, et al. BMJ. 2011; 324:d3215.

9. Verhamme KM, Afonso A, Romio S, et al. Eur Respir J. 2013; 42:606-15.

10. Wise RA, Anzueto A, Cotton D, et al. N Engl J Med. 2013; 369:1491-1501.

Authors do not have any conflicts of interest to declare.